Microfluidic systems, devices, and kits for suspension therapy preparation and / or infusion and methods for use

Abstract

Systems, devices, and methods may be deployed to process and / or prepare volumes of suspension therapy for infusion into a patient by, for example, receiving a volume of therapeutic suspension and then processing it to, for example, remove waste, adjust concentration of therapeutic agents suspended in the therapeutic suspension, and / or otherwise prepare the therapeutic suspension for infusion into a patient. The systems, device, and / or methods may use one or more microfluidic devices to process the therapeutic suspension and prepare it for use. When therapeutic agents suspended within the therapeutic suspension are cells, the systems, devices, and / or methods disclosed herein may be deployed as a bioreactor to, for example, feed the cells and / or otherwise maintain viability prior to infusion and / or use.

Description

MICROFLUIDIC SYSTEMS, DEVICES, AND KITS FOR SUSPENSION THERAPY PREPARATION AND / OR INFUSION AND METHODS FOR USERELATED APPLICATIONS

[0001] This application is an INTERNATIONAL (PCT) application claiming priority to United States provisional patent application number 63 / 574,874, Filed 04 April 2024 and entitled “MICROFLUIDIC SYSTEMS AND DEVICES FOR SUSPENSION THERAPY PREPARATION AND / OR INFUSION AND METHODS FOR USE” and United States provisional patent application number 63 / 645,822, filed 10 May 2024 and entitled “MICROFLUIDIC SYSTEMS, DEVICES, AND KITS FOR SUSPENSION THERAPY PREPARATION AND / OR INFUSION AND METHODS FOR USE,” both of which are incorporated by reference in their respective entireties.FIELD OF INVENTION

[0002] This invention is directed to medical devices, medical robotic devices, microfluidic 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 withviruses 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] Microfluidic devices may comprise a substrate with a plurality (e.g., 2-10) of inertial element features positioned therein and / or thereon via, for example, etching, molding, three-dimensional printing, and the like. When a microfluidic device includes two inertial element features, the first inertial feature may include a primary channel with a first end and a second end; a first inlet port positioned proximate to, and in fluid communication with, the first end of the primary channel; a first outlet port positioned proximate to, and in fluid communication with, the second end of the primary channel; a first waste line configured and positioned to allow for extraction of waste from a suspension passing through the first inertial element features; and a first portion of a waste channel. The second inertial element feature may include a secondary channel with a first end and a second end; a second inlet port positioned proximate to, and in fluid communication with, the first end of the secondary channel; a second outlet port positioned proximate to, and in fluid communication with, the second end of the secondary channel; a second waste line configured and positioned to allow for extraction of waste from a suspension passing through the second inertial element features; and a second portion of the waste channel.

[0005] In many embodiments, the first inertial feature may include a plurality of waste subchannels in communication with and extending from the primary channel to the first portion of the waste channel so that waste may be communicated from the primary channel to the first portion of the waste channel. Additionally, or alternatively, the second inertial feature may include a plurality of waste subchannels in communication with and extending from the secondary channel to the second portion of the waste channel so that waste may be communicated from the secondary channel to the second portion of the waste channel

[0006] In some embodiments, the microfluidic device of claiml, wherein at least one of the primary channel and the secondary channel are configured to create aninertial gradient in a volume of therapeutic suspension flowing therethrough that acts to concentrate, or pull, the therapeutic agents toward a center and / or interior edge of the at least one primary channel and secondary channel spiral and push waste media and debris toward an outer edge of the at least one primary channel and secondary channel as the volume of therapeutic suspension moves along the at least one primary channel and secondary channel. For example, the primary and / or second channel(s) may be circular and / or spiral shaped. Additionally, or alternatively, a plurality of waste subchannels extending from the primary channel to the first portion of the waste channel, wherein at least one of the primary channel and the secondary channel are configured to create an inertial gradient in a volume of therapeutic suspension flowing therethrough that acts to concentrate, or pull, the therapeutic agents toward a center and / or interior edge of the at least one primary channel and secondary channel spiral and push waste toward an outer edge of the at least one primary channel and secondary channel as the volume of therapeutic suspension moves along the at least one primary channel and secondary channel, wherein the waste may be drawn into a waste subchannel of the plurality of waste subchannels for evacuation from the microfluidic device via the waste channel.

[0007] In some embodiments, a tube may connect the first outlet port to the second inlet port, thereby enabling fluid communication between the first outlet port to the second inlet port via the tube.

[0008] Additionally, or alternatively, in some embodiments the microfluidic devices disclosed herein may include a cover configured to cover at least a portion of the substrate and / or inertial element feature(s). At times, the cover may have one or more openings configured to allow communication with at least one of the first inlet port, the first outlet port, the second inlet port, the second outlet port, and a waste channel outlet port in communication with the waste channel. This communication may be established via, for example, one or more connectors coupled to the cover that enable fluid communication with a port of the microfluidic device via a tube coupled thereto. For example, the microfluidic device may include a first coupling in communication with the first inlet port; a second coupling in communication with the first outlet port; a third coupling in communication with the second inlet port; a fourth coupling in communication with the second outlet port; and a fifth coupling in communication with a waste channel outlet port. In these embodiments, a tube may connect the second coupling and the third coupling and the tube may be configuredand / or arranged to enable fluid communication between the first outlet port to the second inlet port. Additionally, or alternatively, the first coupling may be configured to communicate a volume of a therapeutic suspension to the first inlet port. Additionally, or alternatively, the fourth coupling may be configured to extract a volume of processed therapeutic suspension from the second outlet port.Additionally, or alternatively, the fifth coupling may be configured to extract a volume of waste from the waste channel outlet port.

[0009] Additionally, or alternatively, a cover may have one or more openings configured to allow communication with at least one of the first inlet port, the first outlet port, the second inlet port, the second outlet port, and a waste channel outlet port in communication with the waste channel, wherein the first, second, third, fourth, and fifth couplings are physically coupled to, and extend from, the cover.

[0010] In some embodiments, the microfluidic device may include a third inertial element feature positioned on and / or in the substrate. The third inertial feature may include a third channel with a first end and a second end; a third inlet port positioned proximate to, and in fluid communication with, the first end of the third channel; a third outlet port positioned proximate to, and in fluid communication with, the second end of the third channel; a third waste line configured and positioned to allow for extraction of waste from a suspension passing through the third inertial element features; and a third portion of the waste channel. In these embodiments, a tube connecting the second outlet port to the third inlet port, the tube enabling fluid communication between the second outlet port to the third inlet port.

[0011]

[0012] The systems disclosed herein may be configured to process a therapeutic suspension using one or more of the therapeutic devices disclosed herein. Processing of a therapeutic suspension may include, but is not limited to, washing, concentrating, feeding, conditioning, magnetizing (via, for example, introduction of magnetic beads configured to bond to therapeutic agents of a therapeutic suspension) and / or cleaning (e.g., waste removal) the therapeutic suspension and / or therapeutic agents suspended therein. In some embodiments, a plurality of microfluidic devices may be connected in series with one another so that an outlet port of a first microfluidic device of the plurality of microfluidic devices may be in communication with an inlet port of a second microfluidic device of the plurality of microfluidic devices. Additionally, or alternatively, a plurality of microfluidicdevices may be connected in parallel to one another so that each microfluidic device of the plurality of microfluidic devices an outlet port of a first microfluidic device of the plurality of microfluidic devices may be in communication with an inlet port of a second microfluidic device of the plurality of microfluidic devices.

[0013] Additionally, or alternatively, the systems disclosed herein may include one or more microfluidic devices, a processing device and / or base unit including a first, second, third, and fourth valve; a first container configured to hold a volume of the therapeutic suspension, the first container being in communication with the processing device via a first tube coupled first container and the processing device, the first tube being in communication with the first valve; a second container configured to hold a volume of wash media, the second container being in communication with the processing device via a second tube coupled second container and the processing device, the second tube being in communication with the second valve; a third container configured to hold a volume of waste, the third container being in communication with the processing device via a third tube coupled third container and the processing device, the third tube being in communication with the third valve; and a fourth container configured to hold a volume of processed therapeutic suspension, the fourth container being in communication with the processing device via a fourth tube coupled fourth container and the processing device, the fourth tube being in communication with the fourth valve, wherein communication between the first, second, third, and fourth containers may be controlled by the processing device. Communication between the first, second, third, and fourth containers may be controlled by the processing device when it opens and / or closes one or more of the first, second, third, and / or fourth valves, respectively.

[0014] In some embodiments, the first container may be a syringe that includes a barrel that holds the volume of the therapeutic suspension and a plunger in communication with the barrel, wherein the volume of the therapeutic suspension enters the first tube when the plunger may be pushed into the barrel. At times, the syringe may be a self-sterilizing syringe.

[0015]

[0016] In some embodiments, the processing device may be configured to open the first valve so that a portion of the volume of therapeutic suspension may be communicated to the first inlet port of the microfluidic device. Additionally, oralternatively, the processing device may further include a fifth valve and a cell culture media container configured to hold a volume of cell culture media infusion media, the cell culture media container being in communication with the processing device via a fifth tube coupled cell culture media container and the processing device, the fifth tube being in communication with the fifth valve. Additionally, or alternatively, the processing device may include another valve an infusion media container configured to hold a volume of infusion media infusion media, the infusion media container being in communication with the processing device via a sixth tube coupled infusion media container and the processing device, the sixth tube being in communication with the other valve.

[0017] In some instances, processing device may be configured to open the first valve so that a portion of the volume of therapeutic suspension may be communicated to the filter and waste media that flows through the filter may be communicated to the third container. In some embodiments, the system may further comprise a filter configured to capture therapeutic agents suspended in the volume of therapeutic suspension and allow waste to flow therethrough. Additionally, or alternatively, the processing device may be configured to open the first valve so that a portion of the volume of therapeutic suspension may be communicated to the filter and therapeutic agents captured by the filter may be communicated to the fourth container. The filter may be, for example, a nano filter, a magnetic filter system, a hydrodynamic focusing device, hydrodynamic focusing trap, a deterministic lateral displacement device, and a viscoelastic microfluidic concentrator.BRIEF DESCRIPTION OF DRAWINGS

[0018] The present invention is illustrated by way of example, and not limitation, in the figures of the accompanying drawings in which:

[0019] FIG. 1A is a block diagram of a top view of an exemplary microfluidic device, in accordance with some embodiments of the present invention.

[0020] FIG. 1 B is schematic a diagram of a top view of an exemplary cover for the microfluidic device of FIG. 1 A, in accordance with some embodiments of the present invention.

[0021] FIG. 1C is a schematic diagram of a side view of an assembly of the cover of FIG. 1 B and the microfluidic device of FIG. 1A, in accordance with some embodiments of the present invention.

[0022] FIG. 2A is a schematic diagram of a top perspective view of another exemplary microfluidic device, in accordance with some embodiments of the present invention.

[0023] FIG. 2B is a schematic diagram of a bottom view of the microfluidic device of FIG. 2A, in accordance with some embodiments of the present invention.

[0024] FIG. 2C is a schematic diagram of a detailed view of a portion microfluidic device of FIG. 2A, in accordance with some embodiments of the present invention.

[0025] FIG. 3A is a schematic diagram of a top view of an assembly including the microfluidic device of FIG. 2A, a cover, and a plurality of connectors, in accordance with some embodiments of the present invention.

[0026] FIG. 3B is a schematic diagram of a side perspective view of the assembly of FIG. 3A, in accordance with some embodiments of the present invention.

[0027] FIG. 3C is a schematic diagram of a side perspective view of the assembly of FIG. 3A with a catheter attached thereto, in accordance with some embodiments of the present invention.

[0028] FIG. 4A is a schematic diagram of a top view of exemplary microfluidic device with six inertial element features, in accordance with some embodiments of the present invention.

[0029] FIG. 4B is a schematic diagram of a top view of exemplary microfluidic device with three inertial element features, in accordance with some embodiments of the present invention.

[0030] FIG. 5A is a schematic diagram of an array of assemblies like the assemblies shown in FIG. 3, in accordance with some embodiments of the present invention.

[0031] FIG. 5B is a schematic diagram of a top perspective view of a parallel array of microfluidic devices, in accordance with some embodiments of the present invention.

[0032] FIG. 6A is a schematic diagram of an exemplary kit that may be used to execute with one or more systems or devices disclosed herein to, for example, execute one or more methods disclosed herein.

[0033] FIG. 6B is a schematic diagram of a detailed view of a portion of the kit shown in FIG. 6A, in accordance with some embodiments of the present invention.

[0034] FIG. 7 is a block diagram of an exemplary hydrodynamic focusing device and / or trap that may be employed with and / or communicatively coupled to a microfluidic device, in accordance with some embodiments of the present invention.

[0035] FIG. 8 is a schematic diagram of an exemplary microfluidic device that utilizes deterministic lateral displacement to process therapeutic media and / or generate concentrated therapeutic media, in accordance with some embodiments of the present invention.

[0036] FIG. 9 is a schematic diagram of a microfluidic device that includes a viscoelastic microfluidic concentrator that directs cells into a concentrated area, or region, of microfluidic device via the therapeutic media’s viscoelastic properties, in accordance with some embodiments of the present invention.

[0037] FIG. 10 is a block diagram of an exemplary components that may be included in a suspension therapy preparation and infusion system, in accordance with some embodiments of the present invention.

[0038] FIG. 11 is a block diagram of an exemplary suspension therapy preparation and infusion system, in accordance with some embodiments of the present invention.

[0039] FIG. 12 is a schematic diagram of a top view of an exemplary base unit, in accordance with some embodiments of the present invention.

[0040] FIG. 13A is a schematic diagram of a top view of an exemplary scaffold for use with, for example, the systems of FIGs. 11 and / or 12, in accordance with some embodiments of the present invention.

[0041] FIG. 13B is a schematic diagram of a top view of an exemplary scaffold for use with, for example, the systems of FIGs. 11 and / or 12, in accordance with some embodiments of the present invention.

[0042] FIG. 13C is a schematic diagram of a top view of an exemplary scaffold for use with, for example, the systems of FIGs. 11 and / or 12, in accordance with some embodiments of the present invention.

[0043] FIG. 13D is a schematic diagram of a side view of the exemplary scaffold of FIGs. 13A, 13B, and / or 13C, in accordance with some embodiments of the present invention.

[0044] FIG. 14 is a schematic diagram of an assembly of the base unit of FIG. 12 and the scaffold of FIG. 13A, 13B, or 13C, in accordance with some embodiments of the present invention.

[0045] FIG. 15 is a block diagram of an exemplary fluid communication path through the system of FIGs. 11, 12, and / or 13, in accordance with some embodiments of the present invention.

[0046] FIG. 16 is a schematic diagram of a perspective view of a system including a base unit and an array of microfluidic devices, in accordance with some embodiments of the present invention.

[0047] FIG. 17A is an image of a top of a nano filter, in accordance with some embodiments of the present invention.

[0048] FIG. 17B is an image of a cross-section of a nano filter, in accordance with some embodiments of the present invention.

[0049] FIG. 17C is an image of a perspective of a nano filter following use, in accordance with some embodiments of the present invention.

[0050] FIG. 17D is a schematic diagram of a system for processing and / or concentrating therapeutic media including a nano filter, in accordance with some embodiments of the present invention.

[0051] FIG. 18 is a schematic diagram of a magnetic separation system, in accordance with some embodiments of the present invention.

[0052] FIG. 19 is a flowchart illustrating an exemplary process for processing a therapeutic suspension and / or infusing a therapeutic suspension into a patient, in accordance with some embodiments of the present invention.

[0053] FIG. 20 is an illustration of screen shot of an exemplary graphic user interface, in accordance with some embodiments of the present invention.

[0054] FIG. 21 is a block diagram of an exemplary self-sterilizing syringe, in accordance with some embodiments of the present invention.

[0055] 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

[0056] The present invention is directed to, among other things, systems, devices, and methods for atraumatically preparing and delivering volumes of a 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. In some embodiments and / or use cases of the systems, devices, and / or methods disclosed herein may be used and / or adapted for use to process relatively large volumes of therapeutic suspension when, for example, preparing a relatively large volume of therapeutic suspension for infusion into a patient and / or manufacturing or culturing therapeutic suspension and / or therapeutic agents for inclusion in a therapeutic suspension. On some occasions, some of the systems, devices, and / or components thereof may be used multiple times to iteratively, serially, and / or successively process a therapeutic suspension.

[0057] 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. 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.

[0058] 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. 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 (patientready therapeutic suspension”). This multi-step preparation process may include thawing the original therapeutic suspension, filtering, separating, and / or washing the therapeutic agents (e.g., separation of therapeutic cells and / or therapeutic particles from their original media), resuspending the therapeutic agents in new media (e.g., blood, reagents, hydrogel, 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 therapeutic agent and / or cell viability, count, and / or functionality and can potentially compromise treatment efficacy and / or lead to improper (e.g., insufficient or excess) dosing of therapeutic agents delivered to a patient.

[0059] The systems, devices, methods and / or components thereof disclosed herein may be used as, for example, a bioreactor to incubate, culture, manufacture, and / or sustain viability for biological therapeutic agents such as cells, viruses, DNA,

[0060] Disclosed herein are therapeutic agent separation devices that 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 arrangedwithin the microfluidic device to facilitate hydrodynamic and / or inertial focusing of therapeutic suspension and / or therapeutic agents within the 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 (also referred to herein as “waste channels” of “waste subchannels”, thereby separating the liquid from the therapeutic agents so that a concentration of therapeutic agents within the therapeutic suspension increases as it travels along the channel and waste is drawn away from it. Additionally, or alternatively, a channel diameter may be sized, shaped, and / or configured with one or more inertial element features (e.g., spirals, curves, etc.) that facilitate inertial focusing of the therapeutic suspension so that as the therapeutic suspension travels along the inertial element features, 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 from the therapeutic suspension, given that those elements may be lighter in weight than whole cells and thus can be directed to flow out of the device along with the bulk of the therapeutic suspension that does not include therapeutic agents.

[0061] In some embodiments, the microfluidic devices 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 therapeutic agents (e.g., cell counting) on the diverted sample and / or perform one or more quality control measurements / assessments on the diverted sample to, for example, determine a count, strength, 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 1040 according to, for example, one or more instructions received from memory 1042 and / or user interface device 1025 of system 1000 in, for example, an automated, semi-automated, and / or manual fashion.

[0062] In some embodiments, counting of therapeutic agents in the form of cells may be performed using an impedance-based counter, which may be deployed as, for example, an inline channel and / or chamber through which a small volume (e.g., 0.001-0.01% of overall therapeutic media volume) of therapeutic media passes and, as the cells pass through the channel and / or chamber, a disruption (e.g., impedance) in electrical flow may be measured as the cells pass through.Advantages to using an impedance-based counter include, but are not limited to, greater accuracy and / or providing an ability to dynamically count cells as they flow through the channel and / or chamber.

[0063] In some embodiments, the microfluidic devices disclosed herein may also include a flush port and chamber configured to accept entry of fresh media into respective microfluidic device that may be used to, for example, dislodge a number of therapeutic agents adhered to, or otherwise captured by the microfluidic device or a component coupled there to (e.g., a leur connection) 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.

[0064] Additionally, or alternatively, the microfluidic devices disclosed herein may incorporate a microfluidic bubble trap device designed to efficiently capture and remove gas bubbles within a flowing liquid. The microfluidic bubble trap device may comprise 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 may be 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 concentratetoward a designated area of the channel, allowing for their separation from the liquid and preventing interference with downstream processes.

[0065] The inertial element features described herein may be configured to direct the flow of fluid through a microfluidic device in a desired manner. The inertial element features described herein include channels that have a spiral, linear, and / or curved shape. At times, the inertial element features described herein may be referred to as “inertial element features”.

[0066] One or more aspects (e.g., spiral curvature characteristics, channel diameter, channel curvature, channel shape, etc.) of a microfluidic device disclosed herein and / or a component thereof (e.g., inertial element features and / or port into and / or out of an inertial element features) may be sized, shaped, selected, and / or otherwise configured to account for one or more properties of fluid and / or or microfluid dynamics including, but not limited to, the Bernoulli principle, resistance, and / or Dean number so that, for example, focusing of therapeutic agents within a channel of an inertial element features, and / or a type of flow (e.g., laminar or turbulent) through an inertial element features may be optimized for one or more of features including, but not limited to tolerance for therapeutic agent loss due to processing (e.g., the drawing off of waste, the separation of therapeutic agents from waste), efficiency of process, likelihood of adhesion of therapeutic agents to inertial element features components, therapeutic suspension viscosity, therapeutic agent type, size, shape, and / or other therapeutic agent or therapeutic suspension characteristics including but not limited to decay rate, temperature requirements, tendency to clump together, cell type, cell shape, cell viability, cell concentration, volume of therapeutic suspension to be processed, time available to process the therapeutic suspension, and / or sensitivity to shear stress, pressure, and / or force exerted on the therapeutic agents as they travel through the inertial element features(s).

[0067] For microfluidic devices with a plurality of inertial element features, an internal diameter and / or cross-sectional area of a channel (often a spiral-shaped channel) for each inertial element features of the microfluidic device may be the same or may vary. For example, in many cases, an internal diameter and / or cross- sectional area of a channel of a first (or first used) inertial element features may be larger than an internal diameter and / or cross-sectional area of a channel of a second, or subsequently used, inertial element features. This reduction in the internal diameter and / or cross-sectional area of a channel of a second-used inertialelement features compared with a first-used inertial element features may be configured to capitalize on fluid dynamic principles (e.g., the Bernoulli principle), wherein a reduced cross-sectional area of the second-used inertial element features channel may act to maintain a speed, or velocity, of the therapeutic suspension traveling through it.

[0068] Relative dimensions may be configured and / or selected to accommodate cell type, cell dimensions, cell geometry, cellular tolerance to shear stress, cellular tolerance to forces, and so on. For example, an inertial element features configured to process relatively small cells (e.g., blood and T-cells) may include a channel with a relatively small diameter while an inertial element features configured to process relatively large and / or irregularly shaped cells (e.g., neurons or theta pancreatic cells) may include a channel with a relatively large diameter.

[0069] In some embodiments, the systems, devices, and methods disclosed herein may be used to process relatively large volumes of therapeutic suspension by, for example, using relatively large bags or containers for wash media, waste, therapeutic suspension, etc. and / or by using (simultaneously or otherwise) multiple microfluidic devices in series and / or in parallel.

[0070] Additionally, or alternatively, the systems, devices, and methods disclosed herein may be used to create, prepare, and / or dispense highly- concentrated therapeutic media for use with and / or in, for example, compartmentalized, delicate, and / or sensitive tissue, such as the brain and / or eye. Exemplary concentration ranges for highly-concentrated therapeutic media include, but are not limited to, 0.9-1 ,2million therapeutic agents per microliter, 1 -1.15million therapeutic agents per microliter, or 0.75-1 ,4million therapeutic agents per microliter. At times, the highly-concentrated therapeutic media may have a relatively high viscosity. Once prepared, the highly-concentrated therapeutic media may be delivered to a patient interface device such as a delivery syringe and / or catheter.

[0071] In some cases, the systems, devices, and / or methods may incorporate one or more microfluidic routing plate(s) configured to control a pathway for and / or direct a flow of, for example, therapeutic media, concentrated therapeutic media, and / or waste. The microfluidic routing plate(s) may include, for example, one or more devices (e.g., valves, couplings, and / or channels) that may be used in addition and / or alternatively to other microfluidic features disclosed herein to, for example,divert fluid (e.g., therapeutic media and / or waste) to various locations in a system and / or device (e.g., a microfluidic chip, chamber, or via).

[0072] For example, in some embodiments, one or more microfluidic routing plate(s) may be incorporated into the systems and / or devices disclosed herein using a mechanical and / or fluid coupling such as a luer-based manifold and / or barbed fitting. Additionally, or alternatively, one or more microfluidic routing plate(s) may be directly incorporated into one or more microfluidic chips, microfluidic devices, and / or microfluidic plates (a device incorporating two more microfluidic devices) of the systems and / or devices disclosed herein, which may reduce dead volume caused by, for example, couplings (e.g., luer couplings), valves (e.g., pinch valves) and / or reduce a length of tubing and / or number of external connections required to move therapeutic media and / or waste from point to point in the systems and / or devices disclosed herein.

[0073] Turning now to the figures, FIG. 1 A is a block diagram of an exemplary microfluidic device 100 that may be included in, and / or cooperate with, a therapeutic agent separation device and / or one or more of the systems and / or base units disclosed herein. Microfluidic device 100 may include a substrate 150 with an inlet port 105, a waste outlet port 110, a concentrated therapeutic agents outlet port 115, a primary channel 120, a plurality of waste sub-channels 125, a waste channel 130, a concentrated therapeutic agents channel 135, and a resistive element 140. During use, a volume of therapeutic suspension may enter microfluidic device 100 via inlet port 105 and may travel along primary channel 120 until it reaches a separation point 122. In the embodiment of FIG. 1A, primary channel 120 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 122, 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 channels 125 for collection in waste channel 130 and, as it travels along waste channel 130, it may exit microfluidic device 100 via waste outlet port 110. As the inertially separated volume of therapeutic suspension arrives at separation point 122 a portion of the volume of therapeutic suspension with a greater concentration of therapeutic agents continues to travel in a spiral path along concentrated therapeuticagents channel 135. As the portion of the volume of therapeutic suspension with a greater concentration of therapeutic agents travels along concentrated therapeutic agents channel 135, it continues to be inertially separated from waste, which is drawn off into outlet subchannel 125 until the portion of the volume of therapeutic suspension with a greater concentration of therapeutic agents reaches resistor 192, 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 135, it may exit microfluidic device 100 via concentrated therapeutic agents outlet port 115. In some embodiments, a portion and / or a surface of side of one or more of primary channel 120, plurality of waste sub-channels 125, waste channel 130, concentrated therapeutic agents channel 135 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.).

[0074] Optionally, in some embodiments, microfluidic device 100 may include a quality control chamber 137 that may be in liquid communication with concentrated therapeutic agents channel 135 via a quality control channel 133. A relatively small sample of the volume of concentrated therapeutic suspension may flow into quality control channel 133 and pool in quality control chamber 137. 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 a viability and / or sterility assessment module.

[0075] Optionally, in some embodiments, microfluidic device 100 may include a flush inlet 147 coupled to concentrated therapeutic agents channel 135 via a flush channel 143. Flush inlet 147 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 135 into, for example, concentrated therapeutic agents outlet port 115 so that therapeutic agents that may remain within concentrated therapeutic agents channel 135 may be evacuated and / or washed therefrom.

[0076] FIG. 1 B is a diagram of an exemplary cover 101 for microfluidic device 100 that includes a cover body 151 with an inlet port connector 106, a waste outlet port connector 111 , a concentrated therapeutic agents port connector 116. Connectors 106, 111 , and / or 116 may be, for example, luer or other connectors adapted to couple one or more tubes and / or devices disclosed herein to cover body 151 so that volume of therapeutic suspension may be added to microfluidic device 100 via a coupling between inlet port connector 106 and inlet port 105; waste may be extracted from microfluidic device 100 via a coupling between waste port 110 and waste port coupling 111 ; and concentrated therapeutic agents may be extracted from microfluidic device 100 via a coupling between concentrated therapeutic agents outlet port 115 and concentrated therapeutic agents outlet port connector 116. In many cases, cover 101 may fit over and / or cover all and / or a portion of microfluidic device 100 as shown in the assembly 106 of FIG. 1C.

[0077] In some embodiments, for microfluidic device 100 and / or cover 101 may be configured to cooperate with a therapeutic agent collection device and / or container such as therapeutic agent collection device 160, which is also shown in FIG. 1 B. When in use, therapeutic agent collection device 106 may be configured to couple to concentrated therapeutic agents outlet port 115 via concentrated therapeutic agents outlet port connector 116 (e.g., screw and / or clamp on) and collect a volume of concentrated therapeutic agents that flows from concentrated therapeutic agents outlet port 115. Once the volume of therapeutic suspension is fully separated by microfluidic device 100 (i.e., there is none left to separate) and / or therapeutic agent collection device 160 is full, the volume of concentrated therapeutic agents may be removed from therapeutic agent collection device 160 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 160 for a desired length of time. Additionally, or alternatively, the volume of concentrated therapeutic agents may be housed in therapeutic agent collection device 160 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 160 may be embodied as a small distensible bag in communication withconcentrated therapeutic agents outlet port connector 116 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 disclosed herein. This process may be assisted by rinsing and / or washing the therapeutic agent collection device 160 with, for example, wash media, to remove any therapeutic agents that may remain in therapeutic agent collection device 160 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.

[0078] In some embodiments, cover 101 may include a flush coupling 149 sized, shaped, and / or configured to be flush inlet 147 so that flush media may be introduced to flush inlet 147. Additionally, or alternatively, cover 101 may include a quality control coupling and / or cover 139 configured to cooperate with quality control chamber 137 and, in some cases, enable imaging and / or processing of therapeutic agents held within quality control chamber 137. This may be accomplished when, for example, quality control coupling and / or cover 139 is transparent and allows for imaging of the therapeutic agents held in quality control chamber 137. In some cases, a lower surface of quality control chamber 137 may also be transparent so that, for example, a light may be positioned beneath quality control chamber 137 and a camera, microscope, or other imaging device may be positioned on top of quality control coupling and / or cover 139 so that it may image the lit therapeutic agents held in quality control chamber 137 and / or perform one or more quality control checks thereon.

[0079] 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 qualitycontrol 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.

[0080] At times, when waste is pulled away from a volume of the therapeutic suspension flowing through a microfluidic device, or component thereof, such as the inertial element features described herein, the pulling of the waste away from the volume of therapeutic suspension may cause turbulence, or other disruptions, in the flow of the therapeutic suspension as it travels through the inertial element features. These flow disruptions may result in a defocusing of the therapeutic agents flowing through the inertial element features and, consequently, some (e.g., 5-50%) of the therapeutic agents may be undesirably pulled into a waste subchannel because they are proximate to a junction between the inertial element features and the waste subchannel instead of being focused, or concentrated, toward the inner edge of the inertial element features. To combat this outcome while keeping shear stress and other stresses on the therapeutic suspension and / or therapeutic agents included therein within limits that preserve viability, a microfluidic device may include a plurality (e.g., 2-16) inertial element features that may be used in series and / or parallel to sequentially and / or progressively increase a concentration of therapeutic agents within a volume of therapeutic suspension and / or sequentially and / or progressively remove waste from an initial volume of therapeutic suspension with an output of the microfluidic device being a highly concentrated volume of therapeutic suspension that includes little (e.g., 0.1-10%), or no, waste material.

[0081] FIG. 2A is a schematic diagram of a perspective view of an exemplary dual-inertial-element-feature microfluidic device 200 (also referred to herein as “microfluidic device 200”) that may be included in, and / or cooperate with, for example, a therapeutic agent separation device and / or one or more of the systemsand / or base units disclosed herein. FIG. 2B is a back view of microfluidic device 200 with substrate 201 being clear and / or transparent so that features of microfluidic device 200 may be seen.

[0082] Microfluidic device 200 includes a substrate 201 with a first inertial element feature 202 and a second inertial element feature 203 positioned therein and / or thereon. In some embodiments, an outlet port 215 of first inertial element feature 202 may be connected to an inlet port 207 of second inertial element feature 203 via a first tube 250 as shown in FIGs. 2A and 6B. First inertial element feature 202 includes inlet port 205, outlet port 215, a primary channel 220 that is spiral shaped, a plurality of waste subchannels 225 in fluid communication with primary channel 220 and a first portion of a waste channel 230.

[0083] Second inertial element feature 203 includes inlet port 207, outlet port 217, a secondary channel 222 that is spiral shaped, a concentrated therapeutic agents channel 235, and a plurality of waste subchannels 225 in fluid communication with secondary channel 222 and a second portion of a waste channel 230. First and second portions of waste channel 230 are connected to one another forming a single waste channel 230 from which a waste port 225 extends. In some embodiments, a portion and / or a surface of side of one or more features of microfluidic device 200 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.).

[0084] In the embodiment of FIG. 2A, primary channel 220 and secondary channel 222 are spiral shaped so that they create an inertial gradient in the volume of therapeutic suspension flowing therethrough that acts to concentrate, or pull, the therapeutic agents (e.g., cells) toward a center, and / or interior edge, of the spiral and push waste media and debris toward an outer edge of the spiral as the volume of therapeutic suspension moves along primary and secondary channels 220 and 222. Thus, in one embodiment, when a volume of a therapeutic suspension enters (e.g., is pumped in using a syringe pump or other pump) primary channel 220 via inlet port 205 and begins to travel around primary channel 220, it becomes inertially separated so that therapeutic agents suspended in the therapeutic suspension are pulled toward the interior edge of primary channel 220 and waste media and debris are pushed to an exterior edge of primary channel 220. When the inertially separatedvolume of therapeutic suspension reaches a junction between primary channel 220 and a waste subchannel 225, an inertially separated portion of the volume of therapeutic suspension (e.g., waste media, debris, etc.) may be split of into one or more waste subchannel 225 for collection in waste channel 230 and eventual exit from microfluidic device 200 via waste outlet port 210 while a portion of the volume of therapeutic suspension with a greater concentration of therapeutic agents may continue to travel in the spiral path of primary channels 220 until it eventually reaches outlet port 215 for extraction and transfer to secondary channel 222 via first tube 250. As the portion of the volume of concentrated therapeutic suspension travels along secondary channel 222, therapeutic agents therein continue to be inertially separated from waste, which is drawn off into waste sub-channels 225 until the volume of concentrated therapeutic suspension reaches outlet port 217 and may be extracted from microfluidics device 200 for further processing and / or infusion into a patient as, for example, described herein.

[0085] Optionally, in some embodiments, microfluidic device 200 may include a quality control chamber (not shown) like quality control chamber 137 that may be in liquid communication with one or more features of microfluidic device 200. In these embodiments, a relatively small sample of the volume of concentrated therapeutic suspension may flow into the quality control channel and pool in quality control chamber for further analysis and / or performance of one or more quality control measurements. 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 a viability and / or sterility assessment module.

[0086] Optionally, in some embodiments, microfluidic device 200 may include a flush inlet (not shown) that may be coupled to, for example, primary and / or secondary channel(s) 220 and / or 222. The flush inlet may be configured to allow for introduction of wash media or other fluid (e.g., saline) into one or more features of microfluidic device 200 to, for example, flush therapeutic agents therefrom into, for example, concentrated therapeutic agents port 215 so that therapeutic agents that may unintentionally remain within a feature of microfluidic device 200 may be evacuated and / or washed therefrom.

[0087] At times, one or more of the microfluidic devices disclosed herein may include one or more secondary, or focusing, outlet channels positioned along an edge, or side, of an inertial feature opposite that of a waste sub-channel (e.g., .waste sub-channel(s) 125 and / or 225). Secondary outlet channels may be sized, positioned, and / or configured to pull therapeutic agents traveling through an inertial element feature via a therapeutic suspension into a preferred position (e.g., proximate to an internal edge) within a channel of the inertial element features following disruption and / or turbulence that may be caused by waste media being pulled into one or more of the waste sub-channels (e.g., waste sub-channel 125 and / or 225) and / or waste channels (e.g., waste channels 130 and / or 230). One example of a microfluidic device that includes secondary, or focusing, channels 260 is shown in the close up view of inertial element feature 202 of FIG. 2C with a joint between each secondary outlet channel 260 being encircled in red. Secondary outlet channels 260 are positioned on an internal edge of the main channel of inertial element feature 202 proximate to primary waste outlets so that they may focus therapeutic agents into a preferred location within the main channel of inertial element feature 202 after potentially experiencing the introduction of turbulence caused via waste from the flow of therapeutic suspension being drawn off into a waste sub-channel 225.

[0088] FIG. 3A is a schematic diagram of a top view and FIG. 3B is a perspective view of an assembly 300 of microfluidic device 200, a cover 305, and a plurality of connectors and / or couplings 310, wherein a first coupling 310A may facilitate fluid communication with inlet port 205, a second coupling 310B may facilitate fluid communication with outlet port 215, a third coupling 310C may facilitate fluid communication with waste outlet port 210, a fourth coupling 310D may facilitate fluid communication with inlet 207, and fifth coupling 310E may facilitate fluid communication with outlet port 217. First-fifth coupling 310A-310E may be any coupling or device that is configured to couple to a tube or other device (e.g., canister, vial, pump, etc.) that is carrying a volume of, for example, gas (e.g., air oxygen, or carbon dioxide), therapeutic suspension, waste media, and / or fresh media, nutrients. Exemplary couplings 310 may be, for example, leur couplings, friction couplings, and / or clamps configured to securely couple a tube or device thereto and hold it in place. At times, one or more couplings 310 may be removably attached to cover 305.

[0089] At times, a limitation, or disadvantage to using the inertial focusing provided by microfluidic devices like microfluidic device 200 and / or assembly 300 to achieve high concentration of therapeutic agents in a therapeutic suspension is that as the viscous, highly concentrated, therapeutic suspension that travels along waste sub-channel 225 and / or exits outlet port 215, it changes the resistance balance within microfluidic device 200 and / or at outlet port 215. In some embodiments, waste outlet port 210 and / or third coupling 310C may be attached to (and in the case of third coupling 310C, may be) an adjustable resistance mechanism (e.g., a valve) that controls a flow (e.g., volume and / or velocity) of waste exiting waste outlet port 210. In this way, microfluidic device 200 and / or assembly 300 may be configured as an inertial focusing system with dynamic system control activated and / or regulated by the adjustable resistance mechanism, wherein a flow rate and / or volume of waste exiting microfluidic device 200 and / or assembly 300 acts to adjust and / or regulate the resistance within microfluidic device 200 and / or assembly 300, which may allow for and / or enable achieving high concentrations of therapeutic agents within the output, or concentrated, therapeutic media.

[0090] FIG. 3C is a schematic diagram of a side perspective view of assembly 300 with a connector 325 that couples a catheter 320 to an outlet port for concentrated therapeutic media (the port is not shown) generated by an upper (as oriented in FIG. 3C) inertial element features of assembly 300. In addition, outlet port 310E may be an outlet port for concentrated therapeutic media generated via the inertial element features on the lower portion (as oriented in FIG. 3C) of assembly 300. At times, catheter 320 may be a delivery catheter, which enables a distal end of the delivery catheter to be directly coupled to microfluidic device 200 and / or assembly 300 so that the concentrated and / or processed therapeutic media may be delivered directly to the patient. This increases the efficacy (e.g., time, supplies, etc.) of therapeutic media delivery by eliminating the need for intervening equipment (e.g., syringe or cannister) used to couple microfluidic device 200 and / or assembly 300 to the patient. Additionally, or alternatively, catheter 320 may be coupled to other devices such as a microcentrifuge, bioreactor, and / or temperature- regulated canister to prepare and / or store the concentrated / processed therapeutic media until ready for use.

[0091] FIG. 4A provides a schematic diagram of an exemplary microfluidic device 401 that includes six spirally shaped inertial element features that areconfigured to be used in series to generate a volume of concentrated therapeutic suspension. Initially, a volume of therapeutic suspension is added (e.g., pumped into) a first inertial element features 401 via an inlet port 410. The volume of therapeutic suspension may then travel along first inertial element features 401, which may act to inertially separate particles of therapeutic agents from the volume of therapeutic suspension so that a volume of waste media may be pulled off into a primary waste channel 430 via a first waste subchannel 425 and a volume of first concentrated therapeutic suspension may transfer to a second inertial element features 402 via a first connection channel 411 . The volume of first concentrated therapeutic suspension may travel through a second inertial element features 402, thereby generating a volume of a second concentrated therapeutic suspension (which may be more concentrated than the volume of the first concentrated therapeutic suspension) and a volume of waste material may be drawn off into primary waste channel 430 via a second waste subchannel 425.

[0092] A volume of the second concentrated therapeutic suspension may transfer to a third inertial element features 403 via a second connection channel 412. The volume of second concentrated therapeutic suspension may then travel through third inertial element features 403, thereby generating a volume of a third concentrated therapeutic suspension (which may be more concentrated than the volume of the second concentrated therapeutic suspension) and a volume of waste material may be drawn off into primary waste channel 430 via a third waste subchannel 425.

[0093] A volume of the third concentrated therapeutic suspension may transfer to a fourth inertial element features 404 via a third connection channel 413. The volume of third concentrated therapeutic suspension may then travel through fourth inertial element features 404, thereby generating a volume of a fourth concentrated therapeutic suspension (which may be more concentrated than the volume of the third concentrated therapeutic suspension) and a volume of waste material may be drawn off into primary waste channel 430 via a fourth waste subchannel 425.

[0094] A volume of the fourth concentrated therapeutic suspension may transfer to a fifth inertial element features 405 via a fourth connection channel 414. The volume of fourth concentrated therapeutic suspension may then travel through fifth inertial element features 405, thereby generating a volume of a fifthconcentrated therapeutic suspension (which may be more concentrated than the volume of the fourth concentrated therapeutic suspension) and a volume of waste material may be drawn off into primary waste channel 430 via a fifth waste subchannel 425.

[0095] A volume of the fifth concentrated therapeutic suspension may transfer to a sixth inertial element features 406 via a fifth connection channel 415. The volume of fifth concentrated therapeutic suspension may then travel through sixth inertial element features 406, thereby generating a volume of a sixth, and final concentrated therapeutic suspension (which may be more concentrated than the volume of the fifth concentrated therapeutic suspension) and a volume of waste material may be drawn off into primary waste channel 430 via a fifth waste subchannel 425. A volume of the sixth concentrated therapeutic suspension may be drawn away and / or extracted from sixth inertial element features 406 via an outlet port 416. The volume of the sixth concentrated therapeutic suspension may then be further processed and / or may be infused into a patient.

[0096] FIG. 4B provides a schematic diagram of an exemplary microfluidic device 402 that includes three spirally shaped inertial element features that are configured to be used in parallel to generate a volume of concentrated therapeutic suspension as, for example, described herein.

[0097] Microfluidic device 400 includes a substrate 450 in which a first inertial element features 451 , a second inertial element features 452, and a third inertial element features 453 reside (e.g., are etched into and / or are printed onto). First, second, and third inertial element features 451, 452, and 453 include a respective first, second, and third primary channel 470A, 470B, and 470C, a respective first, second, and third inlet 455A, 455B, and 455C, a respective first, second, and third waste channel 480A, 480B, and 480C and a plurality of waste sub-channels 456 that act to pull waste away from first, second, and third primary channel 470A, 470B, and 470C and into first, second, and third waste channel 480A, 480B, and 480C.

[0098] First, second, and third waste channels 480A, 480B, and 480C form one long channel that terminates at a waste exit port 482 by which waste may exit microfluidic device 400. First, second, and third primary channels 470A, 470B, and 470C are in fluid communication with an arm of a three-armed output channel 475, which is in fluid communication with each of first, second, and third primary channel 470A, 470B, and 470C. Three-armed output channel 475 is also in fluidcommunication with an outlet port 485 by which concentrated and / or processed therapeutic suspension may exit microfluidic device 400. The configuration of microfluidic chip 402 and of three-armed output channel 475 may reduce the number of connections to inertial element features (i.e., one instead of three) and / or reduce the overall dead volume of tubing needed to extract concentrated / processed therapeutic media from microfluidic device 402.

[0099] The design and configuration of microfluidic device 402 enables the simultaneous and / or sequential processing (e.g., concentration) of therapeutic media via the three spirally shaped inertial element features, thereby increasing throughput and reducing the time to process / concentrate therapeutic media while maintaining consistent pressure and / or shear stress on the therapeutic media and / or agents within the therapeutic media as they travel through the inertial element features and exit microfluidic device 402.[000100] In some embodiments, a microfluidic device design may incorporate a plurality of more than two inertial element features that may be used in series and / or in parallel to filter therapeutic agents from media and / or generate a volume of concentrated therapeutic suspension in a manner that may be similar to that used with microfluidic device 200. For example, FIG. 5A is a schematic diagram of a top perspective view of an array 501 of assemblies 300 arranged in a series so that they may, in some embodiments, be used simultaneously and / or serially to process a volume of therapeutic suspension and / or a plurality of volumes of a different therapeutic suspensions (e.g., different types of therapeutic suspension and / or different volumes, or vials, of the same therapeutic suspension). Use of array 501 may increase the efficiency and / or throughput of processing therapeutic suspensions, which may be useful when, for example, processing a relatively large volume of therapeutic suspension as may be the case when manufacturing or processing volumes of therapeutic suspensions and / or quickly processing a smaller volume of therapeutic suspension, which may be desirable when working with therapeutic suspensions and / or therapeutic agents that require fast processing time due to, for example, temperature and / or viability considerations and / or constraints. Array 501 may also be used when processing different types of therapeutic suspensions at the same time as may desirable when, for example, a patient is to receive infusions of two different therapeutic suspensions at the same time or nearly the same time (e.g., one right after the other). In another example, a plurality ofmicrofluidic devices may be arranged in parallel as shown in, for example, FIG. 5B, which is a schematic diagram of a top perspective view of a parallel array of microfluidic devices, wherein a first microfluidic device 314A with a first inertial feature 313A is positioned on top of a second microfluidic device 314B with a second inertial feature 316B. A volume of therapeutic suspension may be added to array 502 via an inlet port 312. Use of a plurality of microfluidic devices may be arranged in parallel may be beneficial when, for example, processing a volume of therapeutic suspension using multiple microfluidic devices is desired and / or practical to, for example, further refine, wash, and / or purify therapeutic agents included in a volume of therapeutic suspension.[000101] In some embodiments, one or more of the microfluidic devices disclosed herein may be provided as part of a kit of components or devices used to contain volumes of therapeutic suspension and / or media or substances used to process (e.g., wash, concentrate, incubate, enable gas exchange, etc.) a volume of therapeutic suspension according to, for example, one or more methods disclosed herein. Components included in the kits may be standardized and / or customized according to, for example, equipment used to process the therapeutic suspension, requirements for processing the therapeutic suspension (e.g., type and / or volume of wash media or incubation media required), a volume of therapeutic suspension being processed, and / or clinician, hospital, and / or patient preference. FIG. 6A provides a diagram of one exemplary kit 600 that includes a microfluidic device like microfluidic device 201 , containers in the form of a first bag 630A, a second bag 630B, a third bag 630C, a fourth bag 630D, and a fifth bag 630E. Kit 600 also includes a syringe 610 that may be coupled to a swivel adapter 615 that allows for the spinning, or rotation, of a barrel of syringe 610 without twisting or otherwise altering a position or orientation of a tube coupled to syringe 610, a vial 620 for the collection of processed therapeutic suspension, an air filter 625 configured to allow only sterile air (e.g., no bacteria, viruses, or other contaminants) to pass into vial 620, a therapeutic agent collection receptacle (in this instance embodied as a bag), 640, and a plurality of tubes and connectors that facilitate liquid communication between the components of kit 600. In some embodiments, the therapeutic agents may be directed to therapeutic agent collection receptacle 640 so that they may be pulled into syringe 610 following separation by, for example, microfluidic device 201 .[000102] In some cases, the tubes may have a relatively small wall thickness and / or be relatively deformable so that, for example, they may fit within and be pinched closed by a pinch valve. In some embodiments, the tubing may have an inner diameter of one-sixteenth (1 / 16) of an inch with an outer diameter of one-eighth (1 / 8) of an inch. Additionally, or alternatively, the tubing may have an inner diameter of one-thirty-second (1 / 32) of an inch or an inner diameter of one-eighth (1 / 8) of an inch. The dimensions of the tubing used may be responsive to, for example, a volume of therapeutic suspension being processed, dead volume within the system, and / or tolerances for the therapeutic suspension to forces, shear stress, and / or compressive stress. Often times, kit 600 may be sterilized in advance of use and / or provision to a user (e.g., sterilized at a manufacturing and / or assembling facility) via, for example, placing the kit in a bag to be sterilized via, for example, an autoclave. Additionally, or alternatively, kit components may be assembled in a sterile environment (e.g., clean room or under a culture hood) and then sealed in a bag or container. At times, some components of kit 600 may be provided pre-filled with required materials such as wash and / or culturing media and sterilized at the assembly facility.[000103] FIG. 6B is a detailed view of a portion of kit 600 that is proximate to microfluidic device 201 that shows a plurality of tubes coupled to microfluidic device 201 via connectors 310 embodied as leur connectors, wherein inlet port 205 is coupled to a source of therapeutic suspension (e.g., syringe 610, bag 630, vial, etc.) via first connector 310A and is in liquid communication with a second tube 645. A volume of therapeutic suspension may be communicated from second tube 645 to inlet port 205 and may begin to travel around primary channel 220 until it reaches outlet port 215 and is communicated to second inertial element feature 203 via first tube 250 as shown. Outlet port 217 of second inertial element feature 203 may be coupled to a third tube 647 via, for example, fifth connector 310E as shown. Third tube 647 may be in fluid communication with, for example, a receptacle (not shown) for the volume of concentrated therapeutic suspension and / or a patient delivery device (e.g., a catheter, bag, vial, and / or syringe). Waste outlet port 210 may be in fluid communication with, for example, a receptacle (not shown) for a volume of waste extracted from the therapeutic suspension via a fourth tube 657 and fourth connector 310D.[000104] The microfluidic devices disclosed herein may be configured for repetitive use. For example, on some occasions, microfluidic device 100, 200, 401 , and / or 402 and / or portions thereof may be used multiple times to progressively filter, process, wash, and / or prepare therapeutic agents and / or a therapeutic suspension for infusion into a patient. For example, a volume of therapeutic suspension may be passed through microfluidic device 100 a pre-set number (e.g., 2-10) of times and / or multiple times until a quality assurance measurement indicates that the therapeutic agents are sufficiently concentrated and / or a sufficient amount of waste has been removed from the therapeutic suspension (i.e., the therapeutic agents have been sufficiently washed).[000105] Additionally, or alternatively, the microfluidic devices disclosed herein may be used to process a volume of therapeutic suspension on, for example, a continuous basis without reducing an overall volume of therapeutic media. In these embodiments, a therapeutic suspension may be continuously through the microfluidic device(s) in a loop so that the inertial element features(s) focus the therapeutic agents toward the inner wall of the respective inertial element features while waste is pulled off and enters waste channels and / or subchannels. As this occurs, fresh media may be added to the therapeutic suspension so that the therapeutic agents remain suspended while looping through the inertial element features(s). Over time, the newly added fresh media will replace the undesired (e.g., original media or cryo-preservative agent), thereby washing the therapeutic agents and suspending them in fresh media. In this embodiment, a volume of concentrated therapeutic suspension may not be generated and a patient-ready therapeutic suspension may be prepared / generated instead.[000106] In some embodiments, repetitive use of one or more inertial element features may be enabled by a design and / or configuration of features of a microfluidic device and / or a set of microfluidic devices. For example, a first and second inertial element features may be coupled in, for example, a figure 8 fashion so that as the therapeutic suspension travels through the first inertial element features, then the second inertial element features, then the first inertial element features, then the second inertial element features, etc. waste may be pulled off the therapeutic suspension thereby increasing a concentration of therapeutic agents within the therapeutic suspension and / or when fresh media is added as the therapeutic media moves through a loop of inertial element features, the waste maybe replaced with fresh media, thereby preparing a volume of patient-ready therapeutic suspension.[000107] Additionally, or alternatively, two or more of the microfluidic devices disclosed herein may be arranged so that an outlet of a first microfluidic device is in fluid communication with an inlet of a second microfluidic device. For example, a first microfluidic device may be arranged on top of a second microfluidic device so that an outlet port (e.g., outlet port 115, 215, 217, and / or 416) is in fluid communication (e.g., is coupled to) an inlet port (e.g., inlet port 105, 205, 207, and / or 410) and, in this way, first and second microfluidic devices may be serially used to process therapeutic suspensions to, for example, concentrate therapeutic agents within a therapeutic suspension, remove waste from a therapeutic suspension, wash therapeutic agents, and / or prepare a patient-ready therapeutic suspension.[000108] Additionally, or alternatively, one or more of the microfluidic devices disclosed herein may include one or more additional components (e.g., channels, ports, inertial element features, curves, etc.) configured direct therapeutic suspension and / or another fluid into, out of, and / or through the microfluidic device and / or components connected thereto. These microfluidic devices may be configured to minimize dead volume that traps therapeutic suspension and / or other substances within the microfluidic devices and / or components coupled thereto. Additionally, or alternatively, one or more of the microfluidic devices disclosed herein may be configured and / or arranged so that movement into, out of, and / or through the respective microfluidic device is assisted by gravity. The microfluidic devices disclosed herein may also include and / or be coupled to one or more macro-fluidic elements and / or features that may be configured to use macro, or Newtonian (e.g., centrifugal and / or angular momentum) forces and / or momentum to move fluids and / or therapeutic suspension into, out of, and / or through a device.[000109] FIG. 7 provides a block diagram of an exemplary hydrodynamic focusing device and / or trap 700 (sometimes referred to herein as hydrodynamic trap 700) that may be employed with (e.g., resident on) and / or communicatively coupled to a microfluidic device like the microfluidic devices disclosed herein. Hydrodynamic trap 700 may be used to focus, concentrate, and / or trap particles (e.g., therapeutic agents) within certain regions thereof so that they may be removed therefrom and / or generate a relatively highly concentrated therapeutic media (e.g., 15-40million therapeutic agents / ml, 10-30million therapeutic agents / ml, 0.9-1 ,2million therapeuticagents per microliter, 1-1 .15million therapeutic agents per microliter, or 0.75- 1 ,4m illion therapeutic agents per microliter[000110] In the example of FIG. 7, hydrodynamic trap 700 includes a sample inlet port 705, a plurality (in this case, four) of buffer inlet ports 710A, 710B, 710C, ad 710D, a plurality (in this case, two) waste outlet ports 715A and 715B, a valve 720 (in this case, a pneumatic valve but other valve types are contemplated including, but not limited to, pinch valves and flap valves) and a plurality of channels 730 connecting the inlet and outlet ports. As depicted in FIG. 7, a volume of therapeutic media may enter hydrodynamic trap 700 via inlet port 705 and travel toward a sample focusing region 750 via a first channel 730A. Therapeutic agents present within the volume of therapeutic media be trapped, or concentrated, in first sample focusing region 750 by buffering solution introduced to hydrodynamic trap 700 via a first inlet port 710A and a second inlet port 710B and communicated to first sample focusing region 750 via second and third channels 730B and 730C and a constricted region of first channel 730A. A volume of therapeutic media that passes through first sample focusing region 750 travels toward a second sample focusing region 750B via a fourth channel 730D, which is physically coupled to first and second waste outlet ports 715A and 715B via fifth and sixth channels 730E and 730F, respectively, at a trapping region 755 configured to concentrate and / or trap therapeutic agents with the assistance of buffer provided via third and fourth buffer inlet ports 710C and 710D and sixth, seventh, and eighth channels 730G, 730H, and 730I. Waste (e.g., therapeutic media with a low concentration of therapeutic agents) may be evacuated from hydrodynamic trap 700 via first and / or second waste ports 715A and / or 715B. A flow rate and / or volume of waste evacuated from hydrodynamic trap 700 may be adjusted and / or regulated via operation of valve 720. Concentrated therapeutic agents may be removed from hydrodynamic trap 700 via a port and / or coupling (not shown) in communication with trapping region 755.[000111] In some embodiments, hydrodynamic trap 700 may create and / or apply a combination of a plurality (e.g., two or more) fluid flows to compress a single sample stream of therapeutic media by narrowing its width and aligning therapeutic agents (e.g., particles and / or cells) within the therapeutic media. Hydrodynamic trap 700 may be used to, for example, concentrate therapeutic agents within media by, for example, adjusting flow rates through channel geometry and / or adjusting channel geometry. At times, hydrodynamic trap 700 may be configured to apply and / or directmicrofluidic inertial effects and / or secondary flows (e.g., Dean flow in curved channels) to enhance, improve, and / or economize the therapeutic agent concentration process by, for example, directing therapeutic agents to specific regions of hydrodynamic trap 700 for extraction and / or eventual infusion into patient tissue.[000112] FIG. 8 is a diagram of an exemplary microfluidic device 800 that utilizes deterministic lateral displacement (DLD) to process therapeutic media and / or generate concentrated therapeutic media. Microfluidic device 800 includes a substrate 805 that provides an inlet port 810, a separation channel 815, a waste channel, and an outlet 825 for concentrated therapeutic media. Microfluidic device 800 may be used in one or more of the systems and / or devices disclosed herein to, for example, process a therapeutic suspension by, for example, separating therapeutic agents from waste (e.g., cryogenic media, dead cells, etc.), concentrating therapeutic agents in media, washing therapeutic agents contained in a volume of therapeutic media, and / or introducing additional material (e.g., infusion media and / or cell culture media).[000113] FIG. 9 is a diagram of a microfluidic device 900 that includes a viscoelastic microfluidic concentrator that directs cells into a concentrated area, or region, of microfluidic device 900 via the therapeutic media’s viscoelastic properties. In some instances, the viscoelastic microfluidic concentrator may increase the viscosity of the therapeutic media exiting microfluidic device 900, which may enable greater concentration of therapeutic agents within the therapeutic media with high rates of therapeutic agent recovery.[000114] In some embodiments, a device like microfluidic device 900 may be used to concentrate therapeutic agents within a therapeutic suspension and / or achieve high cell concentration at the outlet of the microfluidic device by, for example, using a viscoelastic fluid and its interaction with the flow stream of therapeutic media to concentrate therapeutic agents (e.g., cells or radioactive particles) and / or generate a highly-concentrated therapeutic media. Microfluidic device 900 may be used in addition and / or in alternative to one or more of the microfluidic devices disclosed herein to concentrate therapeutic agents within media (i.e., generate highly-concentrated therapeutic media).[000115] FIG. 10 is a block diagram of components that may be included in a therapeutic suspension preparation and / or infusion system 1000 that may be used inconjunction with one or more of the microfluidic devices disclosed herein to process and / or prepare a volume of therapeutic suspension and / or generate a volume of patient-ready therapeutic suspension. System 1000 includes a temperature regulation device 1010, an optional fan 1012, a power supply 1015, a first motor 1020, a user interface device 1025, a transceiver 1050, one or more ports 1055, a processor / controller 1040, a memory 1042, a second motor and / or pump 1045, a thermometer 1050, one or more valves 1055, and a source of compressed gas 155; all of which may be enclosed in a housing 1005. Additionally, or alternatively, one or more components of system 1000 may be resident within a separate device (i.e., not resident within housing 1005) that is in communication (e.g., electrical, liquid, and / or gaseous communication) with housing 1005 and / or another component of system 1000. Housing 1005 may be configured to house the components of system 1000 and may be made from any suitable material (e.g., metal, plastic, etc.). In some embodiments, housing 1005 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 1000 while in use and / or may allow system to be portable and / or used while at a patient’s bedside and / or chair.[000116] Temperature regulation device 1010 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 1010 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 1010 include, but are not limited to, resistance coils, water baths, refrigeration components, and / or warming plates. Often times, temperature regulation device 1010 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, one or more instructions that may be received from, for example, processor / controller 1040 and / or user interface device. For 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 1010 may include and / or be communicatively coupled to thermometer 1050,which may be configured to measure a temperature of, for example, a volume of therapeutic suspension, temperature regulation device 1010, and / or system 1000. Thermometer 1050 and may be further configured to provide the temperature to, for example, user interface device 1025, transceiver 1050, a port 1055, and / or processor / controller 1040. Fan 1012 may be configured to circulate air and / or heat provided by temperature regulation device 1010 within housing 1005, system 1000, and / or components thereof to achieve and / or maintain a desired temperature within system 1000.[000117] Power supply 1015 may be configured to provide electrical power to one or more components of system 1000 and may be, for example, a battery and / or a plug or circuitry configured to couple to an electrical main. First motor 1020 and / or second motor 1045 may be, for example, a stepper motor and / or a pump. First motor 1020 and / or second motor 1045 may be configured to rotate and / or move (e.g., vibrate, rock, and / or agitate) one or more components of system 1000. When first motor 1020 and / or second motor and / or pump 1045 are embodied as a pump, they may be configured to push and / or pull therapeutic suspension or other substances (e.g., waste and / or fresh media) through one or more therapeutic suspension processing devices such as the microfluidic devices disclosed herein. [000118] User interface device 1025 may be any device, or combination of devices, that are configured to enable a user to monitor an operation of a component of system 1000 and / or provide input and / or instructions (e.g., on / off) to a component of system 1000. Exemplary user interface device(s) 1025 include, but are not limited to, dials, optical scanners, RFID scanners, buttons, keyboards, display devices, speakers, microphones, and touch screens. When embodied as a scanner, or input device, user interface device 1025 may operate to accept and / or obtain identification information for one or more components of the systems, devices, kits, and / or components used with (e.g., vials of therapeutic suspension) disclosed herein.Additionally, or alternatively, user interface device 1025 may be configured to accept user and / or patient information, protocols for the operation of the system and / or processing of a volume of therapeutic suspension, etc.[000119] Transceiver 1050 may be configured to transmit and / or receive communication via, for example, wireless or wired (via e.g., a port 1055) communication. Exemplary received communications include, but are not limited to, instructions for operation, processes to be executed such as the processesdescribed herein, and / or other parameters for operation (e.g., start / stop times, run time duration, a number of times therapeutic suspension should be passed through a microfluidic device, a preferred concentration of therapeutic agents within a patientready volume of therapeutic suspension , a 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 1055 may be configured as, for example, power, user interface, and / or communication ports and may be coupled to, for example, transceiver 1050, controller / processor 1040 and / or memory 1042. In some embodiments, one or more ports 1055 may be configured to cooperate to enable liquid and / or gaseous communication with one or components of a system disclosed herein.[000120] Thermometer 1050 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 1050 may be coupled to processor / controller and / or temperature regulation device 1010 and activation of temperature regulation device 1010 may be responsive to a temperature measurement from thermometer 1050 that is received by processor / controller 1040 (which provides an activation instruction to temperature regulation device 1010) and / or temperature regulation device 1010 directly via, for example, a thermocouple or switch.[000121] The one or more valves 1055 may be configured to open and close according to, for example, instructions received from processor / controller 1040 and / or may be manually operated to facilitate movement of therapeutic suspension and other liquids and / or gasses throughout system 1000. 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 1055 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 gases from the system.[000122] Processor / controller 1040 may be programmed and / or configured to control an operation of one or more components of system 1000 according to, for example, one or more methods disclosed herein. For example, processor / controller 1040 may be configured to set and / or control a rate of rotation of first motor 1020, a rate of rotation of second motor 1045, a temperature achieved and / or maintained by temperature regulation device 1010, and / or communications sent out and / or received by transceiver 1050. Instructions for operating the processor / controller and / or executing one or more methods disclosed herein may be stored in memory 1042 and / or received from user interface 1023 and / or transceiver 1050. Additionally, or alternatively, processor / controller 1040 may be configured to receive instructions pertaining to an operation of system 1000 via, for example, user interface device 1025, a port 1055, and / or transceiver 1050. Additionally, or alternatively, processor / controller 1040 may be configured to provide information to a user regarding an operation of system 1000 via, for example, user interface device 1025, a port 1055, and / or transceiver 1050. Processor / controller 1040 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 defaulting 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 1040 may enable a user to override one or more default settings of system 1000 via, for example, user interface device 1025 and / or a software program running on an external computing device that may be in communication with transceiver 1050, a port 1055, and / or user interface device 1025.[000123] In some embodiments, temperature regulation device 1010, fan 1012, processor / controller 1040 and thermometer 1050 may cooperate as a thermalequilibrium system so that processor / controller 1040 controls the operation of temperature regulation device 1010 and fan 1012 responsively to a temperature (received from thermometer 1050) 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.[000124] At times, processor / controller 1040 and transceiver 1050 may cooperate to communicate with a software application running on, for example, a computer, tablet computer, and / or smart phone. Transceiver 1050 may use a wired and / or wireless (e.g., BLUETOOTH) communication protocol to communicate with the software application.[000125] FIG. 11 provides a block diagram of an exemplary system 1100 that may include one or more components of system 1000 as well as a base unit 1401 coupled to a plurality of devices including a cell collection chamber 1172, a microfluidic device, or microfluidic filter, 1175, an optional filtration device, or strainer, 1176, a first reservoir of wash media 1162, a second reservoir of wash media 1164, a waste reservoir 1166, cell culture media reservoir 1168, and an infusion media reservoir 1170. In some embodiments, microfluidic device, or microfluidic filter 1179 may include and / or be similar to one or more of the microfluidic devices disclosed herein (e.g., microfluidic devices 100, 200, 401 , and / or 402) and / or an array of microfluidic devices. First and / or second reservoir(s) of wash media 1162 and / or 1164 may store a volume of wash media that may be used to, for example, wash therapeutic agents and / or process a therapeutic suspension as, for example, described herein. Waste reservoir 1186 may be configured to be in liquid communication with one or more waste channels and / or waste subchannels as, for example, described herein. Reservoir of cell culture media 1168 may hold a volume of media used to culture biological therapeutic agents that may be in communication with one or more components of system 1100. Infusion media reservoir 1170 may be configured to hold a volume of infusion (or patient-ready) media to be added to concentrated therapeutic agents and / or used to prepare a volume of patient-ready therapeutic suspension as, for example, disclosed herein. The lines shown in FIG. 11 may be tubes, catheters, or the like and may facilitate movement of a volume of therapeutic suspension and / or other materials through system 1100 as, for example, described herein.[000126] System 1100 may be used in many different ways and / or different components of system 1100 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 a barrel 1110 (via, for example, pushing a plunger 1104 into barrel 1110) of an exemplary infusion and / or processing device 1102 and flow to microfluidic filter 1179 to be separated into waste, which is communicated to waste reservoir 1166, and a volume of concentrated therapeutic suspension, which may flow to cell chamber 1172. When barrel 1110 is empty and washing of the therapeutic agents is desired, third valve 1135C and / or second valve 1135B may be opened to allow wash media from first and / or second wash media reservoirs 1162 and / or 1164 to flow through cell chamber 1172 and into barrel 1110, which may act to resuspend the therapeutic agents held in cell chamber 1172 in the wash media. In some embodiments, wash media held by first and / or second wash media reservoirs 1162 and / or 1164 may be of a particular temperature (e.g., 5-37degrees Celsius) and may be used to defrost and / or thaw a frozen volume of original therapeutic suspension. Additionally, or alternatively, a volume of therapeutic suspension may be agitated (e.g., pulled out of and / or pumped into barrel 1110) during the thawing process to, for example, provide even temperature distribution (e.g., reduce hot spots) throughout the volume of therapeutic suspension.[000127] When infusion of the volume of concentrated therapeutic suspension is desired without washing or other processing, fourth valve 1135D may be opened so that the volume of concentrated therapeutic suspension flow from cell chamber 1172 to strainer 1176 and final output 1178 and / or directly to final output 1178 (i.e., without traveling through strainer 1176). Additionally, or alternatively, the volume of the concentrated therapeutic suspension may flow from microfluidic filter 1179 to strainer 1176 and final output 1178 and / or directly to final output 1178 (i.e., without traveling through strainer 1176) when fourth valve 1135D is opened.[000128] Optionally, system 1100 may include a gas exchange module 1180 configured to enable gas exchange (e.g., respiration) between therapeutic agents included in a volume of therapeutic suspension and module 1180. In some embodiments, gas exchange module 1180 may be embodied as a container of carbon dioxide that may be pulled into barrel 1110. Additionally, or alternatively, gasexchange module 1180 may include a container of carbon dioxide into which the therapeutic suspension is pumped and retained for a time period sufficient to allow for gas exchange. Then the therapeutic suspension may be extracted from the container and put back into barrel 1110 and / or transferred to another component of system 1100. Additionally, or alternatively, gas exchange module 1180 may include a sterile filter open to ambient air that the therapeutic suspension flows through. [000129] 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 1110, one or more hydrogel precursors may be added to barrel 1110 and mixed together via, for example, agitation and / or rotation of barrel 1110 with, for example, first and / or second motor 1020 and / or 1045.[000130] FIG. 12 is a schematic diagram of a top view of an exemplary base unit 1200 that may be used to, for example, process a therapeutic suspension using, for example, one or more of the microfluidic devices disclosed herein and / or infuse a therapeutic suspension into a patient. Base unit 1200 includes a housing 1205 configured to house a port 1247 (e.g., communication port, power port, electrical coupling, etc.) and one or more components described herein, such as the components of system 1000 (e.g., temperature regulation device 1010, optional fan 1012, power supply 1015, first motor 1020, user interface device 1025, transceiver 1030, one or more ports 1035, processor / controller 1040, memory 1042, second motor 1045, thermometer 1050, and source of compressed gas 1037). Base unit 1200 further includes a plurality of valves 1235 that may be similar to valves 1135. In the embodiment shown in FIG. 12, includes a first valve 1235A, a second valve 1235B, a third valve 1235C, a fourth valve 1235D, a fifth valve 1235E, and a sixth valve 1235G that may be, for example, omni-directional, bi-directional, pneumatic, pinch, and / or pressure-sensitive valves. Valves 1235 may be configured to, for example, couple to one or more components, containers, and / or sources of therapeutic media, resuspension media, and / or wash media as, for example, disclosed herein.[000131] Base unit 1200 also includes a device mount 1210 configured to hold and / or allow a device and / or therapeutic suspension container, such as an infusion and / or processing device 1102 therein. In some embodiments, device mount 1210may be configured to accept and / or cooperate with infusion and / or processing device 1102 of different sizes and / or capacity. For example, in some embodiments, device mount 1210 may be adjustable. Additionally, or alternatively, base unit 1210 may be configured to cooperate with device mounts 1210 of a plurality of sizes. In the embodiment of FIG. 12, infusion device mount 1210 includes a base 1212 on which a portion of infusion and / or processing device 602 (e.g., barrel 1110 as shown) may rest. Barrel 1110 may be held in place by a first and second retaining device 1214, which may be embodied as, for example, a piece of curved metal or plastic, an elastic band, and / or a strap. Base 1212 may further include and / or be proximate to a barrel agitation device 1216 that may be embodied as a device configured to engage with barrel 1110 via, for example, friction and / or a gear to rotate barrel 1110 around an axis within retaining device 1214 via, for example, cooperation with, for example, second motor 1220 and / or 1245. In some cases, barrel agitation device 1216 may be elastic and / or deformable (e.g., made from rubber or plastic) so that it may be placed over barrel 1110 or barrel 1110 may otherwise be coupled thereto. Rotation of barrel 1110 may serve to, for example, keep therapeutic agents in suspension, prevent adhesion of therapeutic agents to an internal surface of barrel 1110, and / or create a density gradient within a volume of therapeutic suspension held by barrel 1110. Base unit 1200 also includes a headplate 1220 that may be configured and / or function to engage with or otherwise press against a plunger 1222 and articulate along a track 1218 back (e.g., away from coupling 1244) and forth (e.g., toward coupling 1244) via, for example, motion generated via first motor 1220 so that, for example, plunger 1222 may be articulated within barrel 1110 to, for example, push a volume of therapeutic suspension out infusion and / or processing device 602 and / or create a vacuum within barrel 1110, 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 1110 or another component of base unit 1200 and / or a tube or device coupled thereto.[000132] As shown in FIG. 12, an optional thermal device 1240 may be added to and / or attached to base unit 1200. Thermal device 1240 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 1240 includes a base thermal plate 1241 and a top thermal plate 1242. When needed (e.g., when a frozen volume of volume of therapeutic suspension needs to be defrosted), thermal device 1240may be attached to base unit 1200 via one or more attachment mechanisms 1243, which may be embodied as pins or posts sized, positioned, and configured to correspond to openings in top and / or bottom thermal plate 1241 and / or 1242. In some embodiments, thermal device 1240 may be in communication with fan 1212, temperature regulation device 1010, and / or thermometer 1050 via, for example, a communicative, electrical, and / or thermal coupling.[000133] Base unit 1200 also includes an optional filter 1256 and a filter housing 1254 configured to hold filter 1256 while enabling coupling of filter 1256 to one or more components as, for example, described herein. Filter 1256 may be, for example, a housing for one or more layers of filtration material, a multi-component filter like a multi-component (e.g., multiple layers of a material and / or different materials, sieves, etc.) filters and / or a microfluidic device like the microfluidic devices disclosed herein.[000134] Base unit 1200 further includes an optional container holder 1250 configured to hold a container 1272 (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, base unit 1200 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. Additionally, or alternatively, base unit 1200 may be coupled to one or more containers of wash media, fresh resuspension media, and / or waste media.[000135] At times, an operation of base unit 1200, thermal device 1240, one or more valves 1235, headplate 1220, first motor 1220, and / or second motor 1245 and / or any device included in and / or coupled to base unit 1200 may be controlled and / or operated by processor / controller 1240 according to, for example, one or more inputs and / or instructions received from, for example, memory 1242, transceiver 1230, ports 1235, and / or user interface device 1225.[000136] In some embodiments, the filters described herein (e.g., microfluidic filter 1179, multi-component filters, and / or filter 1256) may be track etched membranes that comprise a membrane with holes track etched therein. The holes may be configured to allow therapeutic media (e.g., fluid) to pass through but not the therapeutic agents. The filter(s) may be of any appropriate geometry including, but not limited to, flat sheets, cylinders, and / or tubes. At times, the filters may be pairedwith a pumping mechanism configured to, for example, push therapeutic agents off the membrane without adding a dilutant by, for example, pumping a gas (e.g., air, sterilized air, medical gas, etc.) over the membrane so that capillary force of / at the air-membrane interface captures most therapeutic agents.[000137] The holes may be sized and / or configured to allow waste to pass through but may be too small for therapeutic agents to pass through so that the therapeutic agents remain on a surface of the filter. The therapeutic agents may be removed from a surface of the filter by, for example, flowing media over the filter and / or pumping air or another gas over the top of the filter to dislodge the therapeutic agents without adding additional dilutant.[000138] FIGs. 13A-13C are drawings of a top view of a first, second, and third exemplary scaffolds 1401 , 1102, and 1103, respectively and FIG. 13D is a side view of first, second, or third scaffolds 1401 , 1102, and 1103. First, second, and third scaffolds 1401, 1102, and 1103 that may be configured to sit over and / or above components (e.g., valves 1135 or 1235, infusion and / or processing device 1102, base mount 1210, etc.) via legs, or extensions 1340 to assist with organization of tubes and other components coupled to one or more pieces or components of a system (e.g., system 1100 or 1200) described herein by, for example, preventing tangling of tubes and / or the catching of tubes in an articulating component of the one or systems or devices disclosed herein. For example, first, second, and / or third scaffolds 1401, 1102, and 1103 may be configured to allow for the placement of one or more tubes of kit 600 thereon so that, for example, fluid moving through the tube may be more easily observed, tube pathways from a bag and / or container to a valve and / or container may be easily seen or deduced, and / or the tangling, twisting, breaking, and / or bunching the tubes may be prevented.[000139] First scaffold 1301 includes a plurality of clips, or clamps, 1320 positioned on two opposing sides of a first platform 1310A which is flat and, during use, a first side of a tube may be positioned within a first clip 1320 on a first side of first platform 1310A and extended over to a second clip 1320 positioned on the opposite side of first platform 1310A so that it is secured in place and then fed into a valve like valve 1135 or 1235. Second scaffold 1002 includes a plurality of grooves 1330 extending across two opposing sides of a second platform 1310B and, during use, a tube may be arranged to lay in a groove 1330 so that it may extend from a first side of second platform 1310B to a second side of second platform 1310B sothat it is secured in place and then fed into a valve like valve 1135 or 1235. Third scaffold 1003 includes a third platform 1310C that includes both the clips 1320 of first platform 1310A and the grooves of second platform 131 OB. First, second, and / or third platforms 1310A, 1310B, and / or 1310C may be flat, curved, pitched, and / or angled.[000140] In some embodiments, an assembly of a set of components for use with one of the systems described herein (e.g., kit 600) and a housing for the components like a tray and / or a scaffold like scaffold 1301 , 1002, and / or 1003 may be pre-assembled and sterilized for use so that a user may open a sterile bag including the assembly, extract the assembly, and arrange the assembly over one or more of the systems disclosed herein so that the tubes, vials, bags, etc. may be placed in their appropriate locations (e.g., valves, holders, mounts (e.g., device mount 1210) as shown in, for example, FIGs. 14, 12, and 13. In some embodiments, the assembly may be embodied as a thin tray or card with components of a kit attached thereto. The assembly may be placed over the system so that kit components (e.g., the tubing and bags) may be easily loaded into their respective valves / holders without tangling, obstructing, and / or kinking the tubes. Additionally, or alternatively, the assembly may be positioned on the system and the user may activate (e.g., pushes the assembly down or pulls a lever) engagement with the tubes and components of the kit so that the connections between the system and kit components are forced into place.[000141] FIG. 14 is a diagram of an assembly 1400 of the base unit 1200 and scaffold 1310A, 1310B, or 1310C, wherein scaffold 1310A, 1310B, or 1310C is positioned over a portion of barrel 1110, plunger 1222, and headplate 1220 to, for example, prevent one or more tubes or other objects (e.g., shirt sleeves, fingers, etc.) from disrupting or becoming caught by movement of plunger 1222 and / or headplate 1220 into and / or out of barrel 1110. In some embodiments, base unit 1200 and / or assembly 1400 may be coupled to and / or set up with one or more containers and / or tubes of a kit (e.g., kit 600) and, on some occasions, the containers and / or tubes may be arranged, oriented, and / or positioned so that gravity assists with movement of fluid (e.g., therapeutic media, processed therapeutic media, and / or waste) through a tube and / or into, or out of, a container.[000142] FIG. 15 is a block diagram of an exemplary fluid communication path through system 1100 or 1200, wherein a volume of therapeutic suspension entersand / or is pushed (via, for example, movement of headplate 1220 against plunger 1222 along track 1218) from infusion and / or processing device 1102 or 1202 into a microfluidic device like microfluidic device 100, 200, 300, 401 , 402, and / or a microfluidic device array like microfluidic device arrays 501 and / or 502 while first and second valves 1135A and 1135B are open. As the therapeutic suspension moves through microfluidic device 100, 200, 300, 401 , 402, and / or microfluidic device array 501 and / or 502, waste is drawn off into waste reservoir 1162 or 1264 via open first valve 1135A or 1235A and processed therapeutic suspension is drawn into processed therapeutic suspension reservoir 1186. Next, processed therapeutic suspension may be pulled into infusion and / or processing device 1102. Optionally, third valve 1135C or 1235C may be open while the processed therapeutic suspension is pulled into infusion and / or processing device 1102 to allow wash media to flow into infusion and / or processing device 1102 along with the processed therapeutic suspension. At times, the wash media may be warmed to assist with thawing a froze volume of therapeutic suspension and / or maintaining a preferred temperature for the therapeutic suspension. The therapeutic agents may be washed in this manner as many time as necessary or desired.[000143] Optionally, fifth valve 1135E or 1235E may be coupled to infusion media reservoir 1170 and fifth valve 1135E or 1235E may be open while the processed therapeutic suspension is pulled into infusion and / or processing device 1102 to allow infusion media to flow into infusion and / or processing device 1102 along with the processed therapeutic suspension once, for example, washing and / or processing of the therapeutic suspension is complete and / or prior to infusion of the therapeutic agents into a patient.[000144] Additionally, or alternatively, sixth valve 1135F or 1235F may be optionally coupled to infusion media reservoir 1170 and sixth valve 1135E 1235F may be open while the processed therapeutic suspension is pulled into infusion and / or processing device 1102 to allow cell culture media to flow into infusion and / or processing device 1102 along with the processed therapeutic suspension. This may be done when, for example, using infusion and / or processing device 1102 and / or a component of a system disclosed herein as a bioreactor and / or to culture or rehabilitate therapeutic agents embodied as cells and / or biological agents (e.g., viruses, DNA, etc.). Cell culture media may be removed from a therapeutic suspension over time to, for example, refresh cell culture media, replace cell culturemedia, wash therapeutic agents, and / or prepare a therapeutic suspension for infusion into a patient according to one or more methods disclosed herein.[000145] FIG. 16 is a schematic diagram of a perspective view of a system 1600 including base unit 1200 (a portion of which is illustrated as a box diagram) and an array 1610 including a plurality (in this case three) assemblies 300 (labeled as 300A, 300B, and 300C in FIG. 15) in fluid communication with waste reservoir 1166 (via valve 1235C), wash media reservoir 1162 (via valve 1235B), and processed therapeutic suspension reservoir 1120 (via valve 1235A). As shown in the embodiment of FIG. 16, infusion and / or processing device 1102 is in fluid communication with inlet ports 205 of each of microfluidic devices 300A, 300B, and 300C of array 1610 via a tube (shown with a heavy black line) in communication with fourth connector 310D; waste reservoir 1166 is in fluid communication with waste outlet ports 210 of each of microfluidic devices 300A, 300B, and 300C of array 1610 via a tube (shown with a dotted line) in communication with first connector 310A via valve 1235C; wash media reservoir 1162 is in fluid communication with outlet port 217 of each of microfluidic devices 300A, 300B, and 300C of array 1610 via a tube (shown with a thin black line) in communication with third connector 310C via valve 1235B; and processed therapeutic suspension media reservoir 1120 is in fluid communication with outlet port 217 of each of microfluidic devices 300A, 300B, and 300C of array 1610 via a tube (shown as a broken line) in communication with fifth connector 310E via valve 1235A. In addition, in some embodiments, second and third connectors 310B and 310C and their respective ports may be in fluid communication with one another via a tube extending therebetween as shown in FIG. 16.[000146] Flow of fluids (e.g., original therapeutic suspension, wash media, waste, etc.) through base unit 1200 and / or one or more microfluidic devices of array 1610 may be controlled by valves 1235 of base unit wherein an opening of second valve 1235B may introduce wash media into outlet ports 217 of each of the microfluidic devices of the assemblies of array 1610 and opening of first valve 1235A may allow for processed therapeutic suspension to enter processed therapeutic suspension reservoir 1120. Additionally, or alternatively, flow of fluids through base unit 1200 and / or one or more microfluidic devices of array 1610 may be controlled by movement of plunger 1222 within barrel 1210. The movement of plunger 1222and / or an operation (e.g., open or closed) of valve(s) 1235 may be manually controlled and / or controlled by, for example, processor / controller 1040.[000147] When system 1600 is in use, a volume of therapeutic suspension to be processed (e.g., original therapeutic suspension) may be pushed out of barrel 1110 via, for example, headplate 1220 pushing plunger 1222 into barrel 1110. The volume of therapeutic suspension to be processed may be pushed into one or more tubes (shown with heavy black line) toward one or more inlet ports 205. The volume of therapeutic suspension to be processed may then be processed by traveling through the inertial element features of the microfluidic devices of array 1610 whereby waste may be drawn off the volume of therapeutic suspension moving through the inertial element features and pulled, or pushed, into waste reservoir 1166 via first connectors 310A in communication with waste outlet ports 210. Then, processed therapeutic suspension may enter processed therapeutic suspension reservoir 1120 via fifth connector 310E and outlet port 217. Optionally, wash media from wash media reservoir 1162 and / or 1164 may be added to the microfluidic devices via outlet port 217 to wash the microfluidic devices to, for example, remove any therapeutic agents that may have adhered themselves to an inertial element features of a microfluidic device of array 1610.[000148] Although the systems shown herein include six valves, this need not always be the case. For example, a system may include any number (e.g., 2-40) valves and the size and / or configuration of the system may be adapted to accommodate the increased number of valves. Additionally, although system 1600 is shown to include base unit 1200, it may include any of the other base units described herein. Additionally, or alternatively, system 1600 may include a plurality of base units that are, for example, in fluid communication with an array like array 1610 in a series and / or parallel fashion.[000149] FIG 17A provides a top view and FIG. 17B provides a cross-section view of a nano filter 1700 configured to provide pores, or channels, that allow for the passage of materials (e.g., therapeutic media, buffering solution, washing solution, etc.) but are too small to allow for the passage of therapeutic agents. For example, FIG. 17C provides a top perspective view of nano filter 1700 that shows therapeutic agents 1710 resting on the upper surface of nano filter 1700 while the media has passed through the channels of nano filter 1700.[000150] Exemplary nano filters 1700 include the Whatman Nucleopore 3 micron pore, 47mm diameter membranes. In some embodiments, nano filter 1700 may be used before and / or after passing through one or more of the microfluidic devices described herein as, for example, a second stage of the filtering, concentrating, and / or processing of therapeutic media to concentrate therapeutic agents and / or removing the final few milliliters waste from therapeutic agents. Additionally, or alternatively, nano filter 1700 may be incorporated into one or more of the microfluidic devices disclosed herein to, for example, remove therapeutic agents from media and / or waste. At times, therapeutic agents may be removed from nano filter 1700 using air so that capillary force of the air-liquid interface captures the therapeutic agents for eventual transfer to a delivery device and / or storage in a storage device.[000151] FIG. 17D provides a diagram of an exemplary system 1701 for concentrating and / or processing therapeutic media that includes a nano filter like nano filter 1700. System includes a therapeutic media sample reservoir 1745 that holds a sample of therapeutic media ready for processing (e.g., washing, feeding, and / or refreshing) and / or concentration by system 1701, a pump (e.g., a syringe or container coupled to a source of negative and / or positive pressure) 1740, a processed therapeutic media container 1755, and a nano filter 1700, a cross-section view of which is provided by FIG. 17D. Nano filter 1700 includes a lid 1710, an inlet channel 1715, an array of pores 1720, a collection reservoir 1725, a waste outlet port 1735 (which may be coupled to a waste reservoir (not shown)), and an outlet port 1750.[000152] Therapeutic media sample reservoir 1745 is coupled to nano filter 1700 via a tube inserted into, or otherwise coupled to, inlet port 1730. Therapeutic media held in therapeutic media sample reservoir 1745 may enter nano filter 1700 via inlet port 1730. At times, the therapeutic media may be pulled from therapeutic media sample reservoir 1745 via negative pressure supplied by pump 1740. Upon exiting the therapeutic media sample reservoir 1745, the therapeutic media may enter inlet channel 1715 and pass over array of pores 1720. Pores 1720 may be sized and / or configured to allow waste, but not therapeutic agents, to pass therethrough so that the waste may collect in collection reservoir 1725. The waste may be evacuated from collection reservoir 1725 and pulled into pump 1740 and / or a container coupled thereto. The therapeutic media filtered by array of pores 1720 may be evacuatedfrom inlet channel 1715 and pulled into processed therapeutic media container 1755 via outlet 1750.[000153] In some instances, the negative pressure exerted by pump 1740 may act to pull therapeutic agents into the holes, or pores, of nano filter 1700.Additionally, or alternatively, adjustments to the amount of negative pressure applied to collection reservoir 1725 may act to adjust, regulate, and / or control a flow rate of therapeutic media through nano filter 1700.[000154] FIG. 18 is a diagram of an exemplary magnetic filter system 1800 that may be used with one or more of the microfluidic devices and / or systems disclosed herein to, for example, filter, or separate, therapeutic agents from waste and / or media. Magnetic system 1800 includes a magnetic filter 1801 and a magnet 1820. Magnetic filter 1801 comprises five legs, or sides 1810: a first side 1810A, an optional second side 1810B, a third side 1810C, a fourth side 1810D, and a fifth side 1810E. Each of first-fifth sides 1810E has a lumen therein. The lumens of first side 1810A and optional second side 1810B are in communication with the lumen of the third side 1810C and third side 1810C is in communication with fourth and fifth sides 1810D and 1810E as shown. First side 1810A includes an inlet port 1815, fourth side includes a waste outlet port 1820, and fifth side includes a processed therapeutic media outlet port 1825. During use, a combination of unprocessed therapeutic media and magnetic beads, or particles, that may be bound to therapeutic agents and / or suspended in a therapeutic suspension 1840 (also referred to herein as “suspension 1840”), may enter magnetic filter 1801 via inlet port 1815. As suspension 1840 flows past magnet 1820, the magnetized therapeutic agents therein are magnetically attracted to the magnet, thereby forming a processed (e.g., concentrated) therapeutic suspension 1850 and a waste stream 1845. Waste stream 1845 may continue through magnetic filter 1801 and exit waste outlet port 1820 and processed therapeutic suspension 1850 may continue through magnetic filter 1801 and exit processed therapeutic media outlet port 1825.[000155] FIG. 19 is a flowchart illustrating an exemplary process 11200 for processing a therapeutic suspension and / or infusing a therapeutic suspension into a patient using one or more systems, kits, devices, and / or methods disclosed herein. Process 11200 may be executed by a system like system 1000, 1100, and / or 1200 optionally using one or more components or kits disclosed herein like kit 600. Some steps of process 11200 may be executed via a graphic user interface (GUI) by whicha user may input information and / or instructions into a system like system 1100 and / or 1200 like GUI 2000 shown in FIG. 20. GUI2000 may be provided to the user via a user interface or display device like user interface device 1025 and / or user interface device 1225 which may be seen in FIG. 14. GUI 2000 may be configured to receive input via touch and / or activation via an interface device like a keyboard, trackpad, or mouse.[000156] Initially, in step 1905, information regarding, for example, a patient, a therapeutic suspension, and / or a protocol for processing and / or infusing a therapeutic suspension into a patient may be received via, for example, user input that may be received via a user interface like user interface device 1025, input received from a scanning device that may scan a code (e.g., optical code, alpha numeric code, etc.) associated with a therapeutic suspension and / or patient. Information pertaining to a type of therapeutic suspension received in step 1905 includes, but it’s not limited to, a type, volume, count of therapeutic agents (e.g., a cell count) present in the therapeutics suspension, viability information for the therapeutic suspension, and a status (e.g., frozen, defrosted, washed, etc.) for a therapeutic suspension.[000157] In some embodiments, information received at step 1905 may pertain to equipment used to process a therapeutic suspension and / or infuse the therapeutic suspension into a patient. Additionally, or alternatively, information received in step 1905 may include information about an environment (e.g., temperature, humidity, sterility conditions, etc.) and / or facility (e.g., hospital, operating room, clinic, residence, etc.) in which the therapeutic suspension is prepared, processed, and / or infused into the patient.[000158] Optionally, in step 1910, information regarding components of a system to process and / or infuse the therapeutic suspension into a patient may be received. For example, if a kit like kit 600 is being used with a system like system 1100 or 1200, identifiers for the kit and / or system may be received in step 1910. In some embodiments, step 1905 and / or 1910 may be executed by scanning one or more optical (e.g., bar or QR codes) associated with a system, kit, component, or volume of therapeutic suspension being used.[000159] Optionally, in step 1915, one or more databases, may be queried for additional information regarding, for example, the therapeutic suspension, the patient, a protocol for preparing processing, and / or infusing the therapeuticsuspension, medical records for the patient, specific instructions from a clinician such as a treating physician, and / or patient specific instructions may be received. [000160] In step 1920, one or more therapeutic suspension, processing, and / or infusion protocols may be accessed and / or generated using information received in steps 1905, 1910, and / or 1915. In some embodiments, step 1920 may be executed via, for example, using information received in steps, 1905, 1910, and / or 1915 to query memory 1042 and / or an external database for one or more sets of instructions regarding the processing and / or infusing of a therapeutic suspension.[000161] In step 1925, information regarding the therapeutic suspension processing and / or infusion protocols may be provided to a user along with optional request for further information or initiation instructions. And some embodiments, step 1925 may be executed via information and / or graphics provided via a GUI such as GUI 2000. As may be seen in FIG. 20, GUI 2000 may provide information in the form of a temperature of a syringe (in this case, 21 .8 degrees Celsius), a therapeutic suspension container (in this case, a bag) temperature of 22.0 degrees Celsius, a step number indicating what step in the preparation and / or infusion process the system is currently performing, a line that shows user entered commands, home button, reset button, temperature control buttons for the container of therapeutic suspension and syringe, a load file button that may enable the system to accept one or more files or set instructions regarding the processing and / or infusion of the therapeutic suspension. GUI 2000 also includes a start / stop button and toggle or joy buttons / icons by which a user can start and / or stop a therapeutic suspension preparation, processing, and / or infusion process.[000162] Optionally, instead 1930, user input may be received via, for example, a GUI like GUI 2000. The user input may be to stop or start a therapeutic suspension preparation, processing, and / or infusion process and / or adjust a parameter (e.g., temperature, washing steps, etc.) thereof. In some cases, the therapeutic suspension processing and / or infusion protocols of step 1920 may be updated and adjusted responsibly to the user input (step 1935).[000163] In step 1940, an instruction to begin execution of the therapeutic suspension processing, and / or infusion protocols may be received via, for example, receiving user input in the form of user pressing the start / stop icon of GUI 2000. Then, execution of the therapeutic suspension processing and / or infusion protocol may commence and be performed until complete (step 1945) as may be indicatedby, for example, the therapeutic suspension processing and / or infusion protocols of steps, 1920 and 1935.[000164] FIG. 21 is a block diagram of an exemplary self-sterilizing syringe 2100 that includes a syringe body, or barrel, 2105, that includes a first portion 2110 in which a volume of therapeutic media may reside and a second portion 2115 in which a volume of sterilant 2150 may reside. First portion 2110 and second portion 2115 may be separated from one another by a main gasket 2140, which may be positioned at an end of a plunger rod 2135 that may pushed into and / or pulled out of syringe body 2105 via pushing or pulling, respectively, on a plunger handle 2145. Self-sterilizing syringe 2100 further includes a plunger rod gasket 2135 configured to seal an end of barrel 2105 as plunger rod 2135 articulates into and out of second portion 2115 of syringe barrel. Self-sterilizing syringe includes a reservoir of sterilant 2120 and when plunger rod 2135 articulates toward first portion 2110 sterilant may be drawn from reservoir 2120 into second portion 2115 so that an interior surface of barrel 2105 and / or first portion 2105 may be coated with the sterilant and, therefore, sterilized. When plunger rod 2135 is pulled out of syringe barrel 2105 and first section 2110 main gasket 2140 may act to pull the sterilant into second portion 2115 and reservoir 2120. In this way, self-sterilizing syringe 2100 may be used more than once to, for example, accept and / or dispense therapeutic media as, for example, described and shown herein.

Claims

CLAIMSWe claim:1 . A microfluidic device comprising: a substrate; a first inertial element feature positioned on and / or in the substrate, the first inertial feature comprising; a primary channel with a first end and a second end; a first inlet port positioned proximate to, and in fluid communication with, the first end of the primary channel; a first outlet port positioned proximate to, and in fluid communication with, the second end of the primary channel; a first waste line configured and positioned to allow for extraction of waste from a suspension passing through the first inertial element features; and a first portion of a waste channel; and a second inertial element feature positioned on and / or in the substrate, the second inertial feature comprising; a secondary channel with a first end and a second end; a second inlet port positioned proximate to, and in fluid communication with, the first end of the secondary channel; a second outlet port positioned proximate to, and in fluid communication with, the second end of the secondary channel; a second waste line configured and positioned to allow for extraction of waste from a suspension passing through the second inertial element features; and a second portion of the waste channel.

2. The microfluidic device of claim 1 , further comprising: a plurality of waste subchannels extending from the primary channel to the first portion of the waste channel.

3. The microfluidic device of claim 1 or 2, wherein at least one of the primary channel and the secondary channel are spiral shaped.

4. The microfluidic device of any of claims 1-3, wherein at least one of the primary channel and the secondary channel are configured to create an inertial gradient in a volume of therapeutic suspension flowing therethrough that acts to concentrate, or pull, the therapeutic agents toward a center and / or interior edge of the at least one primary channel and secondary channel spiral and push waste media and debris toward an outer edge of the at least one primary channel and secondary channel as the volume of therapeutic suspension moves along the at least one primary channel and secondary channel.

5. The microfluidic device of any of claims 1-4, further comprising: a plurality of waste subchannels extending from the primary channel to the first portion of the waste channel, wherein at least one of the primary channel and the secondary channel are configured to create an inertial gradient in a volume of therapeutic suspension flowing therethrough that acts to concentrate, or pull, the therapeutic agents toward a center and / or interior edge of the at least one primary channel and secondary channel spiral and push waste toward an outer edge of the at least one primary channel and secondary channel as the volume of therapeutic suspension moves along the at least one primary channel and secondary channel, wherein the waste is drawn into a waste subchannel of the plurality of waste subchannels for evacuation from the microfluidic device via the waste channel.

6. The microfluidic device of any of claims 1-5, further comprising: a tube connecting the first outlet port to the second inlet port, the tube enabling fluid communication between the first outlet port to the second inlet port.

7. The microfluidic device of any of claims 1-6, further comprising: a cover, the cover configured to cover at least a portion of the substrate.

8. The microfluidic device of claim 7, wherein the cover has one or more openings configured to allow communication with at least one of the first inlet port, the first outlet port, the second inlet port, the second outlet port, and a waste channel outlet port in communication with the waste channel.

9. The microfluidic device of any of claims 1-8, further comprising:a first coupling in communication with the first inlet port; a second coupling in communication with the first outlet port; a third coupling in communication with the second inlet port; a fourth coupling in communication with the second outlet port; and a fifth coupling in communication with a waste channel outlet port.

10. The microfluidic device of claim 8, further comprising: a tube connecting the second coupling and the third coupling, the tube enabling fluid communication between the first outlet port to the second inlet port.11 .The microfluidic device of claim 8 or 9, wherein the first coupling is configured to communicate a volume of a therapeutic suspension to the first inlet port.

12. The microfluidic device of claim 8, 9, or 10, wherein the fourth coupling is configured to extract a volume of processed therapeutic suspension from the second outlet port.

13. The microfluidic device of any of claims 8-11 , wherein the fifth coupling is configured to extract a volume of waste from the waste channel outlet port.

14. The microfluidic device of any of claims 8-11 , further comprising a cover has one or more openings configured to allow communication with at least one of the first inlet port, the first outlet port, the second inlet port, the second outlet port, and a waste channel outlet port in communication with the waste channel, wherein the first, second, third, fourth, and fifth couplings are physically coupled to, and extend from, the cover.

15. The microfluidic device of any of the above claims, further comprising: a third inertial element feature positioned on and / or in the substrate, the third inertial feature comprising; a third channel with a first end and a second end; a third inlet port positioned proximate to, and in fluid communication with, the first end of the third channel;a third outlet port positioned proximate to, and in fluid communication with, the second end of the third channel; a third waste line configured and positioned to allow for extraction of waste from a suspension passing through the third inertial element features; and a third portion of the waste channel.

16. The microfluidic device of claim 17, further comprising: a tube connecting the second outlet port to the third inlet port, the tube enabling fluid communication between the second outlet port to the third inlet port.

17. A system configured to process a therapeutic suspension, the system comprising: a plurality of microfluidic devices of any of claims 1-16 connected in series with one another so that an outlet port of a first microfluidic device of the plurality of microfluidic devices is in communication with an inlet port of a second microfluidic device of the plurality of microfluidic devices.

18. A system configured to process a therapeutic suspension, the system comprising: a plurality of microfluidic devices of any of claims 1-16 connected in parallel to one another so that each microfluidic device of the plurality of microfluidic devices an outlet port of a first microfluidic device of the plurality of microfluidic devices is in communication with an inlet port of a second microfluidic device of the plurality of microfluidic devices.

19. A system configured to process a therapeutic suspension, the system comprising: the microfluidic device of any of claims 1 -16; a processing device including a first, second, third, and fourth valve; a first container configured to hold a volume of the therapeutic suspension, the first container being in communication with the processing device via a first tube coupled first container and the processing device, the first tube being in communication with the first valve;a second container configured to hold a volume of wash media, the second container being in communication with the processing device via a second tube coupled second container and the processing device, the second tube being in communication with the second valve; a third container configured to hold a volume of waste, the third container being in communication with the processing device via a third tube coupled third container and the processing device, the third tube being in communication with the third valve; and a fourth container configured to hold a volume of processed therapeutic suspension, the fourth container being in communication with the processing device via a fourth tube coupled fourth container and the processing device, the fourth tube being in communication with the fourth valve, wherein communication between the first, second, third, and fourth containers is controlled by the processing device.

20. The system of claim 19, wherein communication between the first, second, third, and fourth containers is controlled by the processing device when it opens and / or closes one or more of the first, second, third, and fourth valves.21 .The system of claim 19 or 20, wherein the first container is a syringe that includes a barrel that holds the volume of the therapeutic suspension and a plunger in communication with the barrel, wherein the volume of the therapeutic suspension enters the first tube when the plunger is pushed into the barrel.

22. The system of claim 21 , wherein the syringe is a self-sterilizing syringe.

23. The system of claim 21 or 22, wherein the processing device is configured to open the first valve so that a portion of the volume of therapeutic suspension may be communicated to the first inlet port of the microfluidic device.

24. The system of any of claims 21-23, wherein the processing device further comprises: a fifth valve; and a cell culture media container configured to hold a volume of cell culture media infusion media, the cell culture media container being in communication with theprocessing device via a fifth tube coupled cell culture media container and the processing device, the fifth tube being in communication with the fifth valve.

25. The system of any of claims 21-24, wherein the processing device further comprises: a sixth valve; and an infusion media container configured to hold a volume of infusion media infusion media, the infusion media container being in communication with the processing device via a sixth tube coupled infusion media container and the processing device, the sixth tube being in communication with the sixth valve.

26. The system of any of claims 21-25, further comprising: a filter configured to capture therapeutic agents suspended in the volume of therapeutic suspension and allow waste to flow therethrough.

27. The system of claim 26, wherein the processing device is configured to open the first valve so that a portion of the volume of therapeutic suspension may be communicated to the filter and waste media that flows through the filter may be communicated to the third container.

28. The system of claim 26, wherein the processing device is configured to open the first valve so that a portion of the volume of therapeutic suspension may be communicated to the filter and therapeutic agents captured by the filter may be communicated to the fourth container.

29. The system of any of claims 26-28, wherein the filter is a nano filter, a magnetic filter system, a hydrodynamic focusing device, hydrodynamic focusing trap, a deterministic lateral displacement device, and a viscoelastic microfluidic concentrator.

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