Magnetic assisted separation apparatus and related method

Abstract

To provide a magnetic assisted separation apparatus for separating a target substance from a medium in which a target substance is suspended, and a related method.SOLUTION: A magnetic assisted separator 10 for separating a target substance from a medium 54 in which a target substance is suspended, may include a frame 12 having a first opening configured to receive at least one container, the at least one container 20 containing the medium; and a first magnetic field generating element 14 and a second magnetic field generating element 16 mounted on opposing sides of the frame at a distance from each other such that the at least one container can be positioned between the first and second magnetic field generating elements.SELECTED DRAWING: Figure 4

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS Priority is claimed to U.S. Provisional Patent Application No. 62 / 534,563, filed July 19, 2017, the entire contents of which are incorporated herein by reference.

[0002] The present disclosure relates generally to separation devices and methods, and more particularly to separating target materials, such as biomolecules, from a fluid medium in which they are suspended to facilitate downstream processing or analysis of the target materials. [Background technology]

[0003] Certain diagnostic, research, and drug manufacturing activities benefit from or require the isolation of target substances, such as proteins, contained in cell cultures or other biological mixtures. This task has been accomplished in the past by a variety of techniques. Some of these require altering the solubility of the target substance so that it precipitates from the biological mixture. Certain other techniques require centrifugation, which separates particles of different densities by spinning them at high speeds around a fixed point. Still other techniques are based on chromatography, which requires passing a biological mixture through a filter material in which the components of the biological mixture move at different speeds.

[0004] These traditional purification techniques, and others, tend to be time consuming, labor intensive, and / or limited to relatively small sample sizes. For example, centrifugation is typically performed in test tubes or bottles, which may limit the amount of material that can be processed at a given time. Also, some traditional purification techniques may require laboratory technicians to manually pipette fluids between various containers, which can be inefficient and may increase the risk of cross-contamination.

[0005] The present disclosure describes purification-related apparatus and methods that embody advantageous alternatives to existing purification apparatus and methods and that may address one or more of the problems or needs described herein, as well as provide other benefits and advantages. Summary of the Invention [Means for solving the problem]

[0006] One aspect of the present disclosure provides a magnetic separator for separating or removing target materials from a medium in which the target materials are suspended. The magnetic separator may include a frame having a first opening configured to receive at least one container or vessel containing the medium. The magnetic separator may also include a first magnetic field generating element and a second magnetic field generating element. The first magnetic field generating element and the second magnetic field generating element may be mounted on opposite sides of the frame at a distance from each other such that at least one vessel is positionable between the first magnetic field generating element and the second magnetic field generating element.

[0007] Another aspect of the present disclosure provides a purification method, which may include: (a) adding a medium in which a target substance is suspended to a vessel or container; (b) adding a plurality of magnetic beads to the vessel, where the target substance temporarily binds to the plurality of magnetic beads; and (c) disposing the vessel between a first magnetic field generating element and a second magnetic field generating element, where the first magnetic field generating element and the second magnetic field generating element are held at a distance from each other by a frame, and where at least one of the first magnetic field generating element or the second magnetic field generating element magnetically attracts and holds the plurality of magnetic beads against an interior surface of the vessel.

[0008] A further aspect of the present disclosure provides a workstation for separating a target substance from a medium in which the target substance is suspended. The workstation may include a work surface for receiving at least one vessel or container containing the medium, and a fluid transfer member configured to transfer fluid to and from the at least one vessel. Additionally, the workstation may include an automated manipulator configured to move the fluid transfer member relative to the work surface. Furthermore, the workstation may include a plurality of magnetic field generating elements, each movable relative to the work surface between a first position spaced apart from the at least one vessel and a second position proximate to the at least one vessel.

[0009] Yet another aspect of the present disclosure provides a purification method, the method may include: (a) providing a workstation having a work surface, an automated manipulator movable relative to the work surface and carrying a fluid transfer member, and a plurality of magnetic field generating elements spaced laterally from one another and defining a plurality of rows; (b) adding at least one medium in which a target substance is suspended to a plurality of vessels or containers; (c) adding a plurality of magnetic beads to the plurality of vessels, wherein the target substance temporarily binds to the plurality of magnetic beads; and (d) arranging the plurality of vessels within the plurality of rows defined between the plurality of magnetic field generating elements such that the plurality of magnetic field generating elements magnetically attract and hold the plurality of magnetic beads to an interior surface of each of the plurality of vessels.

[0010] The present disclosure will be more fully understood when the following description is taken in conjunction with the accompanying drawings. Some of the drawings may be simplified by omitting selected elements to more clearly show other elements. The omission of such elements in some of the drawings does not necessarily indicate the presence or absence of the particular element in any of the embodiments, unless expressly described in the corresponding written description. Additionally, none of the drawings are necessarily drawn to scale. [Brief description of the drawings]

[0011] [Figure 1] FIG. 1 is a top perspective view of one embodiment of a magnetic separator according to the principles of the present disclosure; [Diagram 2] FIG. 2 is a front perspective view of the magnetic separator shown in FIG. [Diagram 3] FIG. 2 is a rear perspective view of the magnetic separator shown in FIG. [Figure 4] FIG. 2 is a cross-sectional view of the magnetic separator shown in FIG. 1 loaded with a vessel containing a fluid medium and magnetic beads. [Diagram 5] FIG. 13 is a perspective side view of another embodiment of a magnetic separator according to the principles of the present disclosure. [Figure 6A] 1 shows a schematic chronological diagram of the steps of one embodiment of a purification method according to the principles of the present disclosure. [Figure 6B] 1 shows a schematic chronological diagram of the steps of one embodiment of a purification method according to the principles of the present disclosure. [Figure 6C] 1 shows a schematic chronological diagram of the steps of one embodiment of a purification method according to the principles of the present disclosure. [Figure 6D] 1 shows a schematic chronological diagram of the steps of one embodiment of a purification method according to the principles of the present disclosure. [Figure 6E] 1 shows a schematic chronological diagram of the steps of one embodiment of a purification method according to the principles of the present disclosure. [Figure 6F] 1 shows a schematic chronological diagram of the steps of one embodiment of a purification method according to the principles of the present disclosure. [Figure 6G] 1 shows a schematic chronological diagram of the steps of one embodiment of a purification method according to the principles of the present disclosure. [Figure 7] FIG. 1 is a schematic front plan view of one embodiment of a magnetic separation workstation according to the principles of the present disclosure; [Figure 8] FIG. 8 is a schematic side plan view of the workstation shown in FIG. [Figure 9] FIG. 1 is a front perspective view of one embodiment of a workstation according to the principles of the present disclosure; DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0012] The present disclosure generally relates to an apparatus and method for separating a target substance, such as a protein, from a fluid medium in which the target substance is suspended. In general, the apparatus and method disclosed herein include disposing one or more magnetic field generating elements in the vicinity of the exterior of one or more vessels containing a medium having the target substance. A plurality of magnetic beads may be submerged in the medium and may be bound to the target substance. The one or more magnetic field generating elements may magnetically attract the magnetic beads bound to the target substance and statically fix or hold the magnetic beads against an interior surface of the one or more vessels. The medium may then be removed from the one or more vessels, leaving behind the magnetic beads bound to the target substance. The magnetic beads may then be subjected to washing and / or elution procedures to release and / or extract the target substance from the magnetic beads. The magnetic beads may finally be separated from the magnetic field by simply moving the one or more magnetic field generating elements away from the one or more vessels (or vice versa).

[0013] Configured in this manner, the disclosed apparatus and basic methods advantageously simplify the process of separating target materials from media, and in certain embodiments can eliminate or reduce the number of manual steps that must be performed by a laboratory technician or other user. Moreover, the disclosed apparatus and methods can provide the ability to process relatively large volumes of samples without substantially increasing the workstation footprint required for purification-related equipment. Additionally, the disclosed purification apparatus and methods can reduce the possibility of cross-contamination that can occur when one or more magnetic field generating elements are submerged in the sample media.

[0014] Each of the above-mentioned components and associated methods will now be described in more detail.

[0015] The disclosed devices and methods may be used to separate various target substances (e.g., molecules, complexes of molecules, biomolecules, complexes of biomolecules, proteins, protein complexes, peptides, nucleic acid ligands, pathogenic microorganisms, cells, etc.) from various sample mixtures (e.g., cell cultures, blood, salvia, sweat, urine, feces, soil, food, etc.). Also, various magnetic beads may be used depending on the nature of the target substance to be isolated and / or the medium in which the target substance is suspended. In some embodiments, the magnetic beads may have a spherical shape and a silica-based paramagnetic core coated with a material that binds or conjugates with the target substance. The binding between the magnetic beads and the target substance may be achieved covalently, non-covalently, electrostatically, by hydrogen bonding, by van der Waals forces, and / or by any other suitable molecular binding process. In at least one embodiment, the medium may be a cell culture or other biological mixture, the target substance may be an antibody or other protein, and the magnetic beads may be protein A magnetic beads. In another embodiment, the medium may be a cell culture or other biological mixture, the target substance may be a poly-His tagged protein, and the magnetic beads may be coated with nickel, zinc, copper, or cobalt.

[0016] A non-limiting list of exemplary types of magnetic beads that can be incorporated into the purification systems and methods of the present disclosure includes affinity type magnetic beads (e.g., amine magnetic beads, aldehyde magnetic beads, carboxy magnetic beads, CDI magnetic beads, DVS magnetic beads, DADPA magnetic beads, epoxy magnetic beads, hydrazide magnetic beads, hydroxy magnetic beads, iodoacetyl magnetic beads, NHS magnetic beads, sulfhydryl magnetic beads, tosyl magnetic beads, thiol magnetic beads, silica magnetic beads, IDA magnetic beads, etc.); reverse phase type magnetic beads (e.g., C4 magnetic beads, C8 magnetic beads, C18 magnetic beads, cyanopropyl magnetic beads, phenyl magnetic beads, diphenyl magnetic beads, etc.); ion exchange type magnetic beads (e.g., DEAE magnetic beads, PSA magnetic beads, SAX magnetic beads, WCX magnetic beads, SCX magnetic beads, hydroxyapatite magnetic beads, etc.); antibody purification type magnetic beads (e.g., Protein A magnetic beads, Protein G magnetic beads, Protein A / G magnetic beads, Protein L magnetic beads, Quick IgG Pure magnetic beads, etc. , antigen peptide magnetic beads, quick IgM pure magnetic beads, anti-IgG magnetic beads, quick IgA pure magnetic beads, thiophilic magnetic beads, etc.); antibody immobilized type magnetic beads (e.g., protein A magnetic beads, protein G magnetic beads, protein A / G magnetic beads, protein L magnetic beads, epoxy-activated magnetic beads, aldehyde-terminated magnetic beads, hydrazide-terminated magnetic beads, carboxyl-terminated magnetic beads, iodoacetyl-activated magnetic beads, thiol-activated magnetic beads, etc.); recombinant protein purification type magnetic beads (e.g., Ni+-charged magnetic beads, Co+-charged magnetic beads, maltose magnetic beads, calmodulin magnetic beads, etc.); peptide immobilized type magnetic beads (e.g., epoxy-activated magnetic beads, aldehyde-terminated magnetic beads, carboxyl-terminated magnetic beads, amine-terminated magnetic beads, iodoacetyl-activated magnetic beads, thiol-activated magnetic beads, etc.); magnetic beads for DNA or RNA purification; magnetic beads for endotoxin removal; magnetic beads for abundant protein removal; and / or EDTA magnetic beads.

[0017] As used herein, the term "magnetic" is defined to include any element that is magnetic, paramagnetic, and / or ferromagnetic. Thus, magnetic beads may be magnetic beads, paramagnetic beads, ferromagnetic beads, or any combination thereof.

[0018] In some embodiments, the magnetic beads may have a density greater than that of the medium such that when the magnetic beads are submerged in a sample mixture, they sink to the bottom of a vessel holding the medium, while in other embodiments, the magnetic beads may have a density less than or equal to that of the medium such that the magnetic beads float or partially float in the medium.

[0019] 1-3 illustrate one embodiment of a magnetic separator 10 according to the principles of the present disclosure. The magnetic separator 10 generally includes a frame 12 for mounting a magnetic field generating element 14 and a magnetic field generating element 16 at a distance X1 from each other. An opening 18 may be formed in the frame 12 and sized to allow one or more containers 20 to be inserted through the opening 18 into the space between the magnetic field generating element 14 and the magnetic field generating element 16, as shown in FIG. 3. In some embodiments, the containers 20 may be mounted to or held by a non-magnetic support shelf 50 (see FIG. 4), which may also be positionable between the mounted magnetic field generating element 14 and the magnetic field generating element 16.

[0020] Generally, the frame 12 functions to maintain a separation distance X1 between the magnetic field generating element 14 and the magnetic field generating element 16, despite the existence of magnetic attraction and / or repulsion between the magnetic field generating element 14, the magnetic field generating element 16, and the magnetic beads 40 disposed in the container 20. By fixing the magnetic field generating element 14 and the magnetic field generating element 16 at a set distance X1 by the frame 12, a user may not need to set up or handle the magnetic field generating element 14 and the magnetic field generating element 16, which may be cumbersome and unsafe in a situation where the magnetic attraction between the magnetic field generating element 14 and the magnetic field generating element 16 is relatively strong. Also, by not needing to directly contact the magnetic field generating element 14 and the magnetic field generating element 16, the risk of damaging the memory or other sensitive components of the device or personal electronic device carried by the user may be reduced.

[0021] In some embodiments, the lateral distance X1 separating the first magnetic field generating element 14 and the second magnetic field generating element 16 may be within a range of about (e.g., ±10%) 3 to 36 inches, or within a range of about (e.g., ±10%) 3 to 24 inches, or within a range of about (e.g., ±10%) 3 to 18 inches, or within a range of about (e.g., ±10%) 3 to 12 inches, or about (e.g., ±10%) 1 inch or more, or about (e.g., ±10%) 2 inches or more, or about (e.g., ±10%) 3 inches or more, or about (e.g., ±10%) 4 inches or more, or may be equal to about (e.g., ±10%) 3.4 inches.

[0022] In this embodiment, the separation distance X1 between the magnetic field generating element 14 and the magnetic field generating element 16 is not adjustable. However, in another embodiment, the frame 12 may have an adjustable width, allowing a user to adjust the distance X1 between the magnetic field generating element 14 and the magnetic field generating element 16 and then lock the magnetic field generating element 14 and the magnetic field generating element 16 in position.

[0023] 1-4, the frame 12 may be constructed by a first vertical sidewall 30, a second vertical sidewall 32, and a horizontal bottom wall 34. The first vertical sidewall 30 and the second vertical sidewall 32 may be arranged parallel to each other as shown in the figures, or in another embodiment, may be arranged at a non-parallel angle to each other. The horizontal bottom wall 34 may extend between the first vertical sidewall 30 and the second vertical sidewall 32 and may provide the necessary structural support to prevent the first vertical sidewall 30 and the second vertical sidewall 32 from moving relative to each other due to the existence of magnetic attractive and / or repulsive forces between the magnetic field generating elements 14, 16, and the magnetic beads 40 disposed within the vessel 20. Additional structural support may be provided by one or more beams 34a-d extending between the first vertical sidewall 30 and the second vertical sidewall 32 as shown in FIGS. 1-3. In another embodiment, the bottom wall 34 may be omitted and only one or more beams 34a-d may be included to keep the first vertical sidewall 30 and the second vertical sidewall 32 separated. In yet another embodiment, the beams 34a-d may be omitted and only the bottom wall 34 may be included to maintain the separation distance between the first vertical sidewall 30 and the second vertical sidewall 32.

[0024] As shown in FIGS. 1-3, the frame 12 does not include a front wall, a top wall, or a back wall. Instead of a front wall, an opening 18 (i.e., a front opening) is defined between a first vertical side wall 30 and a second vertical side wall 32. Similarly, instead of a top wall and a back wall, a top opening 26 and a back opening 28 are defined between the first vertical side wall 30 and the second vertical side wall 32, respectively. In another embodiment, a top wall and / or a back wall may be included such that the only openings are the front opening 18 and the back opening 28, or only the front opening 18 and the top opening 26, or only the front opening 18. In yet another embodiment, the top opening 26 may be the only opening formed in the frame 12. In the illustrated embodiment, the front opening 18 is separated from the top opening 26 by a beam 34a, and the top opening 26 is separated from the back opening 28 by a beam 34b. In other embodiments in which beams 34a and 34b are omitted, front opening 18, top opening 26 and rear opening 28 may be continuous with one another (see, for example, FIG. 5).

[0025] Additionally, although the vertical side walls 30 and 32 and the horizontal bottom wall 34 are shown as solid structures extending continuously along the entire length of the separator 10, in alternative embodiments, to reduce the weight of the frame 12, one or more of the vertical walls 30 and 32 and / or the horizontal bottom wall 34 may be formed by one or more struts or girders having gaps therebetween or may have one or more cutouts.

[0026] Frame 12 may be constructed from rigid materials, including but not limited to certain types of metals and / or plastics. The rigidity of frame 12 should be such that the magnetic attractive and / or repulsive forces existing between magnetic field generating elements 14 and 16 and magnetic beads 40 disposed within container 20 do not cause frame 12 to deform. In some embodiments, frame 12 may be constructed from non-magnetic materials, such as, for example, plastic and / or aluminum, while in other embodiments, frame 12 may be made of a magnetic material, such as ferritic stainless steel.

[0027] 1-4, the first magnetic field generating element 14 may be rigidly secured to the inwardly facing surface 36 of the first vertical sidewall 30, and the second magnetic field generating element 16 may be rigidly secured to the inwardly facing surface 38 of the second vertical sidewall 32. In some embodiments, the first magnetic field generating element 14 and / or the second magnetic field generating element 16 may be rigidly secured with fasteners, such as, for example, bolts and / or screws. Furthermore, in some embodiments, each of the first magnetic field generating element 14 and / or the second magnetic field generating element 16 may be housed within a corresponding cage or other enclosure 44 or enclosure 46 rigidly secured to the inwardly facing surface 36 of the first vertical sidewall 30 or the inwardly facing surface 38 of the second vertical sidewall 32. Each of the cages 44 and 46 may have a side opening 48 or a side opening 50 that allows the first magnetic field generating element 14 or the second magnetic field generating element 16 to be slidably inserted into or removed from its corresponding cage 44 or cage 46.

[0028] Each of the magnetic field generating elements 14 and 16 may be mounted such that its downwardly facing or bottom surface is vertically spaced a distance X2 from the horizontal bottom wall 34, or from the surface on which the frame 12 rests if the horizontal bottom wall 34 is omitted. As described below, this may provide space or clearance for inserting the sides of a non-magnetic support shelf under the first magnetic field generating element 14 and the second magnetic field generating element 16, respectively.

[0029] 4, the first magnetic field generating element 14 and the second magnetic field generating element 16 protrude inwardly from the inward facing surface 36 of the first vertical sidewall 30 and the inward facing surface 38 of the second vertical sidewall 32, respectively. In another embodiment, the first magnetic field generating element 14 and the second magnetic field generating element 16 may be disposed in corresponding recesses or depressions formed in the inward facing surface 36 of the first vertical sidewall 30 and the inward facing surface 38 of the second vertical sidewall 32, respectively. Thus, the first magnetic field generating element 14 and the second magnetic field generating element 16 may be flush with the inward facing surface 36 and the inward facing surface 38, respectively.

[0030] In some embodiments, the first magnetic field generating element 14 and the second magnetic field generating element 16 may have a generally flat or planar shape with a rectangular cross-section as shown in FIG. 4. However, other shapes and cross-sections are possible. Also, magnetic field generating elements other than those shown in the figures may be included. Furthermore, in some embodiments, only a single magnetic field generating element may be included, such that one of the vertical sidewalls 30 or 32 does not have a magnetic field generating element.

[0031] In some embodiments, each of the magnetic field generating elements 14 and 16 may be constructed from a corresponding permanent magnet configured to generate its own permanent magnetic field. Each of the permanent magnets may have a maximum magnetic attraction force in the range of about (e.g., ±10%) 50-1000 Newtons (N), or about (e.g., ±10%) 100-800 N, or about (e.g., ±10%) 100-700 N, or about (e.g., ±10%) 150-600 N, or about (e.g., ±10%) 200-500 N, or about (e.g., ±10%) 200-450 N, or about (e.g., ±10%) 50 N or more, or about (e.g., ±10%) 100 N or more, or about (e.g., ±10%) 150 N or more, or about (e.g., ±10%) 200 N or more, or about (e.g., ±10%) 250 N or more. In some embodiments, the combined total magnetic attractive force of the permanent magnets may be about (e.g., ±10%) 500 N or more, or about (e.g., ±10%) 1000 N or more, or about (e.g., ±10%) 1500 N or more, or about (e.g., ±10%) 2000 N or more, or about (e.g., ±10%) 2500 N or more. In some embodiments, the permanent magnets that make up the magnetic field generating element 14 and the magnetic field generating element 16 may be nickel-plated neodymium block magnets. In another embodiment, each of the magnetic field generating element 14 and the magnetic field generating element 16 may be comprised of a respective electromagnet configured to generate a magnetic field when supplied with an electric current.

[0032] 4, the magnetic separator 10 may include a non-magnetic support shelf 50 that is separate from and movable relative to the frame 12. Generally, the non-magnetic support shelf 50 may be configured to hold a number of vessels 20 containing a medium 54 in which the target material T is initially suspended. In some embodiments, the non-magnetic support shelf 50 may be configured to prevent lateral movement of the vessels 20 relative to one another due to magnetic attraction and / or repulsion forces that exist between the magnetic field generating elements 14 and 16 and the magnetic beads 40 disposed within the vessels 20. This aspect of the non-magnetic support shelf 50 may be accomplished by a variety of structures including, for example, forming the non-magnetic support shelf 50 with a number of wells each dimensioned to receive one of the vessels 20, or by rigidly fastening the vessels 20 to the non-magnetic support shelf 50 by one or more fasteners or adhesives, or by integrally joining the vessels 120 by the support shelf 150 such that the vessels 120 form a single, integral structure, as shown in the embodiment depicted in FIG. 5. The non-magnetic support shelf 50 may be constructed of any non-magnetic material, including, for example, plastic or glass, so as not to be magnetically attracted or repelled by the first and second magnetic field generating elements 14, 16. The container 20 may also be constructed of a non-magnetic material, including, for example, glass or plastic.

[0033] In some embodiments, the non-magnetic support shelf 50 may be configured to hold one, two, three, or more rows of containers 20. Further, in some embodiments, each row of containers 20 formed by the non-magnetic support shelf 50 may extend longitudinally in a direction parallel to the first vertical sidewall 30 and the second vertical sidewall 32.

[0034] The non-magnetic support shelf 50 may have a width or may be dimensioned such that it can be inserted generally horizontally through the front opening 18 of the frame 12. This insertion may result in the container 20 being disposed in the space between the first magnetic field generating element 14 and the second magnetic field generating element 16. In some embodiments, such as shown in FIG. 4, the width W1 of the non-magnetic support shelf 50 may be greater than the distance X1 separating the first magnetic field generating element 14 and the second magnetic field generating element 16. In such embodiments, the height H1 of the non-magnetic support shelf 50 may be less than the vertical distance X2 separating the bottom surface of the first magnetic field generating element 14 and the bottom surface of the second magnetic field generating element 16 from the horizontal bottom wall 34 of the frame 12. Thus, the first lateral end 56 and the second lateral end 58 of the non-magnetic support shelf 50 may fit beneath the first magnetic field generating element 14 and the second magnetic field generating element 16, respectively. This configuration may advantageously limit lateral movement of the non-magnetic support shelf 50 due to inertia of the magnetic beads 40 being magnetically attracted by the magnetic field generating elements 14 and 16 to the corresponding interior surfaces of the container 20 because the first lateral end 56 and the second lateral end 58 of the non-magnetic support shelf 50 may abut the inwardly facing surfaces 36 and 38 of the first vertical side walls 30 and 32, respectively, thereby preventing significant lateral movement of the non-magnetic support shelf 50.

[0035] Referring to Figure 5, another embodiment of a magnetic separator 110 according to the principles of the present disclosure is shown. Magnetic separator 110 is similar to magnetic separator 10 except that magnetic separator 110 does not include a beam extending between vertical walls 130 and 132 of frame 112. Elements of magnetic separator 110 shown in Figure 5 that are the same as or similar to elements of magnetic separator 10 shown in Figures 1-4 are designated by the same reference numerals increased by 100. A description of these similar components is omitted for the sake of brevity.

[0036] The lack of a beam extending between the vertical walls 130 and 132 of the frame 112 allows the front opening 118, the top opening 126 and the rear opening 128 to be continuous with one another. Thus, the space between the first magnetic field generating element 114 and the second magnetic field generating element 116 can be made more accessible to a user, and there can be more than one insertion path for the non-magnetic support shelf 150.

[0037] Referring now to Figures 6A-6G, a method of using magnetic separator 10 in a purification process will be described. Figures 6A-6G are schematic side views and omit various elements of magnetic separator 10. The omission of these elements should not be understood to mean that they are necessarily absent from magnetic separator 10. Additionally, magnetic separator 110 may be used in processes similar to those described in Figures 6A-6G.

[0038] As a first step, each or any of the containers 20 may be filled with a volume of medium 54 containing the target substance T. Next, as shown in FIG. 6A, the magnetic beads 40 may be added to the containers 20 and left to interact with the medium 54 for a period of time (e.g., minutes, an hour, several hours, a day, days, etc.). During this incubation period, the magnetic beads 40 may bind to the target substance T, thereby isolating the target substance T from the remainder of the medium 54 (see FIG. 6B). As mentioned above, the binding between the magnetic beads 40 and the target substance T may be achieved covalently, non-covalently, electrostatically, by hydrogen bonding, by van der Waals forces, and / or by any other suitable molecular binding process. In some embodiments, the medium 54 may be agitated or stirred during the incubation period to promote binding between the target substance T and the magnetic beads 40. Furthermore, in some embodiments, the containers 20 may be placed in a magnetic separator 10 during the period during which the magnetic beads 40 bind to the target substance T.

[0039] Next, if not already done, the container 20 may be secured to the non-magnetic support shelf 50, and the non-magnetic support shelf 50 may be inserted into the frame 12 between the first vertical sidewall 30 and the second vertical sidewall 32 such that the container 20 is disposed between the first magnetic field generating element 14 and the second magnetic field generating element 16, as shown in FIG. 6C. This step may require a user to manually move the non-magnetic support shelf 50, with the container 20 disposed on the non-magnetic support shelf 50, from a first position located outside the frame 12 to a second position located within the frame 12, between the first vertical sidewall 30 and the second vertical sidewall 32. In some embodiments, this action may include inserting the non-magnetic support shelf 50 and the container 20 horizontally through the front opening 18 of the frame 12. In some embodiments, the first and second lateral ends 56, 58 of the non-magnetic support shelf 50 may slide or fit underneath the first and second magnetic field generating elements 14, 16 during insertion. In other embodiments, the non-magnetic support shelf 50 and container 20 may be inserted vertically downward through the top opening 26 or horizontally through the rear opening 28.

[0040] 6C, when the container 20 is disposed between the first vertical sidewall 30 and the second vertical sidewall 32, the proximity of the first magnetic field generating element 14 and the second magnetic field generating element 16 can enable them to magnetically attract and hold the magnetic beads 40 against the corresponding inner surface 60 of the sidewall 61 of the container 20. Friction between the magnetic beads 40 and the inner surface 60 of the container 20 can effectively immobilize or secure the magnetic beads 40 to the container 20 so as to inhibit or prevent the magnetic beads 40 from moving during subsequent fluid removal and addition steps.

[0041] Next, as shown in FIG. 6D, the purification method may include aspirating or removing the medium 54 from the container 20 through a fluid transfer member 62, such as, for example, a pipette or other fluid conduit. The tip or mouth of the fluid transfer member 62 may be inserted through the top opening of the frame 12 and then into an opening 64 formed in the top of one of the containers 20 so that it is submerged in the medium 54. The mouth of the fluid transfer member 62 may be located near or very close to the bottom wall 66 of the container 20 so that the fluid transfer member 62 can aspirate all or substantially all of the medium 54 in the container 20. The magnetic beads 40 are not removed in this step because they are held against the inner surface 60 of the side wall 61 of the container 20 by the magnetic attraction of the first magnetic field generating element 14 and / or the second magnetic field generating element 16. Furthermore, the target substance T bound to the magnetic beads 40 is also left in the container 20. This process of removing the medium 54 from which the target substance T has been removed may be repeated for all of the containers 20, or in some embodiments, may be performed simultaneously for all of the containers 20 using multiple fluid transfer members.

[0042] After removal of the medium 54, a washing fluid 70 (e.g., a salt solution) may be added to the container 20 through a fluid transfer member 62 or another fluid conduit, as shown in FIG. 6E, to clean the inner surface 60 of the container 20 and / or the magnetic beads 40 of the residual medium 54. However, the washing fluid 70 may not remove the target substance T from the magnetic beads 40. The volume of the washing fluid 70 added to the container 20 may be less than (e.g., a fraction of) the maximum volume of the corresponding container 20. Optionally, immediately before or after adding the washing fluid 70 to the container 20, the container 20 or the entire shelf of the container 20 may be removed from the frame 12 so that the container 20 is not positioned between the first magnetic field generating element 14 and the second magnetic field generating element 16. Due to the lack of the relatively strong magnetic fields of the magnetic field generating element 14 and the magnetic field generating element 16, the magnetic beads 40 can be freely dispersed in the washing fluid 60 and can be suspended in the washing fluid 60. Allowing the magnetic beads 40 to disperse in this manner may enhance the effectiveness of the washing process and / or allow for stirring or other agitation of the magnetic beads 40 in the washing fluid 70. After washing is completed, the washing fluid 70 may be removed from the container 20 through the fluid transfer member 62 or other fluid conduit.

[0043] In another embodiment, one or more or all of the steps relating to the cleaning fluids described above may be omitted.

[0044] Next, as shown in FIG. 6F, an eluant 72 (e.g., a liquid elution solution) may be added to the container 20 through the fluid transfer member 62 or another fluid conduit to release the target material T from the magnetic beads 40. If not already done, immediately before or after adding the eluant 72 to the container 20, the container 20 or the entire shelf of the container 20 may be removed from the frame 12 so that the container 20 is not located between the first magnetic field generating element 14 and the second magnetic field generating element 16. Due to the lack of the relatively strong magnetic fields of the magnetic field generating element 14 and the magnetic field generating element 16, the magnetic beads 40 may be freely dispersed in the eluant 72 and may be suspended in the eluant 72. Allowing the magnetic beads 40 to disperse in this manner may enhance the effectiveness of the elution process and / or allow stirring or other agitation of the magnetic beads 40 in the eluant 72. Optionally, this elution step may be performed while the container 20 is located between the first magnetic field generating element 14 and the second magnetic field generating element 16.

[0045] After the incubation period, the eluant 72 and the target substances T bound to the eluant 72 may be removed from the containers 20 through the fluid transfer member 62 or another conduit and then discharged into an external container. If not already done, just prior to this fluid removal step, the containers 20 may be repositioned between the first and second magnetic field generating elements 14, 16 such that the magnetic beads 40 are immobilized against the interior surfaces 60 of their corresponding containers 20. The above steps may then be repeated for another container or batch of containers containing another medium or mixture requiring purification.

[0046] It should be noted that any of the previously described steps of placing the container 20 between the first and second magnetic field generating elements 14, 16 and / or removing the container 20 from between the first and second magnetic field generating elements 14, 16 may be performed manually by a user, such as a laboratory technician. A user may also perform any of the fluid addition or removal steps manually, for example, with the aid of a pipette. It should further be noted that the magnetic separator 10 may be sized or constructed such that it can be supported on a variety of standard laboratory benches and / or tabletops.

[0047] 7 and 8, a schematic diagram of a workstation 200 for separating target substances from a medium in which they are suspended, according to the principles of the present disclosure, is shown. The workstation 200 is similar in some respects to the magnetic separator embodiments described above, since it uses one or more magnetic field generating elements to immobilize magnetic beads submerged in the medium and bound to the target substances during fluid removal steps, such as, for example, medium removal, washing fluid removal, and / or elution fluid removal. However, the workstation 200 differs from the magnetic separator embodiments described above in that the vessel remains stationary while one or more magnetic field generating elements move between various positions during the purification process. Furthermore, unlike the magnetic separators described above, the workstation 200 incorporates an automated manipulator configured to move at least one fluid transfer member relative to the vessel for fluid removal and / or addition purposes.

[0048] In general, the workstation 200 may be sized or constructed to be supported on a variety of standard laboratory workbenches and / or tabletops. With reference to FIGS. 7-9, the workstation 200 may generally include a frame 210 including a horizontally disposed and upwardly facing work surface 212, a fluid transfer member 214, an automated manipulator 216, and one or more magnetic field generating elements 218a-e. Optionally, the workstation 200 may include one or more linear actuators 220a-e connected to the one or more magnetic field generating elements 218a-e, one or more pumps 222a-b in fluid communication with the fluid transfer member 214, a multi-position valve 224 in fluid communication with the one or more pumps 222a-b, a waste container or drain 226, one or more auxiliary containers 228a-c containing one or more eluents, wash fluids, and / or other fluids, and / or a control unit 230.

[0049] 7, the magnetic field generating elements 218a-e may be horizontally spaced laterally from one another at regular intervals to define a plurality of rows 232a-d for slidably receiving a plurality of containers 240. In some embodiments, the lateral distance X3 separating adjacent ones of the magnetic field generating elements 218a-e may be within a range of about (e.g., ±10%) 3-10 inches, or within a range of about (e.g., ±10%) 3-8 inches, or within a range of about (e.g., ±10%) 3-6 inches, or within a range of about (e.g., ±10%) 3-5 inches, or about (e.g., ±10%) 1 inch or more, or about (e.g., ±10%) 2 inches or more, or about (e.g., ±10%) 3 inches or more, or about (e.g., ±10%) 4 inches or more, or may be equal to about (e.g., ±10%) 3.4 inches.

[0050] Each of the containers 240 may first be filled with a medium 242 having a target material T suspended therein. Each of the containers 240 may have an opening 244 formed in its top, an interior surface 246, a sidewall 248, and a bottom wall 250 connected to the sidewall 248. The medium 242 and target material T may be similar to those described above. Within each row 232a-d, the containers 240 may be held by a non-magnetic support shelf 252, which in some embodiments may be configured in a manner similar to the non-magnetic support shelf described above.

[0051] A plurality of magnetic beads 260 may be submerged in the medium 242 within each vessel 240. The magnetic beads 260 may be constructed in a manner similar to the beads 40 described above and may be configured to bind to a target substance T suspended in the medium 242.

[0052] Each magnetic field generating element 218a-e may extend longitudinally along a longitudinal axis A (see FIG. 8). Furthermore, in some embodiments, the longitudinal axes A of the magnetic field generating elements 218a-e may be parallel to one another. The length L2 of each magnetic field generating element 218a-e may be parallel to the longitudinal axis A of the corresponding magnetic field generating element, and the width W2 of the magnetic field generating element 218a-e may be perpendicular to the longitudinal axis A of the corresponding magnetic field generating element. In some embodiments, the length L2 may be within a range of about (e.g., ±10%) 10 to 48 inches, or within a range of about (e.g., ±10%) 10 to 36 inches, or within a range of about (e.g., ±10%) 10 to 30 inches, or within a range of about (e.g., ±10%) 10 to 24 inches, or about (e.g., ±10%) 10 inches or more, or about (e.g., ±10%) 20 inches or more, or about (e.g., ±10%) 30 inches or more. In some embodiments, the width W2 may be within a range of about (e.g., ±10%) 0.5 to 6 inches, or within a range of about (e.g., ±10%) 0.5 to 4 inches, or within a range of about (e.g., ±10%) 0.5 to 3 inches, or within a range of about (e.g., ±10%) 0.5 to 2 inches, or about (e.g., ±10%) 0.5 inches or more, or about (e.g., ±10%) 1 inch or more, or about (e.g., ±10%) 1.5 inches or more, or about (e.g., ±10%) 2 inches or more, or about (e.g., ±10%) 2.5 inches or more.

[0053] Each magnetic field generating element 218a-e may be movable back and forth relative to the work surface 212 between a first or non-operating position away from its corresponding row of containers 240 and a second or operating position adjacent (e.g., directly adjacent) to its corresponding row of containers 240. FIG. 8 shows one of the magnetic field generating elements 218a-e in its operating position in a schematic solid line. FIG. 8 also shows the non-operating position of one of the magnetic field generating elements 218a-e in a dashed line. In this embodiment, the workstation 200 includes multiple linear actuators 220a-e, each configured to independently reciprocate a corresponding one of the magnetic field generating elements 218a-e in a linear horizontal direction between its operating and non-operating positions. In other embodiments, a single linear actuator may be used to simultaneously reciprocate all of the magnetic field generating elements 218a-e together between their operating and non-operating positions. Each linear actuator 220a-e may include at least one of a hydraulic cylinder, a pneumatic cylinder, or an electric motor. In embodiments including a hydraulic or pneumatic cylinder, a reciprocating piston may connect the hydraulic or pneumatic cylinder to a corresponding one of the magnetic field generating elements 218a-e. In embodiments including a rotary electric motor, a rack and pinion mechanism, pulleys, or gear system may be used to convert the rotary motion output generated by the electric motor into linear motion of a corresponding one of the magnetic field generating elements 218a-e.

[0054] In the embodiment shown in FIG. 8, each linear actuator 220a-e takes the form of a pneumatic linear slide. Each linear actuator 220a-e may therefore include a pneumatic cylinder 221a-e for receiving pressurized gas and a piston or carrier element 223a-e for reciprocating translation by pressurizing different ends of the pneumatic cylinder 221a-e. As shown in FIG. 8, each pneumatic cylinder 221a-e may be disposed vertically below the working surface 212 within the interior space of the frame 210. Each carrier element 223a-e may be mechanically connected to a corresponding one of the magnetic field generating elements 218a-e through a corresponding opening 225a-e formed in the working surface 212. Although FIG. 8 only shows the linear actuator 220e and its connection to the magnetic field generating element 218e, the other magnetic field elements 218a-d and linear actuators 220a-d may be constructed in a similar manner and are not shown for the sake of simplicity. In another embodiment, the linear actuator 220e may be configured to move all of the magnetic field generating elements 218a-e together.

[0055] Although the magnetic field generating elements 218a-e in this embodiment are movable in a horizontal direction parallel to the work surface 212, in other embodiments, each magnetic field generating element 218a-e may be movable in a vertical direction perpendicular or non-parallel to the work surface 212. In such other embodiments, a plurality of openings may be formed in the work surface 212, and each magnetic field generating element 218a-e may be configured to reciprocally retract into and extend from a corresponding one of the openings, where the retracted position (which may be below the work surface 212) may correspond to a non-operating position, and the extended position (which may be above the work surface 212) may correspond to an operating position.

[0056] 9, the linear actuators 220a-e may be omitted. In such embodiments, movement of the magnetic field generating elements 218a-e may be accomplished by a user manually moving each magnetic field generating element 218a-e horizontally and / or vertically between its operative and non-operative positions.

[0057] When the magnetic field generating elements 218a-e occupy their corresponding operating positions, they can magnetically attract and hold the magnetic beads 260 against the inner surfaces 246 of the side walls 248 of the containers 240. Friction between the magnetic beads 260 and the inner surfaces 246 of the containers 240 can effectively immobilize or secure the magnetic beads 260 to their corresponding ones of the containers 240 so as to inhibit or prevent the magnetic beads 260 from moving during subsequent fluid removal and / or addition steps.

[0058] In some embodiments, each magnetic field generating element 218a-e may be constructed from a corresponding permanent magnet configured to generate its own permanent magnetic field. Each of the permanent magnets may have a maximum magnetic attractive force within the range of about (e.g., ±10%) 50 to 1000 Newtons (N), or within the range of about (e.g., ±10%) 100 to 800 N, or within the range of about (e.g., ±10%) 100 to 700 N, or within the range of about (e.g., ±10%) 150 to 600 N, or within the range of about (e.g., ±10%) 200 to 500 N, or within the range of about (e.g., ±10%) 200 to 450 N, or within the range of about (e.g., ±10%) 250 to 350 N, or about (e.g., ±10%) 50 N or more, or about (e.g., ±10%) 100 N or more, or about (e.g., ±10%) 150 N or more, or about (e.g., ±10%) 200 N or more, or about (e.g., ±10%) 250 N or more, or equal to about (e.g., ±10%) 289 N. In some embodiments, the total magnetic attractive force of the permanent magnets may be about (e.g., ±10%) 500 N or more, or about (e.g., ±10%) 1000 N or more, or about (e.g., ±10%) 1500 N or more, or about (e.g., ±10%) 2000 N or more, or about (e.g., ±10%) 2500 N or more, or about (e.g., ±10%) 5000 N or more, or about (e.g., ±10%) 7000 N or more, or about (e.g., ±10%) 7500 N or more, or may be equal to about (e.g., ±10%) 7225 N. In some embodiments, the permanent magnets constituting the magnetic field generating elements 218a-e may be nickel-plated neodymium block magnets. In another embodiment, each magnetic field generating element 218a-e may be composed of a respective electromagnet configured to generate a magnetic field when supplied with an electric current.

[0059] 7-9, the automated manipulator 216 may be configured to automatically move the fluid transfer member 214 relative to the work surface 212 to various positions that may or may not be predefined or preprogrammed. The automated manipulator 216 may include one or more electric motors controlled by the control unit 230. In the illustrated embodiment, the automated manipulator 216 takes the form of a Cartesian coordinate robot that is independently movable in each of the x, y, and z directions. In this embodiment, the x and y directions are horizontal linear directions, and the z direction is a vertical linear direction. The automated manipulator 216 may include separate electric motors and separate track members to achieve each direction of movement. In other embodiments, the automated manipulator 216 may allow movement in only two directions (e.g., only x and y directions, or only x and z directions, or only y and z directions), or only one linear direction. In yet another embodiment, the automated manipulator 216 may take the form of a robotic arm capable of complex curvilinear, linear and / or rotational motion.

[0060] 7-9, the automated manipulator 216 may include a mounting plate 262 for mounting the fluid transfer member 214, the pumps 222a-b, the multi-position valve 224, and / or other components carried by the automated manipulator 216. The fluid transfer member 214 may be mechanically connected (e.g., fastened by fasteners) to the mounting plate 262 and may extend vertically downward from the mounting plate 262. In this embodiment, the fluid transfer member 214 includes two parallel vertical fluid conduits 264a and 264b (e.g., flexible or rigid plastic tubes) spaced apart from each other a horizontal distance. The fluid conduit 264a may be in fluid communication with the pump 222a, and the fluid conduit 264b may be in fluid communication with the pump 222b. The horizontal distance separating the two fluid conduits 264a and 264b may be equal to the horizontal distance separating the centers of any two adjacent rows of the rows 232a-d. Additionally, in some embodiments, the horizontal distance separating the two fluid conduits 264a and 264b may be adjustable to accommodate different sized vessels 240. In other embodiments, the fluid transfer member 214 may include only one vertical fluid conduit or three or more vertical fluid conduits.

[0061] Generally, each pump 222a-b may be configured to remove and / or add fluid to a corresponding one of the vessels 240 through the fluid transfer member 214. Each pump 222a-b may be powered by any suitable means, including, but not limited to, an electric motor and / or a source of pressurized hydraulic fluid and / or gas. Each pump 222a-b may be operated at variable speed or at a single speed depending on the specifications of the purification process. In some embodiments, the operation of one or more of the pumps 222a-b may be electronically controlled by the control unit 230, for example, according to programmable instructions stored in a memory of the control unit 230. Alternatively or additionally, each pump 222a-b may be operated by a user (e.g., a lab technician) manually activating an on / off switch and / or turning a speed knob. In some embodiments, such as the embodiment shown in Figure 9, one or more of the pumps 222a-b may be configured as a positive displacement pump, such as a peristaltic pump, and may be capable of pumping fluids containing suspended solids (e.g., magnetic beads 260) without damaging the solids. In another embodiment, one or more of the pumps 222a-b may be a centrifugal pump, such as a radial flow pump that uses a rotating impeller to create a vacuum to move the fluid. Additionally, in some embodiments, each pump 222a-b may be reversible.

[0062] Multi-position valve 224 may be configured to selectively fluidly connect pump 222a and / or pump 222b to one or more of auxiliary vessels 228a-c, drain 226, and / or other elements. Depending on the number of auxiliary vessels, drains, etc., multi-position valve 224 may be a 3-way valve, 4-way valve, 5-way valve, 6-way valve, 7-way valve, 8-way valve, or any other valve having any number of selectively openable orifices. In some embodiments, operation of multi-position valve 224 may be electronically controlled by control unit 230, for example, according to programmable instructions stored in a memory of control unit 230. Multi-position valve 224 may incorporate one or more solenoids for opening and closing orifices of multi-position valve 224 in response to command signals from control unit 230.

[0063] Generally, the control unit 230 may be electrically connected to at least the automated manipulator 216, the pumps 222a-b, and the linear actuators 220a-e (if included) such that the control unit 230 may send and / or receive electrical control signals to and from these components. The control unit 230 may include a processor (e.g., a microprocessor), memory for storing tangible, non-transitory computer-readable instructions (e.g., random access memory (RAM), non-volatile memory such as a hard disk executable by the processor, flash memory, removable memory, non-removable memory, etc.), a communication unit, a display, and input devices (e.g., keyboard, keypad, touch screen, etc.). In some embodiments, the control unit 230 may be a programmable logic controller. The control unit 230 may be programmed to execute the purification process according to a user's predefined specifications. In some embodiments, the control unit 230 may be included in or used in conjunction with the workstation 200 to perform steps of the purification process, such as actuating the automated manipulator 216 to move the fluid transfer member 214 and / or actuating one or more of the linear actuators 220a-e to move one or more of the magnetic field generating elements 218a-e, in response to sensor data received from one or more sensors representing characteristics of the medium 242 and / or the target substance T (e.g., volume, temperature, weight, pH, etc.), a timer, an operator analog or digital input, and / or any other relevant detectable event or occurrence.

[0064] We now describe how the workstation 200 can be used in a purification process. As a first step, each or any of the containers 240 can be filled with a volume of the medium 242 containing the target substance T. Then, the magnetic beads 260 can be added to the containers 240 and left to interact with the medium 242 for a period of time (e.g., minutes, an hour, several hours, a day, days, etc.). During this incubation period, the magnetic beads 260 can bind to the target substance T, thereby isolating the target substance T from the remainder of the medium 242 (similar to FIG. 6B). As mentioned above, the binding between the magnetic beads 260 and the target substance T can be achieved covalently, non-covalently, electrostatically, by hydrogen bonding, by van der Waals forces, and / or by any other suitable molecular binding process. In some embodiments, the medium 242 can be agitated or stirred during the incubation period to promote binding between the target substance T and the magnetic beads 242.

[0065] Next, if not already done, the containers 240 may be paired and secured to the plurality of non-magnetic support shelves 252. Each filled non-magnetic support shelf 252 may then be inserted horizontally between a corresponding pair of magnetic field generating elements 218a-e on the work surface 212, thereby placing each container 240 in one of the rows 232a-d defined between adjacent ones of the magnetic field generating elements 218a-e. This step may include a user manually placing each non-magnetic support shelf 252 in a corresponding one of the rows 232a-d. This insertion step may be performed with each magnetic field generating element 218a-e positioned in their corresponding operating position (see FIG. 9) or with each magnetic field generating element 218a-e positioned in their corresponding operating position. In the latter case, the magnetic field generating elements 218a-e may be moved to their corresponding operating position after the non-magnetic support shelf 252 is positioned on the work surface 212.

[0066] The proximity of the magnetic field generating elements 218a-e may enable them to magnetically attract and hold the magnetic beads 260 against the interior surfaces 246 of the sidewalls 248 of their corresponding containers 240. Friction between the magnetic beads 260 and the interior surfaces 246 of the containers 240 may effectively immobilize or secure the magnetic beads 260 to the containers 240 so as to inhibit or prevent the magnetic beads 260 from moving during subsequent steps of removing and adding fluids to the containers 240.

[0067] The purification method may then include aspirating or removing the medium 242 from the vessel 240 through the fluid transfer member 214. To do this, the control unit 230 may control the automanipulator 216 to move the fluid transfer member 214 horizontally, for example, in the x and / or y directions, until the fluid conduit 264a is positioned vertically directly above and the fluid conduit 264b is positioned vertically directly above a second vessel of the vessel 240. The control unit 230 may then control the automanipulator 216 to move the fluid transfer member 214 vertically downward (i.e., along the z-axis) such that the first fluid conduit 264a is inserted through an opening 244 at the top of a first vessel of the vessel 240 and is submerged in the medium 242 therein, and the second fluid conduit 264b is inserted through an opening 244 at the top of a second vessel of the vessel 240 and is submerged in the medium 242 contained therein. The fluid transfer member 214 may be moved vertically downward by the automated manipulator 216 until the mouth of the first fluid conduit 264a is adjacent or very close to the bottom wall 250 of the first vessel of the vessel 240 and the second fluid conduit 264b is adjacent or very close to the bottom wall 250 of the second vessel of the vessel 240. So configured, the first fluid conduit 264a and the second fluid conduit 264b may be able to aspirate all or substantially all of the medium 242 from their corresponding vessels 240. The pumps 222a and 222b may be activated by the control unit 230 to generate the suction force necessary to remove the medium 242 from the vessel 240 after the fluid transfer member 214 is properly positioned. The magnetic beads 260 are not removed in this process because they are statically held against the inner surface 246 of the sidewall 248 of the vessel 240 by the magnetic attraction of the magnetic field generating elements 218a-e. Also, during this aspirating process, multi-position valve 224 may be controlled to fluidly connect each pump 222a and pump 222b to a waste container or drain 226 so that the aspirated fluid is discharged to the waste container or drain 226.

[0068] Once suction is complete, the control unit 230 may control the automated manipulator 216 to move the fluid transfer member 214 vertically upward to remove the first fluid conduit 264a and the second fluid conduit 264b from their corresponding containers 240, and then repeat the process in the previous paragraph for other containers 240 positioned on the work surface 212.

[0069] Next, a washing fluid (e.g., a salt solution) may be added to the container 240 through the fluid transfer member 214 to clean the inner surface 246 of the container 240 and / or the magnetic beads 260 of the residual medium 242 without removing the target substance T from the magnetic beads 260. First, similar to the medium removal step described above, the control unit 230 may control the automanipulator 216 to move the fluid transfer member 214 horizontally such that the fluid conduit 264a is positioned vertically directly above a first container of the container 240 and the fluid conduit 264b is positioned vertically directly above a second container of the container 240. The control unit 230 may then control the automanipulator 216 to move the fluid transfer member 214 vertically downward (i.e., along the z-axis) such that the first fluid conduit 264a is inserted through the opening 244 in the top of the first vessel of the vessel 240 and the second fluid conduit 264b is inserted through the opening 244 in the top of the second vessel of the vessel 240. At or near the same time, the control unit 230 may control the multi-position valve 224 to fluidly connect each of the pumps 222a and 222b with one or more of the auxiliary vessels 228a-c that contain the cleaning fluid. The control unit 230 may then operate the pumps 222a and 222b to draw the cleaning fluid from one or more of the auxiliary vessels 228a-c and transfer the cleaning fluid through the fluid transfer member 214 to the vessel 240.

[0070] Once the cleaning fluid has been added to the first and second ones of the containers 240, the control unit 230 may control the automated manipulator 216 to move the fluid transfer member 214 vertically upward to remove the first and second fluid conduits 264a and 264b from their corresponding containers 240, and then repeat the process in the previous paragraph for other containers 240 positioned on the work surface 212.

[0071] Optionally, immediately before or after adding the washing fluid to the vessel 240, the magnetic field generating elements 218a-e may be translated from their corresponding operative positions adjacent the vessel 240 to their corresponding non-operative positions away from the vessel 240. Due to the lack of a relatively strong magnetic field of the magnetic field generating elements 218a-e, the magnetic beads 260 may be freely dispersed in the washing fluid, which may enhance the effectiveness of the washing process and / or allow stirring or other agitation of the magnetic beads 260 in the washing fluid. In some embodiments, the movement of the magnetic field generating elements 218a-e may be achieved by the control unit 230 actuating the linear actuators 220a-e such that each of the linear actuators 220a-e translates a corresponding one of the magnetic field generating elements 218a-e from its corresponding operative position to its corresponding non-operative position.

[0072] After washing is completed, the control unit 230 may control the multi-position valve 224 to fluidly connect the pumps 222a and 222b to the waste containers or drains 226, and may control the automanipulator 216 to move the fluid transfer member 214 between the various containers 240 while controlling the pumps 222a and 222b to draw washing fluid from the containers 240 and expel washing fluid to the drains 226. Prior to this washing fluid removal step, the magnetic field generating elements 218a-e may be translated from their corresponding non-operative positions away from the containers 240 to their corresponding operative positions adjacent the containers 240, if not already done so. As a result, the magnetic fields of the magnetic field generating elements 218a-e may magnetically attract and statically hold the magnetic beads 260 against the inner surfaces 246 of the sidewalls 248 of their corresponding containers 240 while the washing fluid is being removed from the containers 240. The control unit 230 may be responsible for actuating the linear actuators 220a-e to move the magnetic field generating elements 218a-e from their corresponding non-operated positions to their corresponding operative positions.

[0073] In another embodiment, one or more or all of the steps relating to the cleaning fluids described above may be omitted.

[0074] Next, an eluant (e.g., a liquid elution solution) may be added to the vessel 240 through the fluid transfer member 214 to release the target material T from the magnetic beads 260. Here, as a first step, the control unit 230 may control the multi-position valve 224 to fluidly connect the pumps 222a and 222b to one or more of the auxiliary vessels 228a-c that contain the eluant fluid. Also, if not already done, immediately before or after adding the eluant to the vessel 240, the magnetic field generating elements 218a-e may be translated from their corresponding operative positions adjacent the vessel 240 to their corresponding non-operative positions away from the vessel 240. This may be achieved by the control unit 230 actuating the linear actuators 220a-e to move the magnetic field generating elements 218a-e from their corresponding operative positions to their corresponding non-operative positions. The control unit 230 may then control the automanipulator 216 to move the fluid transfer member 214 horizontally such that the fluid conduit 264a is positioned vertically directly above a first one of the vessels 240 and the fluid conduit 264b is positioned vertically directly above a second one of the vessels 240, similar to the cleaning fluid process described above. The control unit 230 may then control the automanipulator 216 to move the fluid transfer member 214 vertically downward (i.e., along the z-axis) such that the first fluid conduit 264a is inserted through the opening 244 in the top of the first vessel of the vessel 240 and the second fluid conduit 264b is inserted through the opening 244 in the top of the second vessel of the vessel 240. The control unit 230 may then operate the pumps 222a and 222b to draw eluent fluid from one or more of the auxiliary containers 228a-c and transfer the eluent fluid through the fluid transfer member 214 to the container 240.

[0075] The lack of a relatively strong magnetic field of the magnetic field generating elements 218a-e allows the magnetic beads 260 to disperse freely in the eluent, which may enhance the effectiveness of the elution process and / or allow stirring or other agitation of the magnetic beads 260 in the eluent. The aforementioned eluent addition process may be repeated for all of the vessels 240. In another embodiment, this elution step may be performed by the magnetic field generating elements 218a-e positioned in their corresponding operating positions.

[0076] After the incubation period, the eluant and target substances T may be removed from the vessel 240 through the fluid transfer member 214 and then discharged to an external vessel. Here, as a first step, the control unit 230 may control the multi-position valve 224 to fluidly connect the pumps 222a and 222b to one or more of the auxiliary vessels 228a-c for storing the eluant fluid mixed with the target substances T. Also, if not already done, the magnetic field generating elements 218a-e may be translated from their corresponding non-operating positions away from the vessel 240 to their corresponding operating positions adjacent the vessel 240. This may be achieved by the control unit 230 actuating the linear actuators 220a-e to move the magnetic field generating elements 218a-e from their corresponding non-operating positions to their corresponding operating positions. As a result, the magnetic fields of the magnetic field generating elements 218a-e may magnetically attract and statically hold the magnetic beads 260 against the inner surfaces 246 of the side walls 248 of their corresponding vessels 240. The control unit 230 may then control the automanipulator 216 to move the fluid transfer member 214 horizontally such that the fluid conduit 264a is positioned vertically directly above the first vessel of the vessels 240 and the fluid conduit 264b is positioned vertically directly above the second vessel of the vessels 240, similar to the washing fluid process described above. The control unit 230 may then control the automanipulator 216 to move the fluid transfer member 214 vertically downward (i.e., along the z-axis) such that the first fluid conduit 264a is inserted through the top opening 244 of the first vessel of the vessels 240 and the second fluid conduit 264b is inserted through the top opening 244 of the second vessel of the vessels 240. The control unit 230 may then operate the pumps 222a and 222b to draw the eluent fluid mixed with the target material T from the vessel 240 and transfer the fluid to one or more of the auxiliary vessels 228a-c. The process of removing the eluent mixed with the target material T may be repeated for all the containers 240 .

[0077] It should be noted that any of the above steps of moving the magnetic field generating elements to and from operative and / or non-operative positions may be performed manually by a user, such as a laboratory technician.

[0078] While the disclosed apparatus, systems, and methods have been described in connection with various embodiments, it will be understood that the disclosed apparatus, systems, and methods are capable of further modifications. This application is intended to cover any variations, uses, or adaptations of the apparatus, systems, and methods generally consistent with the principles of the present disclosure, including such departures from the disclosure as are known and customary within the art to which the invention pertains.

[0079] It should further be noted that the construction and arrangement of the disclosed magnetic separators and workstations and their various components and assemblies as shown in the various exemplary embodiments are merely illustrative. While the present disclosure describes in detail only a few embodiments of the subject matter at issue, one of ordinary skill in the art reviewing the present disclosure will readily appreciate that many modifications (e.g., variations in the size, dimensions, configuration, shape and proportions of the various elements, parameter values, mounting configurations, use of materials, colors, orientations, etc.) are possible without substantially departing from the novel teachings and advantages of the subject matter disclosed herein. For example, elements shown as integrally formed may be composed of multiple parts or elements, and vice versa. Also, the positions of elements may be reversed or otherwise changed, and the nature or number of separate elements or positions may be modified or changed. Accordingly, all such modifications are intended to be included within the scope of the present disclosure as defined in the appended claims. Furthermore, the order or sequence of any process or method steps may be modified or rearranged in accordance with alternative embodiments. Other substitutions, modifications, changes and omissions may be made in the design, operating conditions and arrangements of the various exemplary embodiments without departing from the scope of the present disclosure.

Claims

1. 1. A magnetic separator for separating a target material from a medium in which the target material is suspended, the medium being contained in at least one container, the magnetic separator apparatus comprising: a frame having a first opening configured to receive the at least one container; a first magnetic field generating element and a second magnetic field generating element, the first magnetic field generating element and the second magnetic field generating element being attached to opposite sides of the frame at a distance from each other such that the at least one container can be positioned between the first magnetic field generating element and the second magnetic field generating element; a magnetic separator comprising:

2. 2. The magnetic separator of claim 1, wherein the frame includes a first vertical wall and a second vertical wall, the first magnetic field generating element being mounted on an inwardly facing surface of the first vertical wall and the second magnetic field generating element being mounted on an inwardly facing surface of the second vertical wall.

3. The magnetic separator of claim 2 , wherein the first vertical wall is parallel to the second vertical wall.

4. 4. The magnetic separator of claim 2 or 3, including at least one of a beam or a third wall extending between the inwardly facing surface of the first vertical wall and the inwardly facing surface of the second vertical wall.

5. 5. The magnetic separator of claim 2, wherein the first opening is defined between the first vertical wall and the second vertical wall and allows for the at least one container to be inserted horizontally into the magnetic separator.

6. 6. The magnetic separator of claim 5, including a second opening formed in the frame that allows access to the at least one container from above when the at least one container is disposed between the first magnetic field generating element and the second magnetic field generating element.

7. 7. The magnetic separator of claim 2, further comprising a non-magnetic support shelf configured to hold the at least one container and dimensioned for insertion through the first opening to position the at least one container between the first magnetic field generating element and the second magnetic field generating element.

8. 8. The magnetic separator of claim 7, wherein when inserted through the first opening, a first end of the non-magnetic support shelf fits beneath the first magnetic field generating element and a second end of the non-magnetic support shelf fits beneath the second magnetic field generating element.

9. 9. The magnetic separator of claim 7 or 8, wherein the at least one vessel comprises a plurality of vessels, and the non-magnetic support shelf is configured to prevent lateral movement of the plurality of vessels relative to one another.

10. The magnetic separator of any one of claims 1 to 9, wherein the first magnetic field generating element comprises a first permanent magnet.

11. 11. The magnetic separator of claim 10, wherein the first permanent magnet has a maximum magnetic attraction force of 100 Newtons (N) or greater.

12. 1. A purification method comprising the steps of: adding a medium having a target substance suspended therein to a vessel; adding a plurality of magnetic beads to the vessel, wherein the target substance temporarily binds to the plurality of magnetic beads; disposing the container between a first magnetic field generating element and a second magnetic field generating element, the first magnetic field generating element and the second magnetic field generating element being held at a distance from each other by a frame, and at least one of the first magnetic field generating element or the second magnetic field generating element magnetically attracting and holding the plurality of magnetic beads against an inner surface of the container; A purification method comprising:

13. 13. The purification method of claim 12, wherein placing the container between the first magnetic field generating element and the second magnetic field generating element comprises manually moving the container from a first position outside the frame to a second position located between the first magnetic field generating element and the second magnetic field generating element.

14. The purification method of claim 12 or 13, comprising removing the medium from the vessel while at least one of the first magnetic field generating element or the second magnetic field generating element magnetically attracts and holds the plurality of magnetic beads against the interior surface of the vessel.

15. 15. The purification method of claim 14, comprising, after removing the medium from the vessel, adding an eluent to the vessel to elute the target substance bound to the plurality of magnetic beads, and removing the vessel from between the first magnetic field generating element and the second magnetic field generating element so that the plurality of magnetic beads are freely dispersed in the eluent.

16. 16. The purification method of claim 15, comprising: repositioning the vessel between the first magnetic field generating element and the second magnetic field generating element such that at least one of the first magnetic field generating element or the second magnetic field generating element magnetically attracts and holds the plurality of magnetic beads against the interior surface of the vessel; and then removing the eluent from the vessel.

17. 17. The purification method of any one of claims 14 to 16, comprising adding a washing fluid to the vessel after removing the medium from the vessel, and removing the vessel from between the first magnetic field generating element and the second magnetic field generating element such that the plurality of magnetic beads are freely dispersed in the washing fluid.

18. 18. The purification method of claim 17, comprising: repositioning the container between the first magnetic field generating element and the second magnetic field generating element such that at least one of the first magnetic field generating element or the second magnetic field generating element magnetically attracts and holds the plurality of magnetic beads against the interior surface of the container; and then removing the washing fluid from the container.

19. The purification method of any one of claims 12 to 18, wherein the frame includes a first vertical wall and a second vertical wall, the first magnetic field generating element being mounted on an inward facing surface of the first vertical wall, and the second magnetic field generating element being mounted on an inward facing surface of the second vertical wall.

20. 20. The purification method of claim 19, wherein placing the container between the first magnetic field generating element and the second magnetic field generating element comprises horizontally inserting the container through an opening defined between the first vertical wall and the second vertical wall.

21. The purification method according to any one of claims 12 to 20, wherein the first magnetic field generating element comprises a first permanent magnet.

22. 22. The purification method of claim 21, wherein the first permanent magnet has a maximum magnetic attractive force of 100 N or more.

23. 1. A workstation for separating a target material from a medium in which the target material is suspended, the medium being contained in at least one container; a work surface for receiving the at least one container containing the medium; a fluid transfer member configured to transfer fluid to and from the at least one container; an automated manipulator configured to move the fluid transfer member relative to the work surface; a plurality of magnetic field generating elements, each movable relative to the work surface between a first position spaced from the at least one container and a second position proximate the at least one container; Including, workstations.

24. 24. The workstation of claim 23, wherein the plurality of magnetic field generating elements are laterally spaced apart from one another to define a plurality of rows for receiving a plurality of containers including the at least one container.

25. 25. The workstation of claim 24, wherein each of the plurality of magnetic field generating elements has a longitudinal axis, the longitudinal axes of the plurality of magnetic field generating elements being parallel to one another.

26. 26. The workstation of claim 25, wherein each magnetic field generating element of the plurality of magnetic field generating elements has a length parallel to the longitudinal axis and a width perpendicular to the longitudinal axis, the length being equal to or greater than 10 inches and the width being equal to or greater than 0.5 inches.

27. A workstation according to any one of claims 23 to 26, wherein the work surface is arranged horizontally and each magnetic field generating element of the plurality of magnetic field generating elements is horizontally movable.

28. 28. A workstation according to any one of claims 23 to 27, comprising a linear actuator configured to reciprocate at least a first of the plurality of magnetic field generating elements between the first position and the second position.

29. 30. The workstation of claim 28, wherein the linear actuator comprises at least one of a hydraulic cylinder, a pneumatic cylinder, or an electric motor.

30. 30. A workstation according to any one of claims 23 to 29, wherein the automated manipulator is positioned above the work surface and the fluid transfer member is configured to transfer fluid to and from the at least one container through an opening in the top of the at least one container.

31. A workstation according to any one of claims 23 to 30, wherein the automated manipulator comprises a Cartesian robot movable in at least the x and y directions.

32. 32. A workstation according to any one of claims 23 to 31, comprising a pump in fluid communication with the fluid transfer member and configured to add and remove fluid from the at least one container through the fluid transfer member.

33. 33. The workstation of claim 32, wherein the pump is attached to the automated manipulator.

34. 34. A workstation according to any one of claims 32 or 33, comprising a multi-position valve in fluid communication with the pump and configured to selectively couple the pump to at least one of an external fluid source or a drain.

35. 35. A workstation according to any one of claims 23 to 34, comprising a plurality of magnetic beads for submersion in the medium in the at least one container, each magnetic bead of the plurality of magnetic beads having an outer surface configured to temporarily bind to the target substance for separating the target substance from the medium.

36. A workstation according to any one of claims 23 to 13, wherein the fluid transfer member comprises at least two parallel fluid conduits.

37. A workstation according to any one of claims 23 to 36, wherein the first magnetic field generating element comprises a first permanent magnet.

38. 38. A workstation as claimed in claim 37, wherein the first permanent magnet has a maximum magnetic attractive force of 100 N or greater.

39. 1. A purification method comprising the steps of: providing a workstation having a work surface, an automated manipulator movable relative to the work surface to carry a fluid transfer member, and a plurality of magnetic field generating elements spaced laterally from one another and defining a plurality of rows; adding at least one medium having a target substance suspended therein to a plurality of containers; adding a plurality of magnetic beads to the plurality of containers, wherein the target substance temporarily binds to the plurality of magnetic beads; disposing the plurality of vessels in a plurality of rows defined between the plurality of magnetic field generating elements such that the plurality of magnetic field generating elements magnetically attract and hold the plurality of magnetic beads against an interior surface of each vessel of the plurality of vessels; A purification method comprising:

40. 40. The purification method of claim 39, comprising: causing the automated manipulator to insert an end of the fluid transfer member into the at least one medium contained in at least a first container of the plurality of containers; and removing the at least one medium from the first container through the fluid transfer member.

41. 41. The purification method of claim 40, further comprising, after removing the medium from the first container, moving at least a first magnetic field generating element of the plurality of magnetic field generating elements from a first position near the first container to a second position away from the first container.

42. 42. The purification method of claim 41, comprising adding an eluant to the first vessel through the fluid transfer member to elute the target substance bound to the plurality of magnetic beads.

43. 43. The purification method of claim 42, comprising: moving the first magnetic field generating element from the second position to the first position such that the first magnetic field generating element magnetically attracts and holds the plurality of magnetic beads against the interior surface of the first container; and then removing the eluent from the first container through the fluid transfer member.

44. The purification method of any one of claims 41 to 43, comprising adding a wash fluid to the first vessel through the fluid transfer member.

45. 45. The purification method of claim 44, comprising: moving the first magnetic field generating element from the second position to the first position such that the first magnetic field generating element magnetically attracts and holds the plurality of magnetic beads against the interior surface of the first container; and removing the washing fluid from the first container through the fluid transfer member.

46. The purification method according to any one of claims 39 to 45, wherein the plurality of magnetic field generating elements comprises a first permanent magnet.

47. 47. The purification method of claim 46, wherein the first permanent magnet has a maximum magnetic attractive force of 100 N or more.

48. The purification method of any one of claims 39 to 47, wherein the automated manipulator comprises a Cartesian robot movable in at least the x and y directions.

Images