WO2022040383A1 - Systems, methods, and automation kits for magnetic isolation and/or enrichment of target analytes - Google Patents

Abstract

An in-field modification kit configured to convert a manually operated magnet assembly to an at least partially automated system can include (i) a door assembly configured to selectively attach to a magnet assembly, (ii) an elevation system configured to secure to the magnet assembly and to engage at least a portion of the door assembly for selectively adjusting a distance between the door assembly and the magnet assembly, (iii) a circular reciprocation system configured to engage a fulcrum of the magnet assembly and to selectively rotate the magnet assembly, and (iv) a valve manifold operably connected to the elevation system and the circular reciprocation system for executing automated protocols of magnetic isolation and/or enrichment of target analytes.

Description

SYSTEMS, METHODS, AND AUTOMATION KITS FOR MAGNETIC ISOLATION AND/OR ENRICHMENT OF TARGET ANALYTES

BACKGROUND

Technical Field

[0001] This disclosure relates generally to bioprocessing systems. More specifically, the present disclosure relates to systems, methods, and automation kits for magnetic separation of analytes.

Related Technology

[0002] Magnetic beads are routinely used in commercial and academic laboratories to isolate and/or enrich a target analyte. The term “analyte” or “target analyte,” as used herein, encompasses any chemical, protein, nucleic acid, or molecular motif that is targeted or identified through or during an assay. A target analyte can be a free compound within a solution or mixture and/or it may be a component part of a larger structure. For example, an analyte can include a surface-bound cellular receptor that when targeted, effectively isolates an entire cell associated with the targeted receptor. In this way, the term “analyte” or “target analyte,” particularly as used herein, can include a specified cell, targeted cell type, viral particles, and/or virions.

[0003] Advances in magnetic bead technologies have made it possible to customize the analyte- specificity of the magnetic beads. Among other things, this has enabled the positive isolation of a desired cell type from whole blood or other source of mixed cell types as well as the ability to deplete unwanted cell populations from a sample prior to downstream use or application. For example, by mixing magnetic beads that have been coated with an antibody targeting a known cluster-of-differentiation (CD) molecule into a non-homogenous sample, it is possible to selectively bind the magnetic beads to the surface- associated CD molecules of a desired cell type. Applying a magnet to the sample causes the magnetic beads to be attracted and bound within a localized area within the sample, carrying with them the associated CD-specific cells. The unbound cells and sample components in solution can then be removed and thereby effectively isolate or enrich the magnetic -bead-bound cells from the original sample.

[0004] For example, T-cells can be positively selected from the PBMC fraction of a whole blood sample using CD3/CD28 magnetic beads. The beads can be added to whole blood where they associate with CD3/CD28 positive cells (z.e., T-cells). Passing the magnetic-bead-containing whole blood through a magnetic field pulls the magnetic beads from solution along with any CD3/CD28 positive T-cells bound thereto. These isolated T-cells can be purified away from the magnetic beads and subsequently stimulated or expanded for experimental or clinical applications. [0005] Unfortunately, many of the systems used for magnetic bead capture rely on manual protocols that are prone to user error. This, in turn, greatly hinders the efficacy, reliability, and repeatability of experimental and clinical results, which could slow or prevent the development of therapeutics and/or waste valuable, limited sample.

[0006] Accordingly, there are a number of disadvantages with current systems and methods for magnetic separation of analytes that can be addressed.

BRIEF SUMMARY

[0007] Implementations of the present disclosure solve one or more of the foregoing or other problems in the art of magnetic separation of analytes. In particular, one or more embodiments can include an in-field modification kit configured to convert a manually operated magnet assembly to an at least partially automated system. An exemplary kit can include, among other things, (i) a door assembly configured to selectively attach to a magnet assembly, (ii) an elevation system configured to secure to the magnet assembly and to engage at least a portion of the door assembly for selectively adjusting a distance between the door assembly and the magnet assembly, (iii) a circular reciprocation system configured to engage a fulcrum of the magnet assembly and to selectively rotate the magnet assembly, and (iv) a controller and/or valve manifold operably connected to the elevation system and the circular reciprocation system for executing automated protocols of magnetic isolation and/or enrichment of target analytes or the beads themselves (e.g., following cell expansion).

[0008] In some embodiments, the door assembly of the in-field modification kit includes a door body, a front door pivot that is fastened to a proximal portion of the door body, and a rear door pivot that is fastened to a distal portion of the door body. The front door pivot can include at least one bracket fastened to the proximal portion of the door body; this bracket can retain a corresponding dowel that allows the door body to be secured in a closed position with respect to the magnet assembly. The front door pivot can also include a tube routing feature. The rear door pivot can include a pair of brackets fastened to the distal portion of the door body, and when fastened to the door body, each bracket is separated from the other by a rod that spans a space therebetween. In some embodiments, the door assembly includes a plurality of fasteners for securing a sample bag to an underside of the door body.

[0009] In some embodiments, the elevation system of the in-field modification kit includes a front elevation system configured to be secured to a proximal face of the magnet assembly and to engage the proximal portion of the door body. Such a front elevation system can include (i) a linear actuator having a stationary body and a movement arm, (ii) an actuator mount for securing the stationary body to the proximal face of the magnet assembly, and (iii) an actuator block secured to a proximal end of the movement arm. The front elevation system can additionally include a doorknob that is secured to, and rotatable about, the actuator block, for securing the front elevation system to the door body when the door body is in a closed position. In some embodiments, the doorknob includes a slot formed therein that is oriented, sized, and shaped to receive the corresponding dowel of the front door pivot such that when the corresponding dowel is passed through the slot and into an axially-aligned channel formed in the actuator block, misalignment of the slot with the dowel secures the door body in a closed position with respect to the magnet assembly.

[0010] In some embodiments, the front elevation system includes a tube routing block selectively securable to the stationary body of the linear actuator. The tube routing block can include a pair of tube routing features formed therein and positioned on opposing sides of the tube routing block in a direction substantially parallel to a movement direction of the movement arm. The tube routing block can, in one aspect, include an additional tube routing feature formed therein that is oriented in a direction transverse to the pair of tube routing features.

[0011] In some embodiments, the linear actuator of the front elevation system is a pneumatic cylinder or an electric linear actuator.

[0012] In some embodiments, the in-field modification kit includes a rear elevation system configured to be secured to a distal face of the magnet assembly and to engage a distal portion of the door body. Such a rear elevation system can include (i) a rear linear actuator comprising a rear stationary body and a rear movement arm, (ii) a rear actuator mount for securing the rear stationary body to the distal face of the magnet assembly, and (iii) a rear actuator block secured to a proximal end of the rear movement arm. In some embodiments, the rear elevation system includes a slot formed into the rear actuator block for securing the rear elevation system to the door body. Such a slot can be sized and shaped to receive the rod of the rear door pivot.

[0013] In some embodiments, the linear actuator of the rear elevation system is a pneumatic cylinder or an electric linear actuator.

[0014] The circular reciprocation system of the in-field modification kit, in some embodiments, can include a rotary actuator having a housing and a rotating element and an anchor assembly for securing the rotary actuator to the fulcrum of a corresponding magnet assembly and/or to a stand supporting the fulcrum such that a rotational force exerted by the rotary actuator is transferred to the fulcrum and/or magnet assembly. In some embodiments, the anchor assembly includes an anchor mount for securing the rotary actuator housing to the stand supporting the fulcrum. The anchor assembly can additionally include an actuator interface securable to the rotating element of the rotary actuator and a force plate configured to interact with the actuator interface and with the magnet assembly. For example, an engagement feature on a central post extending from the actuator interface can be sized and shaped to mate with a complementary engagement feature formed by the force plate of the anchor assembly, thereby enabling interaction — and force transfer — between the rotary actuator and the fulcrum and/or magnet assembly. In some embodiments, the force plate additionally includes a boss for assisting the force plate in transferring force from the rotary actuator to the magnet assembly (e.g., by pinning the force plate to the magnet assembly).

[0015] In some embodiments, the in-field modification kit includes a sensor, such as a bubble sensor, that can be selectively associated with the housing of the rotary actuator.

[0016] In some embodiments, the rotary actuator is a pneumatic rotary actuator or a stepper motor.

[0017] The present disclosure additionally includes methods for the magnetic isolation and/or enrichment of target analytes. An exemplary method includes processing a sample bag containing the target analyte and target- analyte specific magnetic beads on an analyte isolation and/or enrichment system retrofitted with an in-field modification kit as disclosed herein.

[0018] Automated systems for the magnetic isolation and/or enrichment of target analytes are also disclosed herein. For example, a system for the magnetic isolation and/or enrichment of target analytes can include (i) an analyte isolation and/or enrichment system retrofitted with an in-field modification kit, as disclosed herein and (ii) a computer system in electrical communication with the controller and/or valve manifold of the analyte isolation and/or enrichment system. The computer system can include, among other things, processor(s) and hardware storage device(s) having computer executable instructions stored thereon that, when executed by the processor(s), configure the computer system to initiate a predefined or user-defined protocol for isolating and/or enriching the target analyte. Such protocol(s) can include, in some embodiments, activating the elevation system to compress a sample bag associated with the door assembly against the magnet assembly such that the contents of the bag are within the operable magnetic field of the magnet assembly and simultaneously or serially activating the circular reciprocation system to rotate the magnet assembly and associated sample bag between elevated and lowered positions.

[0019] Accordingly, systems, methods, and in-field modification kits for the magnetic separation of target analytes are disclosed.

[0020] This summary is provided to introduce a selection of concepts in a simplified form that are further described below in the detailed description. This summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used as an indication of the scope of the claimed subject matter.

[0021] Additional features and advantages of the disclosure will be set forth in the description which follows, and in part will be obvious from the description, or may be learned by the practice of the disclosure. The features and advantages of the disclosure may be realized and obtained by means of the instruments and combinations particularly pointed out in the appended claims. These and other features of the present disclosure will become more fully apparent from the following description and appended claims or may be learned by the practice of the disclosure as set forth hereinafter.

BRIEF DESCRIPTION OF THE DRAWINGS

[0022] In order to describe the manner in which the above recited and other advantages and features of the disclosure can be obtained, a more particular description of the disclosure briefly described above will be rendered by reference to specific embodiments thereof, which are illustrated in the appended drawings. It is appreciated that these drawings depict only typical embodiments of the disclosure and are not therefore to be considered to be limiting of its scope. The disclosure will be described and explained with additional specificity and detail through the use of the accompanying drawings in which: [0023] FIG. 1A illustrates a front, top perspective view of a magnet assembly retrofitted with an in-field modification kit to enable automated protocols for magnetic bead capture of analytes within a sample, in accordance with one or more embodiments of the present disclosure;

[0024] FIG. IB illustrates a back top perspective view of the system illustrated in FIG. 1A, in accordance with one or more embodiments of the present disclosure;

[0025] FIG. 2A illustrates an isolated, top perspective view of the door assembly shown in FIGs. 1A and IB, in accordance with one or more embodiments of the present disclosure;

[0026] FIG. 2B illustrates an isolated plan view of the door assembly of the door assembly shown in FIGs. 1A and IB, in accordance with one or more embodiments of the present disclosure; [0027] FIG. 2C illustrates an isolated, bottom perspective view of the door assembly shown in FIGs. 1A and IB, in accordance with one or more embodiments of the present disclosure;

[0028] FIG. 3A illustrates a front perspective view of the door assembly of FIGs. 2A-2C shown in association with front and rear elevation systems, in accordance with one or more embodiments of the present disclosure;

[0029] FIG. 3B illustrates an isolated, front perspective view of the front elevation system shown in FIG. 3A, in accordance with one or more embodiments of the present disclosure;

[0030] FIG. 3C illustrates an isolated, rear perspective view of the front elevation system shown in FIG. 3A, in accordance with one or more embodiments of the present disclosure;

[0031] FIG. 4A illustrates a rear perspective view of the door assembly of FIGs. 2A-2C shown in association with front and rear elevation systems, in accordance with one or more embodiments of the present disclosure;

[0032] FIG. 4B illustrates an isolated, front perspective view of the rear elevation system shown in FIG. 4A, in accordance with one or more embodiments of the present disclosure;

[0033] FIG. 4C illustrates an isolated, rear perspective view of the rear elevation system shown in FIG. 4A, in accordance with one or more embodiments of the present disclosure;

[0034] FIG. 5 A illustrates a rear perspective view of the circular reciprocation system of FIGs. 2A-2C shown in association with the rotational axis or fulcrum of the magnet assembly, in accordance with one or more embodiments of the present disclosure;

[0035] FIG. 5B illustrates an isolated, rear perspective view of the circular reciprocation system shown in FIG. 5A, in accordance with one or more embodiments of the present disclosure; [0036] FIG. 6A depicts the flow pattern of fluid through a common, commercially available solution bag having a welded portion between the inlet and outlet of the solution bag;

[0037] FIG. 6B illustrates an exemplary flow pattern imposed upon a solution bag by a modified door panel, in accordance with one or more embodiments of the present disclosure;

[0038] FIG. 7 illustrates a schematic for connecting the valve manifold shown in FIGs. 1A and IB to a front elevation system, a rear elevation system, and a circular reciprocation system and to a computing system to enable and control automated protocols for magnetic bead capture of analytes, in accordance with one or more embodiments of the present disclosure.

DETAILED DESCRIPTION

[0039] Before describing various embodiments of the present disclosure in detail, it is to be understood that this disclosure is not limited to the parameters of the particularly exemplified systems, methods, apparatus, products, processes, and/or kits, which may, of course, vary. Thus, while certain embodiments of the present disclosure will be described in detail, with reference to specific configurations, parameters, components, elements, etc., the descriptions are illustrative and are not to be construed as limiting the scope of the claimed invention. In addition, the terminology used herein is for the purpose of describing the embodiments and is not necessarily intended to limit the scope of the claimed invention.

[0040] Furthermore, it is understood that for any given component or embodiment described herein, any of the possible candidates or alternatives listed for that component may generally be used individually or in combination with one another, unless implicitly or explicitly understood or stated otherwise. Additionally, it will be understood that any list of such candidates or alternatives is merely illustrative, not limiting, unless implicitly or explicitly understood or stated otherwise.

[0041] In addition, unless otherwise indicated, numbers expressing quantities, constituents, distances, or other measurements used in the specification and claims are to be understood as being modified by the term “about,” as that term is defined herein. Accordingly, unless indicated to the contrary, the numerical parameters set forth in the specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained by the subject matter presented herein. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the subject matter presented herein are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical values, however, inherently contain certain errors necessarily resulting from the standard deviation found in their respective testing measurements.

[0042] Any headings and subheadings used herein are for organizational purposes only and are not meant to be used to limit the scope of the description or the claims.

Overview Of Magnetic Bead Capture Systems

[0043] As briefly discussed above, magnetic beads are routinely used in commercial and academic laboratories for the isolation and/or enrichment of specific targets from solution. Various types of magnetic beads are commercially available and run the gamut of binding specificity and flexibility in application. For example, an antibody raised with specificity to target analyte can be conjugated to the surface of magnetic beads and used to directly capture its target analyte from solution. Alternatively, magnetic beads can be used to indirectly capture a target analyte. Instead of adding antibody-bound magnetic beads to the sample solution that are specific to a target analyte, the solution can be incubated with an analyte- specific primary antibody, allowing the antibody to target and specifically bind its corresponding analyte within the solution. Magnetic beads conjugated to the animal- specific Fc region of the primary antibody can then be added to the solution as, effectively, a secondary antibody for binding to the primary antibody. The analyte- antibody-antibody-magnetic bead complex can be easily pulled from solution by applying a magnetic field to bind the magnetic beads.

[0044] Magnetic bead technologies have advanced to the point where bespoke specificity of magnetic beads to a given target analyte can be accomplished on demand by using, for example, surface-activated magnetic beads. These magnetic beads are capable of binding a number of different ligands, such as antibodies, carbohydrates, and nucleic acids, which can be particularly chosen based on known ligand-analyte interactions. Moreover, once the desired ligand is selected, the steps required to conjugate the ligand to the magnetic beads (e.g., through covalent linkage of the ligand to the surface of the beads) are relatively trivial and can be accomplished on site by any competent technician using standard laboratory equipment. In effect, this versatility can transform known molecular interactions and old techniques into an effective way of quickly and easily isolating a target analyte from solution.

[0045] Moreover, many of the magnetic bead manufacturers have optimized bead production and are capable of producing and reproducing magnetic beads that have the same (or substantially similar) size, surface area, iron content, and magnetic mobility. This has resulted in a meaningful reduction of batch-to-batch variations and has allowed for more consistent performance from the product, itself. Nevertheless, known systems and methods of magnetically isolating and/or enriching target analytes from a sample rely on manual processing steps that are prone to error and inconsistency. Even if each operator follows a strict protocol in an attempt to ensure some level of batch-to-batch consistency, it is difficult for an operator, or multiple operators, to achieve identical results or even to validate that each step of the protocol was performed in substantially the same manner and with substantially the same timing. Thus, regardless of how consistent or uniform the magnetic beads are manufactured, the manual nature of magnetic bead isolation protocols and their attendant equipment inherently introduces unwanted variation and uncertainty.

[0046] In some instances, such as in a clinical setting, it would be particularly advantageous if such variations and uncertainties could be limited or eliminated altogether. An automated system could bring reliable uniformity to the execution of each step of a given target analyte isolation protocol and thereby limit inter- and intra-experimental variations. Automated systems could also beneficially reduce uncertainties related to, among other things, the number, timing, or force associated with mixing steps in a given target analyte isolation protocol by monitoring or logging these data throughout the protocol. Together, the benefits of an automated system allow for increased quality control measures to be implemented, which can increase recovery efficiency and reduce the time and personnel costs associated with target analyte isolation and/or enrichment. It can also allow for the reliable and safe isolation of target analytes from patient samples and advance therapies in personalized medicine.

[0047] As a nonlimiting example, chimeric antigen receptor (CAR) T-cell therapy is a type of cancer immunotherapy that relies on the genetic reprogramming of a patient’s own T-cells to identify specific cancer cell antigens and to attack those cancer cells throughout the body. In order for the genetic reprogramming to occur, the T-cells must first be isolated from the patient’s body. Typically, either a whole blood sample or a leukapheresis sample is drawn from the patient and stored in a sample bag that is subsequently transferred to the laboratory for processing. The T-cells within the sample are positively selected using, for example, CD3/CD28 magnetic beads introduced into the sample bag. The purified T-cells can then be genetically modified and expanded in vitro before being reintroduced to the patient. In all, CAR T-cell therapy can take a number of weeks, and the amount of time it takes can depend, at least in part, on the efficiency of T-cell isolation from the patient sample.

[0048] Using the current magnetic bead isolation systems known in the art, an operator is responsible to manually implement each step of the protocol for isolating and purifying the T-cell population (/'.<?., the target analyte) from the sample. Any user error or inefficiency caused by the user is likely to have a downstream impact on the timeliness and efficacy of treatment for the patient actually receiving their CAR T-cells. For example, having the proper agitation can dramatically affect cell-to-bead binding. Also, the placement and strength of the magnet can affect the efficiency at which target cells are captured. If improperly placed or under powered, a portion of the target cells will not be captured and instead be washed away with the supernatant. In view of the foregoing, there is an outstanding need for automated systems that enable the magnetic isolation and/or enrichment of target analytes from a sample.

Exemplary In-Field Modification Kits

[0049] There are a number of apparatuses known in the art that can be used to implement a magnetic bead capture assay. For small volume samples, modified tube racks are often used that have a magnet disposed between two rows. Such apparatuses are generally ill suited for efficiently processing the medium-to-large volume samples that are whole blood patient samples. Further, the patient sample is often obtained and stored within a sample bag and using the smaller volume sample tubes would require transferring the sample from the sample bag to the smaller tubes, risking contamination of the sample. Alternatively, the sample bag can be processed on a manually operated magnet assembly, such as the Cell Therapy Systems™ (CTS™) Dynamag™ magnet.

[0050] Magnet assemblies, such as the CTS™ Dynamag™ magnet and the like, are specialized laboratory equipment that can be costly to acquire. Eaboratory space is also often limited. As such, it may be difficult in some circumstances to justify or afford a large capital investment to wholly replace a manually operated system for an automated one. Instead, it is often advantageous to update existing equipment with additional (or improved) features and components. Accordingly, embodiments of the present disclosure include in-field modification kits configured to convert a manually operated magnet assembly into an at least partially automated system. The disclosed infield modification kits also provide additional functionality than their manually operated derivative. For example, magnet assemblies retrofitted with the disclosed in-field modification kits can simultaneously and individually control (i) the rotational timing and angles of the magnet assembly and (ii) the vertical positioning of the secured sample bag with respect to the magnet assembly and its attendant magnetic field. The modified magnet assemblies can also be configured to execute a number of predefined and/or user-defined automated protocols for magnetic bead capture of target analytes within a sample. In some embodiments, the movement and operating characteristics of the magnet assembly can be tracked and recorded (e.g., for quality control purposes).

[0051] It should be appreciated that while the accompanying drawings generally illustrate an exemplary in-field modification kit operable to retrofit the CTS™ Dynamag™ magnet with certain automation capabilities, the principles and feature combinations illustrated and described herein can be modified to an analogous system with a reasonable expectation of success of achieving the same (or substantially similar) results.

[0052] Referring now to FIGs. 1A and IB, illustrated is an exemplary magnet assembly 100 retrofitted with an in-field modification kit of the present disclosure. FIG. 1A illustrates a front, top perspective view of the retrofitted magnet assembly 100, and FIG. IB illustrates a back top perspective view thereof. As shown, the retrofitted magnet assembly 100 retains many of the original components of the manually operated magnet assembly, including the original magnet 102 supported by an axially aligned fulcrum 104 and associated base 106. After the in-field modification kit has been applied, the retrofitted magnet assembly 100 includes a door assembly 108 configured to selectively attach to the magnet 102 via a front elevation system 110 and a rear elevation system 112. The door assembly 108 is configured to secure a sample bag and, in combination with the elevation systems 110, 112, selectively compress the sample bag against the magnet 102 during a method for magnetic isolation and/or enrichment of target analytes.

[0053] The retrofitted magnet assembly 100 additionally includes a circular reciprocation system 114 to selectively rotate the magnet 102 by engaging the fulcrum 104 of the magnet assembly 100 and applying a force in the desired rotational direction. Activation and control of the elevation systems 110, 112 and the circular reciprocation system 114 for executing automated protocols of magnetic isolation and/or enrichment of target analytes is performed by the valve manifold 116, included as a component of the in-field modification kit. In some embodiments, the valve manifold 116 includes or is in communication with a controller for operating the elevation systems and circular reciprocation system. For example, the controller can switch the one or more valves within the valve manifold by applying voltage to the various valves. By way of example, and not limitation, automated protocols can beneficially enable an operator to cause any of the following to occur at any time and within any sequence: (1) statically hold the sample bag positionally away from the magnet (e.g., by extending the front and rear elevation systems); (2) hold the sample bag positionally away from the magnet and rock the sample bag back and forth e.g., by extending the front and rear elevation systems and engaging the circular reciprocation system to rotate the magnet); (3) press the sample bag against the magnet and rock the sample bag back and forth (e.g., by retracting the front and rear elevation systems and engaging the circular reciprocation system to rotate the magnet); (4) press the sample bag against the magnet without rocking the sample bag; and (5) various rocking modes to achieve a desired effect, such as mixing, washing, incubating, and/or draining (e.g., by selectively engaging the elevation systems and circular reciprocation system at defined intervals).

[0054] In order for the disclosed elevation systems and circular reciprocating systems to reliably and safely execute the foregoing (and other) automated protocols, these components should ideally be stably secured to the magnet assembly. The in-field modification kits of the present disclosure are preferably constructed to fit with and/or attach to existing structures of the magnet assembly. In doing so, the various components of the retrofit design can be easily and quickly installed with common tools (e.g., screwdriver and hex key) and without, for example, the need to drill new holes or weld components together. For example, the elevation assemblies can be secured to the magnet using the same threaded mounts originally used to secure the front and rear handles for manually tilting the magnet. Similarly, the circular reciprocation system can be mounted at the location where the angle measurement plate was originally installed.

[0055] Although the retrofitted magnet assembly 100 of FIGs. 1A and IB is shown as having a front elevation system and a rear elevation system, it should be appreciated that in some embodiments, in-field modification kits include a single elevation system (e.g., either a front elevation system or a rear elevation system). In such embodiments, the door assembly can be pivotally mounted to a first side of the magnet assembly and have the elevation system associated with a second, opposite side of the magnet assembly. [0056] Referring now to FIGs. 2A-2C, illustrated are various views of the door assembly 108, which is included as one component of the in-field modification kits disclosed herein. The door assembly 108 includes a door body 118 extending between a proximal portion 120 and a distal portion 122 and is configured to secure a sample bag (not shown) to an underside of the door body 118. Sample bags typically comprise two sheets of heavy plastic that have been sealed together at their peripheral edges. Generally, a flap is formed at a proximal edge of the sample bag and includes an inlet port and an outlet port that each communicate with the interior cavity of the bag. The ports are typically tubular members to which an elongated flexible tube can be attached for transferring fluid into and/or out of the sample bag. Normally at a distal end of the sample bag, an aperture extends through the sealed layers of heavy plastic and facilitates hanging of the sample bag.

[0057] The door body 118 is shaped to accommodate standard sample bags and to facilitate an even compression across the volume of the sample bag when secured to the magnet 102. In an exemplary use, the sample bag is initially associated with the underside of the door body 118 by hanging the sample bag by the bag’s distal aperture on hanger element 124. As shown, the hanger element 124 is located at the distal portion 122 of the door body 118 and is shaped to form a Ilshaped channel between the body thereof and the underside of the door body 118. In some embodiments, the shape of the hanger element may be different but, nevertheless, would preferably be configured to secure the sample bag at a distal end of the door body.

[0058] The hanger element 124 can be a component part of a spring system 126 formed into the rear pivot 128 that is fastened to the distal portion 122 of the door body 118. The hanger element 124 can be associated with the spring system 126 and span the depth of the door body 118, extending beyond the underside of the door body 118 where it can engage the distal aperture of a sample bag. The hanger element 124 can be configured to slide within a channel formed by the door body 118 such that movement of the hanger element 124 toward the proximal portion 120 of the door body 118 compresses a spring within the spring system 126. Once attached to the hanger element 124, the sample bag can be secured to the door body 118 using any of the plurality of fasteners 130 disposed at the proximal portion 120 of the door body 118. In some embodiments, the plurality of fasteners 130 are positioned on the underside of the door body 118 to correspond with apertures formed into the proximal end of the sample bag. Once the sample bag is secured by the fasteners 130, the hanger element 124 can be released, causing the hanger element 124 to be biased away from the proximal portion 120 of the door body 118 by the spring system 126 (e.g., as the spring decompresses) to pull the sample bag taut between the fasteners 130 and the hanger element 124.

[0059] As perhaps best shown in the side view of FIG. 2B, some embodiments of the door assembly are configured such that the only elements proud of the underside of the door body 118 are the fasteners 130 and the hanger element 124. This can beneficially allow the door body 118 to compress the associated bag between the door body and the magnet to a desired distance without interference. In some instances, the desired distance is determined by the effective magnetic field produced by the magnet. For example, if the magnet produces an effective magnetic field 8 mm above the surface of the magnet, compressing the sample bag between the door body and the magnet such that the space therebetween is 8 mm or less can ensure that any magnetic beads within the contents of the sample bag are affected by the magnetic field and drawn against the surface of the sample bad closest to the magnet. It should be appreciated, therefore, that the fasteners and hanger element can be adjusted e.g., shortened or lengthened) proportionally to the strength of the magnet and the distance of its effective magnetic field.

[0060] As discussed briefly above, many sample bags are fitted with inlet and outlet ports. These ports are typically tubular in shape and resistant to plastic deformation (i.e., made of a material that is characterized by a high Young’s modulus), which may interfere with an even compression of the bag contents and/or may prevent compression of the sample bag to within the desired distance of the magnet. To prevent interference of the inlet and outlet ports with the capture of the magnetic beads, recesses 132 can be formed into the proximal end of the door body 118 and sized and shaped to accommodate the inlet and outlet ports of the sample bag. In some embodiments, such as that shown in FIGs. 2A-2C, the depth of each recess 132 is a fractional amount of the total thickness of the door body 118. In some embodiments, the recesses are formed through the entire thickness of the door body, to essentially form through channels within the door body.

[0061] In some embodiments, it may be useful for operators to be able to view or monitor the contents of the sample bag as different automated protocols are performed. Accordingly, the door body can be made of or include a transparent or translucent material. In some embodiments, the door body is made of polycarbonate or other robust plastic or glass that can withstand chemical sterilization (e.g., cleaning between samples) and the compressive forces applied by the elevation systems.

[0062] With continued reference to FIGs. 2A-2C, the door assembly 108 can include a rear door pivot 128 fastened to a distal portion 122 of the door body 118 configured to associate the door assembly 108 with the rear elevation system 112. The rear door pivot 128 can include or otherwise form a pair of brackets 134 extending away from the distal portion 122 of the door body 118 and separated by a rod 136 spanning a space between the pair of brackets 134. The rod can be received by the rear elevation system (as shown in FIGs. 1A and IB) and allow the door assembly 108 to pivot between open and closed positions, hinging at the rear door pivot 128.

[0063] The door assembly 108 can additionally include a front door pivot 138 fastened to the proximal portion 120 of the door body 118 and configured to associate the door assembly 108 with the front elevation system 110. The front door pivots 138 of FIGs. 2A-2C include a bracket secured to the proximal portion 120 of the door body 118 and that retains a corresponding dowel 140 for securing the door body 118 in a closed position with respect to the magnet. As shown, the dowel 140 is oriented toward the longitudinal axis of the door body 118 and into a void space formed between two opposing arms of the door body. This particular orientation and structure engages complementary structures on the front elevation system. Accordingly, the orientation and structure of the front door pivot can be different in some embodiments while maintaining the desired functionality of the front door pivot illustrated and described herein.

[0064] The front door pivot 138 can additionally include one or more tube routing features 142. The tube routing features 142 can be formed into the body of the front door pivot 138 or may be coupled thereto. The tube routing features 142 are configured to direct consumable tubing associated with inlet or outlet ports away from the door assembly 108 and to prevent the consumable tubing from getting pinched between the door body and the magnet when the elevation system is engaged and compressing the sample bag therebetween.

[0065] It should be appreciated that other configurations and structures of the front and/or rear door pivot(s) can provide the same or similar function as the embodiment shown and described in FIGs. 2A-2C; such configurations and alternative structures are envisioned within the scope of this disclosure.

[0066] The door assemblies of the present disclosure, such as those embodiments described above, are configured to be engaged by front and rear elevation systems e.g., as shown in FIGs. 1A and IB) and thereby selectively adjust the distance between the door assembly and the magnet. In doing so, the contents of the sample bag can be selectively drawn into and out of the effective magnetic field of the magnet. In some embodiments, the front and rear elevation systems are configured to fire in unison, thereby drawing each portion of the sample bag into and out of the magnetic field of the magnet at the same time.

[0067] FIGs. 3A-3C illustrate various views of a front elevation system 110 in accordance with one or more embodiments of the present disclosure. As shown, the front elevation system 110 is configured to engage the front door pivots of the door assembly and to move the door body in cooperation with the rear elevation system 112. The front elevation system 110 is secured to a proximal face of the magnet by an actuator mount 144. In some embodiments, a handle associated with the proximal face of the magnet can be removed, and the actuator mount 144 can be secured to the magnet using the mounting features present at the proximal face for originally securing the handle. For example, threaded holes in the proximal face of the magnet can be originally used to secure a handle. After removing the handle, the actuator mount 144 can be secured to the proximal face of the magnet using threaded bolts 146 sized and shaped to fit the complementary threaded holes in the magnet. It should be appreciated that the actuator mount included within various infield modification kits of the present disclosure can be modified (e.g., in size, shape, or mounting feature used to secure the actuator mount to the magnet) such that it secures to a corresponding magnet, preferably without having post manufacturing structural modifications made to the magnet and/or magnet assembly e.g., drilling holes or welding components to the face of the magnet or to the base supporting the magnet).

[0068] With continued reference to FIGs. 3A-3C, the front elevation system can include a linear actuator 148 having a stationary body 150 and a movement arm 152. The stationary body 150 can be coupled to the actuator mount 144 such that the stationary body 150 is anchored in place (relative to the magnet), and activation of the linear actuator 148 causes the movement arm 152 to move relative to the stationary body 150. The movement arm 152 is configured to interact with the front door pivot and thereby cause the proximal portion of the door assembly to move in unison with the movement arm 152. In some embodiments, the interaction between the movement arm 152 of the linear actuator 148 and the front door pivot 138 is mediated by an actuator block 154. The actuator block 154 can be secured to the movement arm 152 at a first end thereof and have a channel 156 formed in the opposite end that is sized and shaped to receive the dowel (or other engagement feature) of the front door pivot 138.

[0069] The front elevation system 110 can additionally include a doorknob 158 that is secured to, and rotatable about, the actuator block 154 and configured to secure the front elevation system 110 to the door body 118 when the door body 118 is in a closed position. In some embodiments, the doorknob 158 can include a slot 160 formed therein that is oriented, sized, and shaped to receive the corresponding dowel of the front door pivot 138 such that when the corresponding dowel is passed through the slot 160 and into the axially-aligned channel 156 formed in the actuator block 154, misalignment of the slot 160 with the dowel-filled channel 156 secures the door body 118 in the closed position with respect to the magnet. In this closed configuration, the proximal portion of the door assembly can be moved toward or away from the magnet by engaging the linear actuator 148.

[0070] The front elevation system can additionally include a tube routing block 162, which can beneficially prevent pinching of any tubes associated with the sample bag as the sample bag is moved toward and/or away from the magnet. For example, a sample bag may include a consumable tube associated with the inlet port for transferring solution into the sample bag during a magnetic bead isolation and/or enrichment protocol. Another consumable tube can be associated with the outlet port for draining solution from the sample bag. In some embodiments, the tube routing block 162 can include a pair of tube routing features 164 formed on opposing sides of the tube routing block 162. The pair of tube routing features 164 can secure the consumable tubing associated with the inlet and outlet ports and prevent it from being pinched or snagged by the front elevation system as the sample bag is manipulated during magnetic bead capture. In some embodiments, the tube routing block includes an additional tube routing feature 166 formed therein that is oriented in a direction transverse to the pair of tube routing features 164. This additional tube routing feature 166 can, for example, guide consumable tubing around the front elevation system and similarly prevent it from being pinched or tangled thereby.

[0071] In some embodiments, the linear actuator 148 is a pneumatic cylinder. The pneumatic cylinder can include press-fit connectors 168 (or other suitable connectors) for connecting the pneumatic cylinder to a pressurized air source. In some embodiments, the linear actuator is an electric linear actuator. In such embodiments, the press-fit connectors 168 can be substituted for the appropriate electrical connectors for powering the electric linear actuator. [0072] Referring now to FIGs. 4A-4C, various views of a rear elevation system 112 are illustrated in accordance with one or more embodiments of the present disclosure. As shown, the rear elevation system 112 is configured to engage the rear door pivots of the door assembly and to move the door body 118 in cooperation with the front elevation system 110.

[0073] Similar to the front elevation system 110 described above, the rear elevation system 112 can be secured to a distal face of the magnet by a rear actuator mount 170. A handle associated with the distal face of the magnet can be removed, and the rear actuator mount 170 can be secured to the magnet using the mounting features present at the distal face for originally securing the handle. For example, threaded holes in the distal face of the magnet that were originally used to secure a handle can be used to secure the rear actuator mount 170 to the distal face of the magnet. As with the actuator mount 144 of the front elevation system 110, threaded bolts 172 that are sized and shaped to fit the complementary threaded holes in the distal face of the magnet can be used to secure the rear actuator mount 170. It should be appreciated that the rear actuator mount included within various in-field modification kits of the present disclosure can be modified (e.g., in size, shape, or mounting feature used to secure the rear actuator mount to the magnet) such that it secures to a corresponding magnet, preferably without having post manufacturing structural modifications made to the magnet and/or magnet assembly e.g., drilling holes or welding components to the face of the magnet or to the base supporting the magnet).

[0074] The rear elevation system 112 can include a rear linear actuator 174 having a rear stationary body 176 and a rear movement arm 178. The rear stationary body 176 can be coupled to the rear actuator mount 170 such that the rear stationary body 176 is anchored in place (relative to the magnet), and activation of the rear linear actuator 174 causes the rear movement arm 178 to move relative to the rear stationary body 176. The rear movement arm 178 is configured to interact with the rear door pivot 128 and thereby cause the distal portion of the door assembly to move in unison with the rear movement arm 178. In some embodiments, the interaction between the rear movement arm 178 of the rear linear actuator 174 and the rear door pivot 128 is mediated by a rear actuator block 180. The rear actuator block 180 can be secured to the rear movement arm 178 at a first end thereof and have a slot 182 formed into the rear actuator block 180 for securing the rear elevation system 112 to the door body 118. In some embodiments, the slot 182 is sized and shaped to receive the rod (e.g., element 136 of FIG. 2C) of the rear door pivot 128 and allow rotational movements of the door assembly with respect to the rear elevation system 112 while maintaining the ability of the rear elevation system to move the door assembly vertically. Thus, although the front and rear elevation systems may be configured to travel up and down in unison, the slot design of the rear actuator block 180 can enable independent travel of the two systems without jamming or otherwise causing an issue with their movement.

[0075] In some embodiments, the rear linear actuator 174 is a pneumatic cylinder. The pneumatic cylinder can include press-fit connectors 184 (or other suitable connectors known in the art such as barb fittings or Luer fittings) for connecting the pneumatic cylinder to a pressurized air source. In some embodiments, the linear actuator is an electric linear actuator. In such embodiments, the press-fit connectors 184 can be substituted for the appropriate electrical connectors for powering the electric linear actuator.

[0076] In-field modification kits of the present disclosure can additionally include a circular reciprocation system 114, as shown in greater detail within FIGs. 5A and 5B, for selectively tilting the magnet 102 and door assembly (and any sample bag) associated therewith. In some embodiments, the circular reciprocation system 114 includes a rotary actuator 186 comprised of a housing 188 and a rotating element 190. The rotary actuator can have a wide range of rotational motion that, in some embodiments, can be easily adjusted manually (e.g., using a wrench) and can include dampers to allow for smooth transitions between states.

[0077] The circular reciprocation system 114 can additionally include an anchor assembly for securing the rotary actuator 186 to the fulcrum 104 of a corresponding magnet 102 and/or to a stand supporting the fulcrum 104 such that a rotational force exerted by the rotary actuator 186 is transferred to the fulcrum 104 and/or magnet 102. In some embodiments, the anchor assembly includes an anchor mount 192 for securing the rotary actuator housing to the stand supporting the fulcrum 104. The anchor mount 192 can be secured to any portion of the stand or other support device, preferably using preexisting mounting features. In some embodiments, the anchor mount 192 is secured to the stand using, for example, screws 194 in the location where an angle measurement plate was originally installed.

[0078] The anchor assembly can additionally include an actuator interface 196 configured to engage the rotating element 190 of the rotary actuator 186. In some embodiments, the actuator interface 196 includes a face plate that couples to the rotating element 190 of the rotary actuator 186 and a central post 198 that extends away from the face plate. The central post can span a bushing 200 and engage a force plate 202. In some embodiments, the central post 198 includes a flattened side 204 (or other engagement feature) that is sized and shaped to mate with a complementary engagement feature 206 formed by the force plate 202, thereby enabling interaction — and force transfer — between the rotary actuator 186 and the fulcrum 104 and/or magnet 102. In some embodiments, the additionally includes a boss that can engage the magnet and assist the force plate in transferring force from the rotary actuator to the magnet.

[0079] In some embodiments, the in-field modification kit can additionally include a sensor 208 that can be selectively associated with the housing of the rotary actuator. The sensor can be used to monitor the activity (e.g., rotation angle and/or number of rotations) of the rotary actuator, to monitor the solution going into and/or out of the solution bag e.g., a bubble sensor), or the like. [0080] As shown in FIGs. 5 A and 5B, the rotary actuator is a pneumatic rotary actuator having press-fit connectors 210 (or other suitable connectors) for connecting the pneumatic rotary actuator to a pressurized air source. In some embodiments, the rotary actuator is a stepper motor. In such embodiments, the press-fit connectors 210 can be substituted for the appropriate electrical connectors for powering/driving the stepper motor.

[0081] A common sample known and used in the art is illustrated in FIG. 6A. These sample bags include an inlet port 212 and an outlet port 214 with a sealed wall 216 formed between the two. This configuration encourages better bead capture from the solution entering the sample bag, as it is prevented from immediately exiting the bag via outlet port 214. Further, the flow of solution (as shown by the arrows in FIG. 6A) causes the magnetic beads within the sample bag to move in perpendicular (or at the very least transverse) directions as they are being washed/processed by the solution. This increases the likelihood that the magnetic beads will be captured by the magnetic field.

[0082] In some embodiments, the in-field modification kits disclosed herein can include a door body having extensions or protrusions on the underside thereof. When the elevation systems compress the solution bag against the magnet, the protrusions on the door body can from fluid tight junctions in a desired pattern (e.g., as shown in FIG. 6B). For example, the protrusions can be arranged to cause the junctions 218 to form. These newly formed junctions 218 can redirect the flow of solution (e.g., cell culture, wash solution, or similar) through the sample bag causing it to change directions and consequently increase the likelihood that the magnetic beads will be captured by the magnetic field of the magnet. By having the door body generate the flow pattern within the sample bag when compressed by the elevation systems, complex sample bag manufacturing can be avoided. Additionally, when the elevation system moves the bag away from the magnet, the complex flow pattern is removed, and the solution within the sample bag can be better mixed and/or drained.

[0083] Referring now to FIG. 7, in-field modification kits of the present disclosure can include a valve manifold 116 operably connected to the elevation systems 110, 112 and to the circular reciprocation system 114 and can be configured to execute automated protocols of magnetic isolation and/or enrichment of target analytes (e.g., in communication with a controller or similar). As shown, the valve manifold 116 can connect to a pressurized air system 220 on site and selectively control the pneumatic linear and rotary actuators. Additionally, or alternatively, the valve manifold can be connected to a power source for selectively operating electric linear actuators and/or stepper motors.

[0084] As also illustrated in FIG. 7, the valve manifold can be electronically coupled to a computer system 300 for programming the manifold or associated controller and/or for managing the operations of the automated magnetic assembly following retrofitting with the in-field modification kits disclosed herein. It will be appreciated that in this description and in the claims, the term “computer system” or “computing system” is defined broadly as including any device or system — or combination thereof — that includes at least one physical and tangible processor 302 and a physical and tangible memory 304 capable of having stored thereon computer-executable instructions that may be executed by a processor 302. By way of example, not limitation, the term “computer system” or “computing system,” as used herein is intended to include personal computers, desktop computers, laptop computers, tablets, hand-held devices (e.g., mobile telephones, PDAs, pagers), microprocessor-based or programmable consumer electronics, minicomputers, mainframe computers, multi-processor systems, network PCs, distributed computing systems, datacenters, message processors, routers, and switches.

[0085] The memory 304 may take any form and may depend on the nature and form of the computing system. The memory 304 can be physical system memory, which includes volatile memory, non-volatile memory, or some combination of the two. The term “memory” may also be used herein to refer to non-volatile mass storage such as physical storage media, which can also be referred to as hardware storage devices.

[0086] The computing system also has thereon multiple structures often referred to as an “executable component.” For instance, the memory 304 of computing system 300 can include an executable component for operating the controller and/or functions of the elevation systems and/or circular reciprocation systems disclosed herein. The term “executable component” is the name for a structure that is well understood to one of ordinary skill in the art in the field of computing as being a structure that can be software, hardware, or a combination thereof.

[0087] For instance, when implemented in software, one of ordinary skill in the art would understand that the structure of an executable component may include software objects, routines, methods, and so forth, that may be executed by one or more processors on the computing system, whether such an executable component exists in the heap of a computing system, or whether the executable component exists on computer-readable storage media. The structure of the executable component exists on a computer-readable medium in such a form that it is operable, when executed by one or more processors of the computing system, to cause the computing system to perform one or more functions, such as the functions and methods described herein. Such a structure may be computer-readable directly by a processor — as is the case if the executable component were binary. Alternatively, the structure may be structured to be interpretable and/or compiled — whether in a single stage or in multiple stages — so as to generate such binary that is directly interpretable by a processor.

[0088] The term “executable component” is also well understood by one of ordinary skill as including structures that are implemented exclusively or near-exclusively in hardware logic components, such as within a field programmable gate array (FPGA), an application specific integrated circuit (ASIC), Program- specific Standard Products (ASSPs), System-on-a-chip systems (SOCs), Complex Programmable Logic Devices (CPLDs), or any other specialized circuit. Accordingly, the term “executable component” is a term for a structure that is well understood by those of ordinary skill in the art of computing, whether implemented in software, hardware, or a combination thereof.

[0089] The terms “component,” “service,” “engine,” “module,” “control,” “generator,” or the like may also be used in this description. As used in this description and in this case, these terms — whether expressed with or without a modifying clause — are also intended to be synonymous with the term “executable component” and thus also have a structure that is well understood by those of ordinary skill in the art of computing.

[0090] While not all computing systems require a user interface, in some embodiments a computing system includes a user interface for use in communicating information from/to a user. For example, a user interface can be used by a user to dictate their desired operation of the modified magnet assembly. The user interface may include output mechanisms as well as input mechanisms (e.g., VO Devices 306). The principles described herein are not limited to the precise output mechanisms or input mechanisms as such will depend on the nature of the device. However, output mechanisms might include, for instance, speakers, displays, tactile output, projections, holograms, and so forth. Examples of input mechanisms might include, for instance, microphones, touchscreens, projections, holograms, cameras, keyboards, stylus, mouse, or other pointer input, sensors of any type, and so forth.

[0091] Accordingly, embodiments described herein may comprise or utilize a special purpose or general-purpose computing system. Embodiments described herein also include physical and other computer-readable media for carrying or storing computer-executable instructions and/or data structures. Such computer-readable media can be any available media that can be accessed by a general purpose or special purpose computing system. Computer-readable media that store computer-executable instructions are physical storage media. Computer-readable media that carry computer-executable instructions are transmission media. Thus, by way of example — not limitation — embodiments disclosed or envisioned herein can comprise at least two distinctly different kinds of computer-readable media: storage media and transmission media.

[0092] Computer-readable storage media include RAM, ROM, EEPROM, solid state drives (“SSDs”), flash memory, phase-change memory (“PCM”), CD-ROM or other optical disk storage, magnetic disk storage or other magnetic storage devices, or any other physical and tangible storage medium that can be used to store desired program code in the form of computer-executable instructions or data structures and that can be accessed and executed by a general purpose or special purpose computing system to implement the disclosed functionality of the invention. For example, computer-executable instructions may be embodied on one or more computer-readable storage media to form a computer program product. For the absence of doubt, such computer-readable storage media can also be termed “hardware storage devices,” which are physical storage media — not transmission media.

[0093] Transmission media can include a network and/or data links that can be used to carry desired program code in the form of computer-executable instructions or data structures and that can be accessed and executed by a general purpose or special purpose computing system. Combinations of the above should also be included within the scope of computer-readable media. [0094] Further, upon reaching various computing system components, program code in the form of computer-executable instructions or data structures can be transferred automatically from transmission media to storage media (or vice versa). For example, computer-executable instructions or data structures received over a network or data link can be buffered in RAM within a network interface module (e.g., a “NIC”) and then eventually transferred to computing system RAM and/or to less volatile storage media at a computing system. Thus, it should be understood that storage media can be included in computing system components that also — or even primarily — utilize transmission media.

[0095] Those skilled in the art will further appreciate that a computing system may also contain communication channels 308 that allow the computing system to communicate with other computing systems over, for example, a network. Accordingly, the methods described herein may be practiced in network computing environments with many types of computing systems and computing system configurations. The disclosed methods may also be practiced in distributed system environments where local and/or remote computing systems, which are linked through a network 310 (either by hardwired data links, wireless data links, or by a combination of hardwired and wireless data links), both perform tasks. In a distributed system environment, the processing, memory, and/or storage capability may be distributed as well.

[0096] Various alterations and/or modifications of the inventive features illustrated herein, and additional applications of the principles illustrated herein, which would occur to one skilled in the relevant art and having possession of this disclosure, can be made to the illustrated embodiments without departing from the spirit and scope of the invention as defined by the claims, and are to be considered within the scope of this disclosure. Thus, while various aspects and embodiments have been disclosed herein, other aspects and embodiments are contemplated. While a number of methods and components similar or equivalent to those described herein can be used to practice embodiments of the present disclosure, only certain components and methods are described herein. [0097] It will also be appreciated that systems, devices, products, kits, methods, and/or processes, according to certain embodiments of the present disclosure may include, incorporate, or otherwise comprise properties or features (e.g., components, members, elements, parts, and/or portions) described in other embodiments disclosed and/or described herein. Accordingly, the various features of certain embodiments can be compatible with, combined with, included in, and/or incorporated into other embodiments of the present disclosure. Thus, disclosure of certain features relative to a specific embodiment of the present disclosure should not be construed as limiting application or inclusion of said features to the specific embodiment. Rather, it will be appreciated that other embodiments can also include said features, members, elements, parts, and/or portions without necessarily departing from the scope of the present disclosure.

[0098] Moreover, unless a feature is described as requiring another feature in combination therewith, any feature herein may be combined with any other feature of a same or different embodiment disclosed herein. Furthermore, various well-known aspects of illustrative systems, methods, apparatus, and the like are not described herein in particular detail in order to avoid obscuring aspects of the example embodiments. Such aspects are, however, also contemplated herein.

[0099] The present disclosure may be embodied in other specific forms without departing from its spirit or essential characteristics. The described embodiments are to be considered in all respects only as illustrative and not restrictive. The scope of the invention is, therefore, indicated by the appended claims rather than by the foregoing description. While certain embodiments and details have been included herein and in the attached disclosure for purposes of illustrating embodiments of the present disclosure, it will be apparent to those skilled in the art that various changes in the methods, products, devices, and apparatus disclosed herein may be made without departing from the scope of the disclosure or of the invention, which is defined in the appended claims. All changes which come within the meaning and range of equivalency of the claims are to be embraced within their scope.

Claims

1. An in-field modification kit configured to convert a manually operated magnet assembly to an at least partially automated system, the in-field modification kit comprising: a door assembly configured to selectively attach to a magnet assembly; an elevation system configured to secure to the magnet assembly and to engage at least a portion of the door assembly for selectively adjusting a distance between the door assembly and the magnet assembly; a circular reciprocation system configured to engage a fulcrum of the magnet assembly and to selectively rotate the magnet assembly; and a valve manifold operably connected to the elevation system and the circular reciprocation system for executing automated protocols of magnetic isolation and/or enrichment of target analytes.

2. The in-field modification kit of claim 1, wherein the door assembly comprises: a door body; a front door pivot fastened to a proximal portion of the door body; and a rear door pivot fastened to a distal portion of the door body.

3. The in-field modification kit of claim 2, wherein the rear door pivot comprises a pair of brackets fastened to the distal portion of the door body and separated by a rod spanning a space between the pair of brackets.

4. The in-field modification kit of claim 2 or claim 3, wherein the front door pivot comprises one or more brackets fastened to the proximal portion of the door body, the one or more brackets retaining a corresponding dowel for securing the door body in a closed position with respect to the magnet assembly.

5. The in-field modification kit of any one of claims 2-4, wherein the front door pivot comprises one or more tube routing features.

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6. The in-field modification kit of any one of claims 2-6, wherein the door assembly comprises a plurality of fasteners for securing a sample bag to an underside of the door body.

7. The in-field modification kit of any one of claims 1-6, wherein the elevation system comprises a front elevation system configured to be secured to a proximal face of the magnet assembly and to engage the proximal portion of the door body.

8. The in-field modification kit of claim 7, wherein the front elevation system comprises: a linear actuator comprising a stationary body and a movement arm; an actuator mount for securing the stationary body to the proximal face of the magnet assembly; and an actuator block secured to a proximal end of the movement arm.

9. The in-field modification kit of claim 8, wherein the front elevation system comprises a doorknob secured to, and rotatable about, the actuator block, for securing the front elevation system to the door body when the door body is in a closed position.

10. The in-field modification kit of claim 9, wherein the doorknob comprises a slot formed therein that is oriented, sized, and shaped to receive the corresponding dowel of the front door pivot such that when the corresponding dowel is passed through the slot and into an axially-aligned channel formed in the actuator block, misalignment of the slot with the dowel secures the door body in the closed position with respect to the magnet assembly.

11. The in-field modification kit of any one of claims 7-10, wherein the front elevation system comprises a tube routing block selectively securable to the stationary body of the linear actuator.

12. The in-field modification kit of claim 11, wherein the tube routing block comprises a pair of tube routing features formed therein, each of the pair of tube routing features being positioned on opposing sides of the tube routing block in a direction substantially parallel to a movement direction of the movement arm.

13. The in-field modification kit of claim 12, wherein the tube routing block comprises an additional tube routing feature formed therein, the additional tube routing feature oriented in a direction transverse to the pair of tube routing features.

14. The in-field modification kit of any one of claims 8-13, wherein the linear actuator of the front elevation system comprises a pneumatic cylinder or an electric linear actuator.

15. The in-field modification kit of any one of claims 2-14, further comprising a rear elevation system configured to be secured to a distal face of the magnet assembly and to engage a distal portion of the door body.

16. The in-field modification kit of claim 15, wherein the rear elevation system comprises: a rear linear actuator comprising a rear stationary body and a rear movement arm; a rear actuator mount for securing the rear stationary body to the distal face of the magnet assembly; and a rear actuator block secured to a proximal end of the rear movement arm.

17. The in-field modification kit of claim 16, wherein the rear elevation system comprises a slot formed into the rear actuator block for securing the rear elevation system to the door body.

18. The in-field modification kit of claim 17, wherein the slot is sized and shaped to receive the rod of the rear door pivot.

19. The in-field modification kit of any one of claims 16-18, wherein the linear actuator of the rear elevation system comprises a pneumatic cylinder or an electric linear actuator.

20. The in-field modification kit of any one of claims 1-18, wherein the circular reciprocation system comprises: a rotary actuator comprising a housing and a rotating element; and an anchor assembly for securing the rotary actuator to the fulcrum and/or to a stand supporting the fulcrum such that rotational force exerted by the rotary actuator is transferred to the fulcrum and/or magnet assembly.

21. The in-field modification kit of claim 20, wherein the anchor assembly comprises: an anchor mount for securing the housing to the stand supporting the fulcrum; an actuator interface secured to the rotating element of the rotary actuator and having an engagement feature on a central post extending therefrom; and a force plate having a complementary engagement feature configured to mate with the engagement feature of the central post and transfer force from the rotary actuator to the fulcrum and/or magnet assembly.

22. The in-field modification kit of claim 21, wherein the force plate additionally includes a boss for assisting the force plate in transferring force from the rotary actuator to the magnet assembly.

23. The in-field modification kit of claim 21 or claim 22, further comprising a sensor selectively associated with the housing of the rotary actuator.

24. The in-field modification kit of claim 23, wherein the sensor comprises a bubble sensor.

25. The in-field modification kit of any one of claims 20-24, wherein the rotary actuator is a pneumatic rotary actuator or a stepper motor.

26. The in-field modification kit of any one of claims 1-25, wherein at least a portion of the door assembly is made of or includes a transparent material.

27. The in-field modification kit of claim 26, wherein the transparent material comprises polycarbonate or glass.

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28. The in-field modification kit of claim 14 or claim 25, wherein the elevation system comprises a pneumatic cylinder, wherein the circular reciprocation system comprises a pneumatic rotary actuator, and wherein the valve manifold comprises a port for receiving pressurized air for selectively powering the pneumatic cylinder and the pneumatic rotary actuator.

29. A method for magnetic isolation and/or enrichment of target analytes, comprising processing a sample bag containing the target analyte and target- analyte specific magnetic beads on an analyte isolation and/or enrichment system retrofitted with the in-field modification kit of any one of claims 1-28.

30. An automated system for magnetic isolation and/or enrichment of target analytes, comprising: an analyte isolation and/or enrichment system retrofitted with the in-field modification kit of any one of claims 1-28; and a computer system in electrical communication with the valve manifold, the computer system comprising: one or more processors; and one or more hardware storage devices having stored thereon computer executable instructions that, when executed by the one or more processors, configure the computer system to perform at least the following: initiate a predefined or user-defined protocol for isolating and/or enriching the target analyte.

31. The system of claim 30, wherein initiating the predefined or user-defined protocol comprises: activating the elevation system to compress a sample bag associated with the door assembly against the magnet assembly; and activating the circular reciprocation system to rotate the magnet and associated sample bag.

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32. The system of claim 31, wherein activating the elevation system to compress the sample bag comprises compressing the sample bag such that the contents of the bag are within the operable magnetic field of the magnet assembly.

33. The system of claim 31 or claim 32, wherein activating the circular reciprocation system causes the magnet assembly to cycle between elevated and lowered positions.

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