Biomolecule extraction apparatus and methods

Abstract

The application provides a biomolecule extraction device and method, the biomolecule extraction device comprises: a container provided with a plurality of accommodation holes; magnetic beads placed in the accommodation holes; a primary magnetic field device comprising a primary magnet arranged outside the container; a secondary magnet placed in the accommodation holes, the secondary magnet can be magnetized and demagnetized by the primary magnet; wherein the secondary magnet can attract the magnetic beads when magnetized by the primary magnet, and the movement of the primary magnet can drive the secondary magnet with the attracted magnetic beads to move into another accommodation hole, and the magnetic beads are dispersed in the solution in the accommodation hole after the primary magnet demagnetizes the secondary magnet; the secondary magnet is a cylindrical magnet, the direction of the magnetic pole of the primary magnet is parallel to the wall surface contacted during the movement, and the secondary magnet rolls along the wall surface with the magnetic beads during the movement of the primary magnet with the secondary magnet. The scheme provided by the application can solve the problems of additional consumables and easy sample contamination in the biomolecule extraction method in the prior art.

Description

TECHNICAL FIELD

[0001] The present disclosure relates to the field of biomolecule extraction, and in particular to a biomolecule extraction device and method. BACKGROUND

[0002] One of the methods for biomolecule purification or extraction is to use nanometer magnetic beads as carriers to separate biomolecules attached to the surface of the magnetic beads from impurities in the original sample under the action of a magnetic field. For example, the most common method used in magnetic nucleic acid purification technology is to use silica-coated magnetic beads, in which nucleic acids are combined with magnetic beads in a high-salt solution, and the magnetic beads are collected by applying a magnetic field, so that the nucleic acids are separated from other cell components or sample impurities, and finally a low-salt buffer is used to elute the purified nucleic acids.

[0003] Currently, there are two specific ways for biomolecule purification or extraction:

[0004] 1. A magnet placed outside the container attracts the magnetic beads to the inner wall of the container, and then a pipette is used to replace the liquid in the container to remove the solution containing contaminants, and the above steps are repeated to clean the magnetic beads and elute the nucleic acids from the magnetic beads.

[0005] 2. A magnetic rod placed inside the container and directly connected to the outside machinery attracts the magnetic beads, and then the magnetic rod is moved to move the magnetic beads from one container to another, so that the magnetic beads are separated from the solution containing contaminants, and the above steps are repeated to clean the magnetic beads and elute the nucleic acids from the magnetic beads.

[0006] However, the current biomolecule extraction method has the following defects: additional consumables are needed to transport the magnetic beads (magnetic rod sleeve) or to transport the liquid (pipette tip), and in addition, a mechanical arm is needed for magnetic rod movement or liquid processing, i.e. peripheral devices (magnetic rod, pipette tip, etc.) need to enter the solution container, which has the risk of instrument structure being bulky and contaminating the sample. SUMMARY

[0007] The embodiments of the present application provide a biomolecule extraction device and a biomolecule extraction method to solve the defects in the current biomolecule extraction method.

[0008] The embodiments of the present application provide a biomolecule extraction device, comprising:

[0009] a container provided with a plurality of accommodation holes, and a communication channel is arranged between each adjacent two accommodation holes;

[0010] magnetic beads for being placed in the accommodation holes to adsorb biomolecules in the solution in the accommodation holes;

[0011] a primary magnetic field device comprising a primary magnet movably arranged outside the container;

[0012] A secondary magnet is placed in the receiving hole, the secondary magnet being configured to be magnetized and demagnetized by the primary magnet;

[0013] The secondary magnet is magnetized by the primary magnet to attract the magnetic beads, and the movement of the primary magnet can drive the secondary magnet with the attracted magnetic beads to move into another receiving hole. After the primary magnet demagnetizes the secondary magnet, the magnetic beads are dispersed in the solution in the receiving hole. The secondary magnet is a cylindrical magnet, and the primary magnet is configured such that its magnetic poles are parallel to the wall surface it contacts during movement, so that as the primary magnet moves with the secondary magnet, the secondary magnet carries the magnetic beads and rolls along the wall surface.

[0014] In one embodiment, the primary magnet is configured to make line contact or surface contact with the wall surface it contacts during the movement of the secondary magnet.

[0015] In one embodiment, the container includes a container body and a container lid covering the container body. The container body is provided with a plurality of receiving holes, and the container lid is configured to cover the plurality of receiving holes.

[0016] In one embodiment, a partition wall is provided between two adjacent receiving holes, and the container cover includes a cover plate body covering the top of the receiving hole and baffles disposed on the inner side of the cover plate body and respectively corresponding to the partition wall;

[0017] The container lid is configured to have a first position and a second position when it is placed on the container body. In the second position, a gap is formed between the baffle and the corresponding partition wall, and the gap forms a connecting channel between the two receiving holes. In the first position, the baffle moves down to the partition wall and closes the connecting channel.

[0018] In one embodiment, the primary magnet includes a permanent magnet and an electromagnet, with the magnetic poles of the permanent magnet and the electromagnet set to be parallel. By controlling the direction of the current, the magnetic poles of the electromagnet can be made to be opposite to or in the same direction as the magnetic poles of the permanent magnet.

[0019] In one embodiment, the primary magnetic field device further includes a mounting frame, a vertically movable slider, and a horizontally movable slider, wherein the primary magnet is mounted on the vertically movable slider; wherein the horizontally movable slider is configured to move horizontally relative to the mounting frame, and the vertically movable slider is configured to slide vertically relative to the horizontally movable slider.

[0020] A rotation drive mechanism is also provided between the up-and-down moving slider and the primary magnet, and the rotation drive mechanism is configured to drive the primary magnet to rotate relative to the up-and-down moving slider.

[0021] Embodiments of this application also provide a method for biomolecule extraction, the method comprising:

[0022] The magnetic beads and the solution containing biomolecules are placed in the first receiving hole of the container, so that the biomolecules bind to the magnetic beads.

[0023] A primary magnet is used to magnetize a secondary magnet located within a first receiving hole, causing the secondary magnet to attract a magnetic bead; wherein the primary magnet is located outside the first receiving hole.

[0024] Move the primary magnet so that the secondary magnet, carrying the magnetic bead, moves along the container wall into the second receiving hole of the container;

[0025] The secondary magnet is demagnetized, causing the magnetic beads on the secondary magnet to disperse in the solution in the second receiving hole;

[0026] A primary magnet is used to magnetize a secondary magnet located in the second receiving hole, so that the secondary magnet attracts the magnetic bead.

[0027] Move the primary magnet so that the secondary magnet, carrying the magnetic bead, moves along the container wall into the third receiving hole of the container;

[0028] The secondary magnet is demagnetized, causing the magnetic beads on the secondary magnet to disperse in the solution in the third receiving hole;

[0029] During the movement of the primary magnet carrying the secondary magnet, the primary magnet rests against the container wall with its magnetic poles parallel to the container wall; the secondary magnet is cylindrical, and during the movement of the primary magnet carrying the secondary magnet, the secondary magnet carries the magnetic bead and rolls along the container wall.

[0030] The biomolecule extraction device provided in the embodiments of this application uses a method of transferring magnetic beads adsorbed with biomolecules by moving a secondary magnet in a container through a primary magnet. This can solve the problems of increased cost due to the need for additional consumables and easy sample contamination in the prior art, which uses a pipette to replace the liquid in the container or a magnetic rod to transport the magnetic beads.

[0031] Other features and advantages of this application will be set forth in the following description, and will be apparent in part from the description, or may be learned by practicing the application. Other advantages of this application can be realized and obtained by means of the embodiments described in the description and the accompanying drawings. Attached Figure Description

[0032] The accompanying drawings are used to provide an understanding of the technical solutions of this application and constitute a part of the specification. They are used together with the embodiments of this application to explain the technical solutions of this application and do not constitute a limitation on the technical solutions of this application.

[0033] Figure 1 This is a schematic diagram of a biomolecule extraction device according to one embodiment of the present application, wherein magnetic beads are dispersed in a solution in a first receiving hole;

[0034] Figure 2 for Figure 1 A schematic diagram of the biomolecule extraction device in the diagram, cut across the first receiving hole;

[0035] Figure 3 This is a schematic diagram of the structure of a biomolecule extraction device according to one embodiment of the present application, wherein the magnetic beads in the first receiving hole are attracted by a secondary magnet;

[0036] Figure 4 for Figure 3 A schematic diagram of the biomolecule extraction device in the diagram, cut across the first receiving hole;

[0037] Figure 5 This is a schematic diagram of a biomolecule extraction device according to one embodiment of the present application, wherein a secondary magnet is transferred into a second receiving hole and magnetic beads are dispersed in a solution;

[0038] Figure 6 for Figure 5 A schematic diagram of the biomolecule extraction device in the middle, cut at the second receiving hole;

[0039] Figure 7 This is a schematic diagram of a secondary magnet with magnetic beads attracted to a primary magnet and attached to the container wall according to one embodiment of the present application (the magnetic poles of the primary magnet are parallel to the surface of the medium).

[0040] Figure 8 This is a schematic diagram of a secondary magnet with magnetic beads attracted to a primary magnet and attached to the container wall according to another embodiment of this application (the magnetic poles of the primary magnet are perpendicular to the surface of the medium).

[0041] Figure 9 This is a schematic diagram of a structure according to one embodiment of the present application, in which the primary magnet is in line contact with the surface of the dielectric and the magnetic pole direction of the primary magnet is parallel to the surface of the dielectric.

[0042] Figure 10 Showing Figure 9 A top view of the structure shown;

[0043] Figure 11 This is a schematic diagram of a structure according to one embodiment of the present application, in which the primary magnet is in surface contact with the dielectric surface and the magnetic pole direction of the primary magnet is parallel to the dielectric surface;

[0044] Figure 12 for Figure 11 A top view of the structure shown;

[0045] Figure 13 This is a schematic diagram of a structure according to one embodiment of the present application, in which the primary magnet is in surface contact with the dielectric surface and the magnetic pole direction of the primary magnet is perpendicular to the dielectric surface;

[0046] Figure 14 for Figure 13 A top view of the structure shown;

[0047] Figure 15 This is a schematic diagram of the structure of a primary magnet according to one embodiment of this application;

[0048] Figure 16 for Figure 15 A diagram showing the primary magnet viewed from one side;

[0049] Figure 17 for Figure 15 The diagram shows the primary magnet as viewed from one end;

[0050] Figure 18 This is a schematic diagram of the structure of a secondary magnet according to one embodiment of this application;

[0051] Figure 19 This is a schematic diagram illustrating the state in which the electromagnet and the permanent magnet in the primary magnet are in the same direction, thereby attracting the secondary magnet, according to one embodiment of this application.

[0052] Figure 20 This is a schematic diagram showing the state in which the electromagnet and the permanent magnet in the primary magnet are reversed, thereby causing the secondary magnet to detach, according to one embodiment of this application.

[0053] Figure 21 This is a schematic diagram of the structure of a primary magnetic field device according to one embodiment of this application;

[0054] Figure 22 This is a schematic diagram of the structure of the primary magnetic field device and the container in one embodiment of this application;

[0055] Figure 23 This is a schematic diagram of the primary magnetic field device according to another embodiment of this application;

[0056] Figure 24 This is a schematic diagram of the primary magnetic field device according to another embodiment of the present application.

[0057] Explanation of reference numerals in the attached figures:

[0058] 1-Container; 11-Container body; 111-Outer wall; 112-Separation wall; 12-Container lid; 121-Lid plate body; 122-Baffle; 13-Accommodation hole; 13a-First accommodation hole; 13b-Second accommodation hole; 13c-Third accommodation hole; 14-Connecting channel; 2-Magnetic bead; 3-Primary magnetic field device; 31-Primary magnet; 311-Permanent magnet; 312-Electromagnet; 313-Magnetic conductor; 3131-Magnetic plate; 3132-Magnetic field focusing end; 32-Motor; 33-Up-down moving slider; 34-Horizontal moving slider; 4-Secondary magnet. Detailed Implementation

[0059] This application describes several embodiments, but these descriptions are exemplary and not limiting, and it will be apparent to those skilled in the art that many more embodiments and implementations are possible within the scope of the embodiments described herein. Although many possible combinations of features are shown in the drawings and discussed in the detailed description, many other combinations of the disclosed features are also possible. Unless specifically limited, any feature or element of any embodiment may be used in combination with, or may replace, any feature or element of any other embodiment.

[0060] This application includes and contemplates combinations of features and elements known to those skilled in the art. The embodiments, features, and elements disclosed in this application can also be combined with any conventional features or elements to form unique inventive solutions. Any feature or element of any embodiment can also be combined with features or elements from other inventive solutions to form another unique inventive solution. Therefore, it should be understood that any feature shown and / or discussed in this application can be implemented individually or in any suitable combination. Therefore, the embodiments are not limited except by the limitations imposed by the appended claims and their equivalents. Furthermore, various modifications and changes can be made within the scope of the appended claims.

[0061] Furthermore, in describing representative embodiments, the specification may have presented methods and / or processes as a specific sequence of steps. However, the method or process should not be limited to the specific order of steps described herein, to the extent that it does not depend on such a specific order. As will be understood by those skilled in the art, other sequences of steps are also possible. Therefore, the specific order of steps set forth in the specification should not be construed as a limitation of the claims. Moreover, the claims concerning the method and / or process should not be limited to the steps performed in the written order, and those skilled in the art will readily understand that these orders can be varied and still remain within the spirit and scope of the embodiments of this application.

[0062] Embodiments of this application provide a biomolecule extraction device, such as... Figures 1-6 In one embodiment, the biomolecule extraction device includes: a container 1, magnetic beads 2, a primary magnetic field device 3, and a secondary magnet 4.

[0063] The container 1 is provided with a plurality of receiving holes 13, and there is a connecting channel 14 between each pair of adjacent receiving holes 13; magnetic beads 2 are used to be placed in the receiving holes 13 to adsorb biomolecules in the solution in the receiving holes 13; the primary magnetic field device 3 includes a primary magnet 31 movably disposed on the outside of the container 1; a secondary magnet 4 is used to be placed in the receiving holes 13, and the secondary magnet 4 is configured to be magnetized and demagnetized by the primary magnet 31, and the secondary magnet 4 can be made of a high permeability material such as soft iron or silicon steel.

[0064] In this system, the secondary magnet 4 is magnetized by the primary magnet 31 and can attract the magnetic beads 2. The movement of the primary magnet 31 can move the secondary magnet 4 into another receiving hole 13. After the primary magnet 31 demagnetizes the secondary magnet 4, the magnetic beads 2 disperse in the solution within the receiving hole 13. The secondary magnet 4 is a cylindrical magnet, and the magnetic beads 2 are attracted to both ends of the secondary magnet 4. The primary magnet 31 is configured such that its magnetic poles are parallel to the wall surface it contacts during movement, so that as the primary magnet 31 moves with the secondary magnet 4, the secondary magnet 4 carries the magnetic beads 2 and rolls along the wall surface. The magnetic pole direction refers to the direction from the S pole to the N pole or from the N pole to the S pole of the magnet.

[0065] Figures 1-6 The container 1 is shown to have multiple receiving holes 13, including a first receiving hole 13a, a second receiving hole 13b, a third receiving hole 13c, etc.

[0066] Figure 1 and Figure 2 The diagram shows a first receiving hole 13a containing magnetic beads 2 and a solution containing biomolecules. Within this first receiving hole 13a, the magnetic beads 2 and the biomolecules combine to form a complex. The magnetic beads 2 can be superparamagnetic beads. When an external magnetic field is present, the superparamagnetic beads are magnetized and attracted to both ends of the secondary magnet 4. When no external magnetic field is present, the superparamagnetic beads are easily demagnetized due to thermodynamic effects, exhibiting no hysteresis and not agglomerating; they can disperse in the solution. Furthermore, superparamagnetic beads are more easily magnetized and have a stronger attraction than paramagnetic beads.

[0067] In this application, biomolecular binding refers to the non-covalent binding of a biomolecule with another object, such as adsorption, including physical adsorption, chemical adsorption, affinity adsorption, etc.

[0068] Figure 3 and Figure 4The diagram shows a primary magnet 31 magnetizing a secondary magnet 4, with the secondary magnet 4 attracting the magnetic bead 2 in the first receiving hole 13a. As the primary magnet 31 moves upward, the secondary magnet 4 follows and rolls upward along the container wall. After rolling upward and passing through the connecting channel between the first receiving hole 13a and the second receiving hole 13b, the secondary magnet 4 enters the second receiving hole 13b to further wash the biomolecules through the solution in the second receiving hole 13b.

[0069] Figure 5 and Figure 6 The diagram shows the state of the secondary magnet 4 after it enters the second receiving hole 13b, after which the secondary magnet 4 is demagnetized and the magnetic beads 2 are dispersed in the solution.

[0070] The biomolecule extraction device provided in this application uses a primary magnet 31 to move a secondary magnet 4 within a container to transfer magnetic beads 2 adsorbed with biomolecules. This solves the problems of increased costs due to additional consumables and sample contamination associated with existing methods that use pipettes to replace liquid in the container or magnetic rods to transport magnetic beads. Furthermore, because the secondary magnet 4 carries the magnetic beads 2 and rolls along the wall, its movement efficiency is high, effectively improving the extraction efficiency of biomolecules.

[0071] Figure 7 In the example shown, the secondary magnet 4 is a cylindrical magnet, and the magnetic pole direction of the primary magnet 31 is parallel to the wall surface it contacts. Thus, when the primary magnet 31 applies a magnetic field, the secondary magnet 4 is magnetized, and the magnetic beads 2 are attracted to both ends of the secondary magnet 4. The axis of the secondary magnet 4, i.e., the magnetic field pole direction, is parallel to the wall surface. During the process of the primary magnet 31 driving the secondary magnet 4 to move, the secondary magnet 4 can roll along the wall surface. The magnetic beads 2 attracted to both ends of the secondary magnet 4 do not rub against the wall surface, so the loss of the magnetic beads is small.

[0072] It is understandable that the secondary magnet 4 is cylindrical so that it can roll during movement. In other embodiments, the secondary magnet 4 may be of other shapes, such as square. However, a square secondary magnet 4 may have high frictional resistance when moving along a wall.

[0073] exist Figure 8 In the example, the magnetic pole direction of the primary magnet 31 is perpendicular to the contacted container wall. When the primary magnet 31 applies a magnetic field, the magnetic beads 2 are attracted to both ends of the secondary magnet 4, and the magnetic pole direction of the secondary magnet 4 is perpendicular to the wall. During the process of the primary magnet 31 driving the secondary magnet 4 to move, one end face of the secondary magnet 4 contacts the wall. The magnetic beads 2 on this end face will be lost during the movement. Moreover, the secondary magnet 4 moves along the wall rather than rolling during the movement, which also has the problem of large movement resistance.

[0074] In some examples, the secondary magnet 4 is a cylindrical magnet, and the magnetic pole direction of the primary magnet 31 is parallel to the wall surface it contacts. The primary magnet 31 is configured to make line contact or surface contact with the wall surface it contacts while moving the secondary magnet 4.

[0075] like Figure 9 and Figure 10 In the example, the magnetic pole direction of the primary magnet 31 is parallel to the wall surface it contacts, and the primary magnet 31 and the wall surface are in line contact. Thus, when the magnetized secondary magnet 4 is attracted to the wall surface, its axial direction (i.e., the induced secondary magnetic field polarity) is parallel to the wall surface, allowing the secondary magnet 4 to roll along the wall. Because the primary magnet 31 and the wall surface are in line contact, the magnetic lines of force are relatively concentrated, resulting in a greater guiding force on the secondary magnet 4. Consequently, the secondary magnet 4 rolls well under the influence of the primary magnet 31, achieving high movement efficiency, and minimizing the loss of the magnetic bead 2.

[0076] exist Figure 11 and Figure 12 In the example, the magnetic pole direction of the primary magnet 31 is parallel to the wall surface it contacts, and the primary magnet 31 makes surface contact with the wall surface. Compared with line contact, the secondary magnet 4 jumps during movement due to surface contact between the primary magnet 31 and the wall surface, making it less stable than line contact.

[0077] exist Figure 13 and Figure 14 In the example, the magnetic pole direction of the primary magnet 31 is perpendicular to the wall it is in contact with. Thus, when the secondary magnet 4 is attracted to the wall, its axis (i.e., the magnetic field direction) is perpendicular to the wall it is in contact with. As a result, the magnetic bead 2 on the end of the secondary magnet 4 near the wall will fall off during movement, and the movement resistance of the secondary magnet 4 is large.

[0078] In one embodiment, the container 1 includes a container body 11 and a container lid 12 covering the container body 11. The container body 11 is provided with a plurality of receiving holes 13, and the container lid 12 is configured to cover the plurality of receiving holes 13. By providing the container lid 12, the problem of the prior art where the container is not sealed, the magnetic beads 2 are exposed, and aerosols are easily generated or come into contact with other samples can be solved.

[0079] In one example, reference Figures 1-6 The container body 11 includes an outer wall 111 and a partition wall 112 disposed between two adjacent receiving holes 13. The container cover 12 is configured to include a cover plate body 121 covering the top of the receiving hole 13 and baffles 122 disposed on the inner side of the cover plate body 121 and respectively corresponding to the partition walls 112.

[0080] The container lid 12 is configured to have a first position and a second position when it is placed on the container body 11, with the first position below the second position. In the second position, a gap is formed between the baffle 122 and the corresponding partition wall 112, which forms a connecting channel 14 between the two receiving holes 13. In the first position, the baffle 122 moves down to the partition wall 112 and closes the connecting channel 14.

[0081] Since each well 13 contains a different reagent that cannot be mixed, the connecting channels 14 between the wells need to be closed during transportation. During biomolecule extraction, the magnetic beads 2 carry biomolecules from one well to another for different purposes, such as binding to biomolecules, removing impurities, and releasing biomolecules. Closing the connecting channels 14 prevents the mixing of reagents in different wells, so as not to affect the purity of the final biomolecules.

[0082] In some embodiments, the primary magnet 31 may be a permanent magnet or an electromagnet.

[0083] In another embodiment, such as Figures 15-17 As shown, the primary magnet 31 includes a permanent magnet 311 and an electromagnet 312. The permanent magnet 311 and the electromagnet 312 are configured with parallel magnetic pole directions. By controlling the direction of the current, the magnetic poles of the electromagnet 312 can be made to be opposite to or in the same direction as the magnetic poles of the permanent magnet 311.

[0084] The primary magnet 31 controls the magnetic field strength by controlling the current in the electromagnet 312, thus facilitating the magnetization and demagnetization of the secondary magnet 4. When the magnetic poles of the electromagnet 312 and the permanent magnet 311 are opposite in direction, their magnetic fields cancel each other out, resulting in a weak or non-existent magnetic field generated by the primary magnet 31. When the magnetic poles of the electromagnet 312 and the permanent magnet 311 are in the same direction, their magnetic fields superimpose, resulting in a stronger magnetic field generated by the primary magnet 31. Furthermore, the magnetic field strength of the electromagnet 312 can be altered by controlling the current intensity of the electromagnet 312. For example, when there is no current in the electromagnet 312, the magnetic field generated by the primary magnet 31 weakens.

[0085] In the process of demagnetizing the secondary magnet 4 and dispersing the magnetic beads 2 in the solution, the magnetic field strength of the primary magnet 31 can be controlled to make the secondary magnet 4 attract and detach from the primary magnet 31 rapidly and repeatedly, thereby creating turbulence in the liquid phase, which facilitates the mixing of liquid phase components and the dispersion of the magnetic beads 2.

[0086] The primary magnet 31 may further include a magnetic conductor 313, with an electromagnet 312 and a permanent magnet 311 fixed on the magnetic conductor 313. One end of the magnetic conductor 313 is formed as a magnetic field focusing end 3132 for magnetizing the secondary magnet 4. The magnetic conductor 313 can be made of a high-permeability material such as soft iron or silicon steel. The permeability of the magnetic conductor 313 is much higher than that of the surrounding air or other media. Magnetic lines of force will preferentially propagate along the path of the magnetic conductor 313, thereby changing the original propagation direction of the magnetic lines of force. Therefore, by setting appropriate materials, shapes, and sizes for the magnetic conductor 313, the magnetic flux density of the primary magnet 31 can be increased at the magnetic field focusing end 3132 to increase the magnetic field strength in its vicinity, i.e., focusing, thereby effectively magnetizing the secondary magnet 4.

[0087] like Figures 15-17 In the example shown, the magnetic conductor 313 includes two parallel magnetic plates 3131. An electromagnet 312 and a permanent magnet 311 are fixed between the two magnetic plates 3131, and the magnetic poles of both the electromagnet 312 and the permanent magnet 311 are oriented from one magnetic plate 3131 towards the other. One end of each magnetic plate 3131 forms a magnetic field focusing end 3132. Thus, the magnetic field generated by the magnetic field focusing end 3132 is directed from one magnetic plate 3131 towards the other. When the magnetic field focusing end 3132 abuts against a medium surface (e.g., the container wall of container 1), the magnetic pole direction of the magnetic field focusing end 3132 can be parallel to the abutting medium surface. Figure 19 and Figure 20 As shown, the magnetic poles of the secondary magnet 4, magnetized by the primary magnet 31, are also parallel to the surface of the medium. Magnetic beads 2 can gather at both ends of the magnetic poles of the secondary magnet 4. When the secondary magnet 4 has a cylindrical structure, the primary magnet 31 can drive the secondary magnet 4 to roll along the surface of the medium. The secondary magnet 4 and the attracted magnetic beads 2 experience minimal friction with the surface of the medium, resulting in minimal bead loss and high movement efficiency. Figure 19 This demonstrates how the magnetic force of the primary magnet 31 strengthens the magnetization of the secondary magnet 4, causing the secondary magnet 4 to move towards the primary magnet 31 until it is attracted to the surface of the medium. Figure 20 This shows the state where the magnetic force of the primary magnet 31 cancels out, causing the secondary magnet 4 to demagnetize and move away from the primary magnet 31.

[0088] In one example, the magnetic field focusing end 3132 is configured with a tapered cross-section along the direction toward the end. Since a smaller cross-sectional area results in a larger magnetic flux density for the same magnetic flux, by setting the cross-section of the magnetic field focusing end 3132 to be tapered, the magnetic flux density at the magnetic field focusing end 3132 can be made greater, and the corresponding magnetic field stronger.

[0089] like Figure 16 and Figure 17In the example, the two side surfaces of each magnetic conductive plate 3131 are inclined towards each other in the direction towards the end so that the cross-section tapers, and the two side surfaces of each magnetic conductive plate 3131 are inclined towards each other in the direction between the two magnetic conductive plates 3131, so that the end face forms a trapezoidal end face, and the small ends of the trapezoidal end faces of the two magnetic conductive plates 3131 face each other. That is, the end face area of the two magnetic conductive plates 3131 near the middle position is smaller, so that the magnetic lines of force gather towards the middle position.

[0090] In Figure 16 and Figure 17 In the example of, the gap width A between the two magnetic conductive plates 3131 is less than 3L, preferably, A = L; the minimum width C of the two trapezoidal end faces of the magnetic field focusing end 3132 is less than 3D. Wherein, L is the length of the cylindrical secondary magnet 4 to be magnetized, D is the diameter of the secondary magnet 4, and D < L, referring to Figure 18 the secondary magnet 4 shown in, wherein, the two ends of the secondary magnet 4 are flat or hemispherical.

[0091] The size of the magnetic conductor 313 is specifically set according to the size of the secondary magnet 4, so that the primary magnet 31 is more suitable for magnetizing and transferring the secondary magnet 4.

[0092] Among them, the stronger the magnetic field of the primary magnet 31, the stronger the induced secondary magnetic field; when the primary magnet 31 has a strong magnetic field, the secondary magnet 4 is first attracted to the position closest to the primary magnet 31, and at this time the secondary magnet 4 is further magnetized; the induced secondary magnetic field attracts the magnetic beads 2 in the solution to both ends of the secondary magnet 4, that is, the two poles of the secondary magnetic field.

[0093] Under the action of a strong primary magnetic field, the speed at which the primary magnet 31 attracts the secondary magnet 4 to approach each other or the speed at which the secondary magnet 4 separates from the primary magnet 31 due to gravity in the absence of a primary magnetic field is faster than the speed at which the secondary magnet 4 attracts the magnetic beads 2 to both ends of the secondary magnet 4. After the secondary magnet 4 is attracted to the focused strong magnetic field of the primary magnet 31, the induced secondary magnetic field will attract the magnetic beads 2 in the solution to achieve the purpose of attracting the magnetic beads 2 to both ends of the secondary magnet 4.

[0094] In one embodiment, as Figures 21-24 shown, the primary magnetic field device 3 further includes a mounting rack, an up and down moving slider 33 and a horizontal moving slider 34, and the primary magnet 31 is mounted on the up and down moving slider 33; wherein, the horizontal moving slider 34 is arranged to be able to move horizontally relative to the mounting rack, and the up and down moving slider 33 is arranged to be able to slide up and down relative to the horizontal moving slider 34.

[0095] The primary magnetic field device 3 provided in this application can drive the primary magnet 31 to move up and down and horizontally, thereby enabling the movement of the primary magnet 31 through the primary magnetic field device 3, thus automating the movement of the secondary magnet 4 during the biomolecule extraction process.

[0096] In one embodiment, a rotation drive mechanism is provided between the primary magnet 31 and the vertically movable slider 33. The rotation drive mechanism is configured to drive the primary magnet 31 to rotate. This rotation drive mechanism can be a motor 32, which drives the primary magnet 31 to rotate. The rotation of the primary magnet 31 can influence the rotation direction of the secondary magnet 4, making it more suitable for moving along a predetermined direction.

[0097] In one embodiment, one or more primary magnets 31 may be provided on the up-and-down movable slider 33, and a rotation mechanism may be provided between each primary magnet 31 and the up-and-down movable slider 33.

[0098] like Figure 21 and Figure 22 The primary magnetic field device 3 has a primary magnet 31 mounted on its up-and-down sliding block 33. Figure 22 The primary magnet 31 is shown abutting against the outer wall of the container 1, which has multiple receiving holes.

[0099] Figure 23 and Figure 24 The slide block 33, which moves up and down, is equipped with four primary magnets 31. Figure 23 The image shows that four motors 32 are arranged in an array on the up-and-down sliding slider 33, and each motor is connected to a primary magnet 31. Figure 24 The diagram shows that the vertically moving slider 33 is equipped with two motors 32, each with a primary magnet 31 connected to both ends. Of course, the vertically moving slider 33 can also be equipped with other numbers of primary magnets 31. Each primary magnetic field device 3 can have multiple primary magnets 31, allowing for the simultaneous extraction of biomolecules from multiple samples.

[0100] Embodiments of this application also provide a method for extracting biomolecules, the method comprising:

[0101] The magnetic bead 2 and the solution containing biomolecules are placed in the first receiving hole 13a of the container 1, so that the biomolecules bind to the magnetic bead 2.

[0102] A primary magnet 31 is used to magnetize a secondary magnet 4 located in the first receiving hole 13a, so that the secondary magnet 4 attracts the magnetic bead 2; wherein, the primary magnet 31 is located outside the first receiving hole 13a.

[0103] The primary magnet 31 is moved so that the secondary magnet 4, carrying the magnetic bead 2, moves along the container wall into the second receiving hole 13b of the container 1, while the solution containing impurities remains in the first receiving hole 13a.

[0104] The secondary magnet 4 is demagnetized, so that the magnetic beads 2 on the secondary magnet 4 are dispersed in the solution in the second receiving hole 13b, so that the magnetic beads 2 are in full contact with the solution in the second receiving hole 13b, and the biomolecules on the magnetic beads 2 are dispersed in the solution to perform a second washing of the biomolecules.

[0105] A primary magnet 31 is used to magnetize a secondary magnet 4 located in the second receiving hole 13b, so that the secondary magnet 4 attracts the magnetic bead 2.

[0106] Move the primary magnet 31 so that the secondary magnet 4, carrying the magnetic bead 2, moves along the container wall into the third receiving hole 13c of the container 1.

[0107] The secondary magnet 4 is demagnetized, so that the magnetic beads 2 on the secondary magnet 4 are dispersed in the solution in the third receiving hole 13c, so as to further elute the biomolecules.

[0108] Of course, the magnetic beads 2 with adsorbed biomolecules can be further transferred to the fourth receiving hole by the secondary magnet 4.

[0109] In some embodiments, during the movement of the primary magnet 31 carrying the secondary magnet 4, the primary magnet 31 is attached to the container wall and the magnetic pole direction is parallel to the container wall.

[0110] The secondary magnet 4 is cylindrical. As the primary magnet 31 moves with the secondary magnet 4, the secondary magnet 4 carries the magnetic bead 2 and rolls along the container wall.

[0111] The biomolecule extraction method provided in this application can be performed using the biomolecule extraction equipment described above.

[0112] In the description of this application, biomolecules may include nucleic acid molecules, such as ribonucleic acid (RNA) and deoxyribonucleic acid (DNA), protein molecules, such as antibody molecules, antigen molecules, biological enzymes, receptors, growth factors, and other organic molecules that originate from or are related to or can act on organisms.

[0113] In this application, the terms attraction, adsorption, and binding are used interchangeably, and their specific meanings depend on the context. Generally speaking, attraction can be an interaction that occurs before or after physical contact between two objects, while adsorption and binding are effects or processes that occur after physical contact. Adsorption of biomolecules can include physical adsorption, chemisorption, affinity adsorption, etc.

[0114] In the description of this application, it should be understood that the terms "center", "longitudinal", "lateral", "length", "width", "thickness", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", "clockwise", "counterclockwise", "axial", "radial", "circumferential", etc., indicating the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings, are only for the convenience of describing this application and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation, and therefore should not be construed as a limitation of this application.

[0115] Furthermore, the terms "first," "second," etc., are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number, specific location, or specific order of the indicated technical features. Therefore, a feature defined with "first," "second," etc., may explicitly or implicitly include at least one of those features.

[0116] In the description of this application, "multiple" means at least two, such as two, three, etc., unless otherwise expressly and specifically limited.

[0117] In this application, unless otherwise expressly specified and limited, the terms "installation," "connection," "joining," "fixing," etc., should be interpreted broadly. For example, "connection" can be a fixed connection, a detachable connection, or an integral part; it can be a mechanical connection or an electrical connection; it can be a direct connection or an indirect connection through an intermediate medium; it can be the internal communication of two components or the interaction between two components, unless otherwise expressly limited. Those skilled in the art can understand the specific meaning of the above terms in this application according to the specific circumstances.

[0118] In this application, unless otherwise expressly specified and limited, "above" or "below" the second feature can mean that the first and second features are in direct contact, or that the first and second features are in indirect contact through an intermediate medium. Furthermore, "above," "over," and "on top" of the second feature can mean that the first feature is directly above or diagonally above the second feature, or simply that the first feature is at a higher horizontal level than the second feature. "Below," "below," and "under" the second feature can mean that the first feature is directly below or diagonally below the second feature, or simply that the first feature is at a lower horizontal level than the second feature.

[0119] In the description of this specification, the references to terms such as "one embodiment," "some embodiments," "example," "specific example," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of this application. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples. Moreover, without contradiction, those skilled in the art can combine and integrate the different embodiments or examples described in this specification, as well as the features of different embodiments or examples.

[0120] Although embodiments of this application have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting this application. Those skilled in the art can make changes, modifications, substitutions and variations to the above embodiments within the scope of this application.

Claims

1. A biomolecule extraction device, characterized in that, include: The container is provided with multiple receiving holes, and a connecting channel is provided between each pair of adjacent receiving holes; Magnetic beads are used to be placed in the receiving pore to adsorb biomolecules in the solution within the receiving pore; A primary magnetic field device includes a primary magnet movably disposed on the outside of the container; A secondary magnet is placed in the receiving hole, the secondary magnet being configured to be magnetized and demagnetized by the primary magnet; The secondary magnet is magnetized by the primary magnet to attract the magnetic beads, and the movement of the primary magnet can drive the secondary magnet with the attracted magnetic beads to move into another receiving hole. After the primary magnet demagnetizes the secondary magnet, the magnetic beads are dispersed in the solution in the receiving hole. The secondary magnet is a cylindrical magnet, and the primary magnet is configured such that its magnetic poles are parallel to the wall surface it contacts during movement, so that as the primary magnet moves with the secondary magnet, the secondary magnet carries the magnetic beads and rolls along the wall surface.

2. The biomolecule extraction device according to claim 1, characterized in that, The primary magnet is configured to make line contact or surface contact with the wall surface it comes into contact with during the movement of the secondary magnet.

3. The biomolecule extraction device according to claim 1, characterized in that, The container includes a container body and a container lid covering the container body. The container body is provided with a plurality of the receiving holes, and the container lid is configured to cover the plurality of the receiving holes.

4. The biomolecule extraction device according to claim 3, characterized in that, A partition wall is provided between two adjacent receiving holes, and the container cover includes a cover plate body covering the top of the receiving hole and baffles provided on the inner side of the cover plate body and respectively corresponding to the partition wall; The container lid is configured to have a first position and a second position when it is placed on the container body. In the second position, a gap is formed between the baffle and the corresponding partition wall, and the gap forms a connecting channel between the two receiving holes. In the first position, the baffle moves down to the partition wall and closes the connecting channel.

5. The biomolecule extraction device according to any one of claims 1-4, characterized in that, The primary magnet includes a permanent magnet and an electromagnet. The permanent magnet and the electromagnet are configured with parallel magnetic poles. By controlling the direction of the current, the magnetic poles of the electromagnet can be made to be opposite to or in the same direction as the magnetic poles of the permanent magnet.

6. The biomolecule extraction device according to any one of claims 1-4, characterized in that, The primary magnetic field device further includes a mounting frame, a vertically movable slider, and a horizontally movable slider, with the primary magnet mounted on the vertically movable slider; wherein, the horizontally movable slider is configured to move horizontally relative to the mounting frame, and the vertically movable slider is configured to slide vertically relative to the horizontally movable slider; A rotation drive mechanism is also provided between the up-and-down moving slider and the primary magnet, and the rotation drive mechanism is configured to drive the primary magnet to rotate relative to the up-and-down moving slider.

7. A method for extracting biomolecules, characterized in that, The method includes: The magnetic beads and the solution containing biomolecules are placed in the first receiving hole of the container, so that the biomolecules bind to the magnetic beads. A primary magnet is used to magnetize a secondary magnet located within a first receiving hole, causing the secondary magnet to attract a magnetic bead; wherein the primary magnet is located outside the first receiving hole. Move the primary magnet so that the secondary magnet, carrying the magnetic bead, moves along the container wall into the second receiving hole of the container; The secondary magnet is demagnetized, causing the magnetic beads on the secondary magnet to disperse in the solution in the second receiving hole; A primary magnet is used to magnetize a secondary magnet located in the second receiving hole, so that the secondary magnet attracts the magnetic bead. Move the primary magnet so that the secondary magnet, carrying the magnetic bead, moves along the container wall into the third receiving hole of the container; The secondary magnet is demagnetized, causing the magnetic beads on the secondary magnet to disperse in the solution in the third receiving hole; During the movement of the primary magnet carrying the secondary magnet, the primary magnet rests against the container wall with its magnetic poles parallel to the container wall; the secondary magnet is cylindrical, and during the movement of the primary magnet carrying the secondary magnet, the secondary magnet carries the magnetic bead and rolls along the container wall.

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