US-12616980-B2 - Magnetic assisted separation apparatuses and related methods

US12616980B2US 12616980 B2US12616980 B2US 12616980B2US-12616980-B2

Abstract

Magnetic assisted separation apparatuses for separating a target substance from a medium in which the target substance is suspended, and related methods, are provided. According to one aspect, a magnetic separator may include a frame having an opening configured to receive one or more containers containing the medium. Additionally, the magnetic separator may include first and second magnetic field generating elements mounted on opposing sides of the frame such that one or more containers can be positioned between the first and second magnetic field generating elements. According to another aspect, a workstation includes a work surface for receiving one or more containers containing the medium, a fluid transfer member, an automated manipulator configured to move the fluid transfer member, and a plurality magnetic field generating elements each being moveable between a position remote from the one or more containers and another position adjacent to the one or more containers.

Inventors

Craig Michael Schulz
Justin James Provchy
John Kasajja Kawooya

Assignees

AMGEN INC.

Dates

Publication Date: 20260505
Application Date: 20220728

Claims (20)

1 . A purification method comprising: adding a medium in which a target substance is suspended to a container; adding a plurality magnetic beads to the container, the target substance temporarily binding to the plurality of magnetic beads; and positioning the container between a first magnetic field generating element mounted on an inwardly facing surface of a first sidewall and a second magnetic field generating element mounted on an inwardly facing surface of a second sidewall, the first and second magnetic field generating elements being held at a distance from each other by a frame including the first sidewall, the second sidewall, and a bottom wall extending between the inwardly facing surface of the first sidewall and the inwardly facing surface of the second sidewall, the first magnetic field generating element comprising a first surface facing the first sidewall and a second surface configured to face the container, wherein the first surface and the second surface of the first magnetic field generating element face in opposite directions, and the second magnetic field generating element comprising a first surface facing the second sidewall and a second surface configured to face the container, wherein the first surface and the second surface of the second magnetic field generating element face in opposite directions, 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 interior surface of the container.
2 . The purification method of claim 1 , wherein positioning 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 of the frame to a second position located between the first and second magnetic field generating elements.
3 . The purification method of claim 1 , comprising removing the medium from the container 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 container.
4 . The purification method of claim 3 , comprising, after removing the medium from the container, adding an eluent to the container to elute the target substance bound to the plurality of magnetic beads and removing the container from between the first and second magnetic field generating elements so that the plurality of magnetic beads are free to disperse in the eluent.
5 . The purification method of claim 4 , comprising repositioning the container between the first and second magnetic field generating elements 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 subsequently removing the eluent from the container.
6 . The purification method of claim 3 , comprising, after removing the medium from the container, adding a washing fluid to the container and removing the container from between the first and second magnetic field generating elements so that the plurality of magnetic beads are free to disperse in the washing fluid.
7 . The purification method of claim 6 , comprising repositioning the container between the first and second magnetic field generating elements 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 subsequently removing the washing fluid from the container.
8 . The purification method of claim 1 , wherein positioning the container between the first magnetic field generating element and the second magnetic field generating element comprises inserting the container in a horizontal direction through an opening defined between the first sidewall and the second sidewall.
9 . The purification method of claim 1 , the first magnetic field generating element including a first permanent magnet.
10 . The purification method of claim 9 , the first permanent magnet having a maximum magnetic pull force equal to or greater than 100 N.
11 . A purification method comprising: providing a workstation having a base including a work surface being horizontally arranged and an interior space vertically below the work surface, an automated manipulator moveable relative to the work surface and carrying a fluid transfer member, a plurality of magnetic field generating elements laterally spaced apart from each other to define a plurality of rows, and a linear actuator positioned at least partially within the interior space of the base at least partially vertically below the work surface; adding at least one medium in which a target substance is suspended to a plurality of containers; adding a plurality of magnetic beads to the plurality of containers, the target substance temporarily binding to the plurality of magnetic beads; arranging the plurality of containers in 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 against an interior surface of a respective container of the plurality of containers; and moving, by motion generated by the linear actuator, at least a first magnetic field generating element of the plurality of magnetic field generating elements in a horizontal direction relative to the work surface.
12 . The purification method of claim 11 , 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 via the fluid transfer member.
13 . The purification method of claim 12 , comprising after removing the medium from the first container, moving at least the first magnetic field generating element of the plurality of magnetic field generating elements from a first position adjacent to the first container to a second position remote from the first container.
14 . The purification method of claim 13 , comprising adding an eluent to the first container via the fluid transfer member to elute the target substance bound to the plurality of magnetic beads.
15 . The purification method of claim 14 , 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 subsequently removing the eluent from the first container via the fluid transfer member.
16 . The purification method of claim 13 , comprising adding a washing fluid to the first container via the fluid transfer member.
17 . The purification method of claim 16 , 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 via the fluid transfer member.
18 . The purification method of claim 11 , the plurality of magnetic field generating elements including a first permanent magnet.
19 . The purification method of claim 18 , the first permanent magnet having a maximum magnetic pull force equal to or greater than 100 N.
20 . The purification method of claim 11 , the automated manipulator including a Cartesian coordinate robot moveable in at least an x-direction and a y-direction.

Description

CROSS-REFERENCE TO RELATED APPLICATION This is a divisional of U.S. patent application Ser. No. 16/018,923, filed June 26 2018, which claims priority to U.S. Provisional Patent Application No. 62/534,563, filed Jul. 19, 2017, the entire contents of each of which are hereby incorporated by reference herein. FIELD OF DISCLOSURE The present disclosure generally relates to separation apparatuses and methods and, more particularly, to separating a target substance such as a biomolecule from a fluid medium in which the target substance is suspended, in order to facilitate downstream processing or analysis of the target substance. BACKGROUND Certain diagnostic, research, and drug manufacturing activities benefit from or require the isolation a target substance, such as a protein, contained in a cell culture or other biological mixture. This task has been accomplished through various techniques in the past. Some of these require altering the solubility of the target substance such that it precipitates out of the biological mixture. Certain other techniques require centrifugation, in which particles of different densities are separated by rotating them about a fixed point at high speeds. Still other techniques are based on chromatography, which requires passing the biological mixture through a filtering material in which the constituent components of the biological mixture move at different rates. Such conventional purification techniques, and others, tend to be time-consuming, labor-intensive, and/or limited to relatively small sample sizes. Centrifugation, for example, is typically carried out in test tubes or bottles, which may limit the volume of material that can be processed at a given time. Also, certain conventional purification techniques may require a laboratory technician to manually pipette fluids between various containers, which can be inefficient and may increase the risk of cross-contamination. The present disclosure sets forth purification related apparatuses and methods embodying advantageous alternatives to existing purification apparatuses and methods, and that may address one or more of the challenges or needs mentioned herein, as well as provide other benefits and advantages. SUMMARY One aspect of the present disclosure provides a magnetic separator for separating or removing a target substance from a medium in which the target substance is suspended. The magnetic separator may include a frame having a first opening configured to receive at the 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 and second magnetic field generating elements may be mounted on opposing sides of the frame at a distance from each other such that the at least one container is positionable between the first and second magnetic field generating elements. 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 container or vessel; (b) adding a plurality magnetic beads to the container, the target substance temporarily binding to the plurality of magnetic beads; and (c) positioning the container between a first magnetic field generating element and a second magnetic field generating element, the first and second magnetic field generating elements being held at a distance from each other by a frame, 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 interior surface of the container. An additional 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 container or vessel containing the medium, and a fluid transfer member configured to transfer fluids to and from the at least one container. Additionally, the workstation may include an automated manipulator configured to move the fluid transfer member relative to the work surface. Moreover, the workstation may include a plurality magnetic field generating elements each being moveable relative to the work surface between a first position remote from the at least one container and a second position adjacent to the at least one container. Yet another aspect of the present disclosure provides a purification method which may include: (a) providing a workstation having a work surface, an automated manipulator moveable relative to the work surface and carrying a fluid transfer member, and a plurality of magnetic field generating elements laterally spaced apart from each other to define a plurality of rows; (b) adding at least one medium in which a target substance is suspended to a plurality of containers or vessels; (c) adding a plurality of magnet