CN-115415047-B - Magnetically assisted separation apparatus and related methods

Abstract

A magnetically assisted separation device and associated method for separating a target substance from a culture medium having the target substance suspended therein 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 culture medium. Further, the magnetic separator may include a first magnetic field generating element and a second magnetic field generating element mounted on opposite sides of the frame such that the one or more containers may be positioned between the first magnetic field generating element and the second magnetic field generating element. According to another aspect, a workstation includes a work surface for receiving one or more containers containing the culture medium, a fluid transfer member, an automated manipulator configured to move the fluid transfer member, and a plurality of magnetic field generating elements, each magnetic field generating element being movable between a first position remote from the one or more containers and a second position adjacent to the one or more containers.

Inventors

• C. M. Scholes
• J. J. plovki
• J.K. Kauya

Assignees

• 美国安进公司

Dates

Publication Date

20260512

Application Date

20180627

Priority Date

20170719

Claims (20)

1. 1. A workstation for separating a target substance from a medium having the target substance suspended therein, the medium being contained in at least one container, the workstation comprising: A base comprising a working surface for receiving the at least one container containing the culture medium, said working surface being horizontally arranged; A fluid transfer member configured to transfer fluid to and from the at least one container; a robotic manipulator configured to move the fluid transfer member relative to the working surface; A peristaltic pump configured to add fluid to and remove fluid from the at least one container via the fluid transfer member; a valve having a plurality of positions, the valve configured to couple the peristaltic pump in fluid communication with at least one external fluid source in a first position and to couple the peristaltic pump in fluid communication with at least one waste container or drain tube in a second position; A plurality of magnetic field generating elements, each magnetic field generating element being movable in a horizontal direction relative to the working surface between a first position away from the at least one container and a second position adjacent the at least one container, and An actuator positioned at least partially vertically below the working surface within the base and configured to move at least a first magnetic field generating element of a plurality of magnetic field generating elements relative to the working surface, Wherein the fluid transfer member, peristaltic pump and valve are mounted on the robotic manipulator such that the fluid transfer member, peristaltic pump and valve move together during movement of the robotic manipulator.
2. 2. The workstation of claim 1, the plurality of magnetic field generating elements being laterally spaced apart from one another to define a plurality of rows for receiving a plurality of containers including the at least one container.
3. 3. The workstation as recited in claim 2, each of the plurality of magnetic field generating elements having a longitudinal axis, the longitudinal axes of the plurality of magnetic field generating elements being parallel to one another.
4. 4. The workstation of claim 3 wherein each of the plurality of magnetic field generating elements has a length parallel to the longitudinal axis and a width perpendicular to the longitudinal axis, wherein the length is greater than or equal to 10 inches and the width is greater than or equal to 0.5 inches.
5. 5. The workstation as recited in any one of claims 1 to 4, wherein the actuator includes a linear actuator configured to reciprocate at least the first magnetic field generating element of the plurality of magnetic field generating elements between the first and second positions.
6. 6. The workstation of claim 5 wherein the linear actuator comprises at least one of a hydraulic cylinder, a pneumatic cylinder, or an electric motor.
7. 7. The workstation of claim 1, the robotic manipulator disposed above the work surface and the fluid transfer member configured to transfer fluid to and from the at least one container via an opening in a top of the at least one container.
8. 8. The workstation of claim 1, the robotic manipulator comprising a cartesian robot movable in at least an x-direction and a y-direction.
9. 9. The workstation of claim 1 wherein said valve is a multi-position valve in fluid communication with the peristaltic pump.
10. 10. The workstation of claim 1 comprising a plurality of magnetic beads for immersion in the medium in the at least one vessel, each magnetic bead of the plurality of magnetic beads having an outer surface configured to temporarily bind the target substance to separate the target substance from the medium.
11. 11. The workstation of claim 1 wherein the fluid transfer member comprises at least two parallel fluid conduits.
12. 12. The workstation as recited in claim 1, the first magnetic field generating element comprising a first permanent magnet.
13. 13. The workstation as recited in claim 12, the first permanent magnet having a maximum magnetic pull equal to or greater than 100N.
14. 14. A purification method comprising: Providing a workstation having a base with a horizontally disposed working surface, an automatic manipulator movable relative to the working surface and carrying a fluid transfer member, a peristaltic pump configured to add fluid to and remove fluid from a plurality of containers via the fluid transfer member, a valve having a plurality of positions, the valve configured to couple the peristaltic pump in fluid communication with at least one external fluid source in a first position and with at least one waste container or drain in a second position, and a plurality of magnetic field generating elements laterally spaced from each other to define a plurality of rows, and an actuator positioned at least partially vertically below the working surface within the base, wherein the fluid transfer member, peristaltic pump and valve are mounted on the automatic manipulator such that the fluid transfer member, peristaltic pump and valve move together during movement of the automatic manipulator; Adding at least one medium having a target substance suspended therein to the 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 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 retain the plurality of magnetic beads against an inner surface of a respective container of the plurality of containers, and At least a first magnetic field generating element of the plurality of magnetic field generating elements is moved in a horizontal direction relative to the work surface.
15. 15. The purification method of claim 14, comprising causing the robotic manipulator to insert an end of the fluid transfer member into at least one culture medium contained in at least a first vessel of the plurality of vessels and remove the at least one culture medium from the first vessel via the fluid transfer member.
16. 16. The purification method of claim 15, comprising moving at least a first magnetic field generating element of the plurality of magnetic field generating elements from a first position adjacent the first container to a second position remote from the first container after removing the at least one culture medium from the first container.
17. 17. The purification method of claim 16, 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.
18. 18. The purification method of claim 17, 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 an inner surface of the first container, followed by removing the eluate from the first container via the fluid transfer member.
19. 19. The purification method of any one of claims 16 to 18, comprising adding a washing fluid to the first vessel via the fluid transfer member.
20. 20. The purification method of claim 19, 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 an inner surface of the first container and removes the washing fluid from the first container via the fluid transfer member.

Description

Magnetically assisted separation apparatus and related methods Cross Reference to Related Applications The present application claims priority from U.S. provisional patent application No. 62/534,563 filed on 7, 19, 2017, which is incorporated herein by reference in its entirety. Technical Field The present disclosure relates generally to separation devices and methods, and more particularly to separating a target substance (such as a biomolecule) from a fluid medium having the target substance suspended therein, in order to facilitate downstream processing or analysis of the target substance. Background Certain diagnostic, research and pharmaceutical production activities benefit from or require 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 techniques require changing the solubility of the target substance to precipitate it from the biological mixture. Some other techniques require centrifugation, in which particles of different densities are separated by rotating them at high speed about a fixed point. Still other techniques are based on chromatography, which entails passing a biological mixture through a filter material in which the constituent components of the biological mixture move at different rates. Such conventional purification techniques and other techniques 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. Moreover, certain conventional purification techniques may require laboratory technicians to manually aspirate fluids between various containers, which may be inefficient and may increase the risk of cross-contamination. The present disclosure sets forth apparatus and methods relating to purification that implement advantageous alternatives to existing purification apparatus and methods and that address one or more of the challenges or needs mentioned herein as well as provide other benefits and advantages. Disclosure of Invention An 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 least one container or vessel containing a culture medium. The magnetic separator may further 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 the at least one container can be positioned between the first magnetic field generating element and the second magnetic field generating element. Another aspect of the present disclosure provides a purification method that may include (a) adding a medium having a target substance suspended therein to a container or vessel, (b) adding a plurality of magnetic beads to the container, the target substance temporarily binding the plurality of magnetic beads, and (c) positioning the container between a first magnetic field generating element and a second magnetic field generating element that are 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 inner surface of the container. Additional aspects of the present disclosure provide a workstation for separating a target substance from a medium having the target substance suspended therein. The workstation may include a working surface for receiving at least one container or vessel containing the culture medium, a fluid transfer member configured to transfer fluid to and from the at least one container. Further, the workstation may include a robotic manipulator configured to move the fluid transfer member relative to the work surface. Furthermore, the workstation may comprise a plurality of magnetic field generating elements, each magnetic field generating element being movable relative to the work surface between a first position remote from the at least one container and a second position adjacent the at least one container. Yet another aspect of the disclosure provides a purification method that may include (a) providing a workstation having a working surface, an automatic manipulator movable relative to the working surface and carrying a fluid transfer member, and a plurality of magnetic field generating elements laterally spaced apart from one another to define a plurality of rows, (b) adding at least one culture medium having a target substance suspended therein to a plurality of co