CN120737940B - Biomolecule extraction apparatus and method - Google Patents
Biomolecule extraction apparatus and methodInfo
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- CN120737940B CN120737940B CN202511248290.6A CN202511248290A CN120737940B CN 120737940 B CN120737940 B CN 120737940B CN 202511248290 A CN202511248290 A CN 202511248290A CN 120737940 B CN120737940 B CN 120737940B
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- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
- C12N15/1003—Extracting or separating nucleic acids from biological samples, e.g. pure separation or isolation methods; Conditions, buffers or apparatuses therefor
- C12N15/1006—Extracting or separating nucleic acids from biological samples, e.g. pure separation or isolation methods; Conditions, buffers or apparatuses therefor by means of a solid support carrier, e.g. particles, polymers
- C12N15/1013—Extracting or separating nucleic acids from biological samples, e.g. pure separation or isolation methods; Conditions, buffers or apparatuses therefor by means of a solid support carrier, e.g. particles, polymers by using magnetic beads
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Abstract
The application provides biomolecule extraction equipment and a biomolecule extraction method, wherein the biomolecule extraction equipment comprises a container provided with a plurality of containing holes, magnetic beads arranged in the containing holes, a primary magnetic field device comprising a primary magnet arranged outside the container, a secondary magnet arranged in the containing holes, wherein the secondary magnet can be magnetized and demagnetized by the primary magnet, the secondary magnet is magnetized by the primary magnet and can attract the magnetic beads, the primary magnet can drive the secondary magnet attracted with the magnetic beads to move into another containing hole, the magnetic beads are dispersed in a solution in the containing holes after the primary magnet demagnetizes the secondary magnet, the secondary magnet is a cylindrical magnet, the magnetic pole direction of the primary magnet is parallel to the contacted wall surface in the moving process, and the secondary magnet rolls along the wall surface along with the magnetic beads in the moving process of the primary magnet. The scheme provided by the application can solve the problems of the prior art that additional consumable materials are needed, samples are easy to pollute and the like in the biomolecule extraction method.
Description
Technical Field
The present disclosure relates to the field of biomolecule extraction technology, and more particularly, to a biomolecule extraction apparatus and method.
Background
One of the purification or extraction methods of biomolecules is to use nano magnetic beads as a carrier, and separate the biomolecules attached to the surfaces of the magnetic beads from impurities in the original sample under the action of a magnetic field. For example, the most common method employed in magnetic nucleic acid purification techniques is the use of silica coated magnetic beads, wherein the nucleic acid is bound to the beads in a high salt solution, the beads are collected by application of a magnetic field, the nucleic acid is thereby separated from other cellular components or sample impurities, and the purified nucleic acid is finally eluted using a low salt buffer.
Currently, there are two specific ways of biomolecule purification or extraction:
1. the magnetic beads are attracted to the inner wall of the container by a magnet arranged outside the container, then the liquid in the container is replaced by a liquid transfer device, the solution with pollutants is removed, and the steps are repeated, so that the magnetic beads can be cleaned and the nucleic acid can be eluted from the magnetic beads.
2. The magnetic beads are attracted by a magnetic rod which is arranged inside the container and is directly connected with an external machine, then the magnetic rod is moved to move the magnetic beads from one container to another container, so that the magnetic beads are separated from a solution with pollutants, and the steps are repeated, thereby realizing the cleaning of the magnetic beads and the elution of nucleic acid from the magnetic beads.
However, the currently used way of biomolecule extraction has the drawback that additional consumables are required for transporting the magnetic beads (magnetic stick sheath) or transporting the liquid (pipette tip), and in addition, mechanical arms are required for moving the magnetic stick or handling the liquid, i.e. peripheral devices (magnetic stick, pipette tip, etc.) need to enter the dissolver, which risks the cumbersome instrument structure and contamination of the sample.
Disclosure of Invention
The embodiment of the application provides a biomolecule extraction device and a biomolecule extraction method, which are used for solving the defects in the existing biomolecule extraction method.
An embodiment of the present application provides a biomolecule extraction apparatus, comprising:
the container is provided with a plurality of containing holes, and a communication channel is arranged between every two adjacent containing holes;
a magnetic bead for being placed in the accommodating hole to adsorb biomolecules in the solution in the accommodating hole;
A primary magnetic field device including a primary magnet movably disposed outside the container;
A secondary magnet disposed in the accommodation hole, the secondary magnet being configured to be magnetized and demagnetized by the primary magnet;
The secondary magnet is a cylindrical magnet, the magnetic pole direction of the primary magnet is parallel to the contacted wall surface in the moving process, so that the primary magnet drives the secondary magnet to move into the other accommodating hole, and the secondary magnet drives the magnetic beads to roll along the wall surface in the moving process of the secondary magnet.
In one embodiment, the primary magnet is arranged to be in line or surface contact with the wall surface in contact with the secondary magnet during movement of the secondary magnet.
In one embodiment, the container comprises a container body and a container cover covering the container body, wherein the container body is provided with a plurality of containing holes, and the container cover is arranged to cover the plurality of containing holes.
In one embodiment, a partition wall is arranged between two adjacent containing holes, and the container cover comprises a cover plate main body covering the top of each containing hole and baffle plates arranged on the inner side of the cover plate main body and respectively corresponding to the partition walls;
the container cover is arranged to cover the container body and has a first position and a second position, a space is formed between the baffle plate and the corresponding partition wall, the space forms a communication channel between the two containing holes, and the baffle plate moves downwards to the partition wall to close the communication channel in the first position.
In one embodiment, the primary magnet comprises a permanent magnet and an electromagnet, the magnetic pole directions of the permanent magnet and the electromagnet are arranged in parallel, and the magnetic pole of the electromagnet can be opposite to the magnetic pole of the permanent magnet or same to the magnetic pole of the permanent magnet by controlling the direction of the current.
In one embodiment, the primary magnetic field device further comprises a mounting frame, an up-and-down moving slide block and a horizontal moving slide block, wherein the primary magnet is mounted on the up-and-down moving slide block, the horizontal moving slide block is arranged to be capable of horizontally moving relative to the mounting frame, and the up-and-down moving slide block is arranged to be capable of vertically sliding relative to the horizontal moving slide block;
and a rotary driving mechanism is arranged between the up-and-down moving slide block and the primary magnet, and the rotary driving mechanism is arranged to drive the primary magnet to rotate relative to the up-and-down moving slide block.
The embodiment of the application also provides a biomolecule extraction method, which comprises the following steps:
placing the magnetic beads and a solution containing the biomolecules in a first receiving well of a container such that the biomolecules bind to the magnetic beads;
Magnetizing a secondary magnet positioned in the first accommodating hole by using a primary magnet so that the secondary magnet attracts magnetic beads, wherein the primary magnet is positioned outside the first accommodating hole;
moving the primary magnet such that the secondary magnet moves with the magnetic beads along the container wall into the second receiving aperture of the container;
demagnetizing the secondary magnet so that the magnetic beads on the secondary magnet are dispersed in the solution of the second accommodating hole;
Magnetizing a secondary magnet positioned in the second accommodating hole by using a primary magnet, so that the secondary magnet attracts the magnetic beads;
Moving the primary magnet such that the secondary magnet moves with the magnetic beads along the container wall into the third receiving aperture of the container;
Demagnetizing the secondary magnet so that the magnetic beads on the secondary magnet are dispersed in the solution of the third accommodating hole;
The primary magnet is abutted against the container wall and the magnetic pole direction is parallel to the container wall in the moving process of the primary magnet carrying the secondary magnet; the secondary magnet is cylindrical, and the primary magnet rolls along the container wall along with the magnetic beads in the moving process of the secondary magnet.
The biomolecule extraction device provided by the embodiment of the application adopts a mode of driving the secondary magnet in the container to move by the primary magnet to transfer the magnetic beads adsorbed with biomolecules, and can solve the problems of increased cost and easiness in sample pollution caused by additional consumable materials in the mode of replacing liquid in the container by a pipette or conveying the magnetic beads by a magnetic rod in the prior art.
Additional features and advantages of the application will be set forth in the description which follows, and in part will be obvious from the description, or may be learned by practice of the application. Other advantages of the application may be realized and attained by the structure particularly pointed out in the written description and drawings.
Drawings
The accompanying drawings are included to provide an understanding of the principles of the application, and are incorporated in and constitute a part of this specification, illustrate embodiments of the application and together with the description serve to explain, without limitation, the principles of the application.
FIG. 1 is a schematic structural view 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;
FIG. 2 is a schematic view of the structure of the biomolecule extraction device in FIG. 1, taken at a first receiving aperture;
fig. 3 is a schematic structural view of a biomolecule extraction device in one embodiment of the present application, wherein magnetic beads in a first receiving hole are attracted by a secondary magnet;
FIG. 4 is a schematic view of the structure of the biomolecule extraction device in FIG. 3, taken at a first receiving hole;
Fig. 5 is a schematic structural view of a biomolecule extraction device in 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;
FIG. 6 is a schematic view of the structure of the biomolecule extraction device in FIG. 5 cut at a second receiving hole;
FIG. 7 is a schematic diagram of a structure in which a secondary magnet attracted with magnetic beads is attracted to a container wall by a primary magnet (the magnetic pole direction of the primary magnet is parallel to the medium surface) according to one embodiment of the present application;
FIG. 8 is a schematic diagram of a structure in which a secondary magnet attracted with magnetic beads is attracted to a container wall by a primary magnet (the magnetic pole direction of the primary magnet is perpendicular to the medium surface) according to another embodiment of the present application;
FIG. 9 is a schematic diagram of a structure in which a primary magnet is in line contact with a medium surface and a magnetic pole direction of the primary magnet is parallel to the medium surface according to an embodiment of the present application;
FIG. 10 shows a schematic top view of the structure shown in FIG. 9;
FIG. 11 is a schematic view of a structure in which a primary magnet is in surface contact with a medium surface and the magnetic pole direction of the primary magnet is parallel to the medium surface according to an embodiment of the present application;
FIG. 12 is a schematic top view of the structure shown in FIG. 11;
FIG. 13 is a schematic view of a structure in which a primary magnet is in surface contact with a medium surface and the magnetic pole direction of the primary magnet is perpendicular to the medium surface according to an embodiment of the present application;
FIG. 14 is a schematic top view of the structure shown in FIG. 13;
FIG. 15 is a schematic diagram of the structure of a primary magnet in accordance with one embodiment of the application;
FIG. 16 is a view of the primary magnet of FIG. 15 from one side;
FIG. 17 is a view of the primary magnet of FIG. 15 from one end;
FIG. 18 is a schematic diagram of a secondary magnet in an embodiment in accordance with the application;
Fig. 19 is a schematic view showing a state in which an electromagnet in a primary magnet is in the same direction as the magnetic pole of a permanent magnet so that a secondary magnet is attracted in accordance with an embodiment of the present application;
FIG. 20 is a schematic diagram of a state in which the electromagnet in the primary magnet is reversed with the poles of the permanent magnet so that the secondary magnet is disengaged in accordance with one embodiment of the present application;
FIG. 21 is a schematic diagram of the structure of a primary magnetic field device in accordance with one embodiment of the application;
FIG. 22 is a schematic diagram of the primary magnetic field device mated with a container in accordance with one embodiment of the present application;
FIG. 23 is a schematic diagram of a primary magnetic field device in accordance with another embodiment of the application;
fig. 24 is a schematic structural view of a primary magnetic field device according to still another embodiment of the present application.
Reference numerals illustrate:
1-container, 11-container body, 111-outer side wall, 112-partition wall, 12-container cover, 121-cover plate main body, 122-baffle plate, 13-accommodation hole, 13 a-first accommodation hole, 13 b-second accommodation hole, 13 c-third accommodation hole, 14-communication channel, 2-magnetic bead, 3-primary magnetic field device, 31-primary magnet, 311-permanent magnet, 312-electromagnet, 313-magnetizer, 3131-magnetic guide plate, 3132-magnetic field focusing end, 32-motor, 33-up-down moving slide block, 34-horizontal moving slide block and 4-secondary magnet.
Detailed Description
The present application has been described in terms of several embodiments, but the description is illustrative and not restrictive, and it will be apparent to those of ordinary skill in the art that many more embodiments and implementations are possible within the scope of the described embodiments. 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 possible. Any feature or element of any embodiment may be used in combination with or in place of any other feature or element of any other embodiment unless specifically limited.
The present application includes and contemplates combinations of features and elements known to those of ordinary skill in the art. The disclosed embodiments, features and elements of the present application may also be combined with any conventional features or elements to form a unique inventive arrangement. Any feature or element of any embodiment may also be combined with features or elements from other inventive arrangements to form another unique inventive arrangement. It is therefore to be understood that any of the features shown and/or discussed in the present application may be implemented alone or in any suitable combination. Accordingly, the embodiments are not to be restricted except in light of the attached claims and their equivalents. Further, various modifications and changes may be made within the scope of the appended claims.
Furthermore, in describing representative embodiments, the specification may have presented the method and/or process as a particular sequence of steps. However, to the extent that the method or process does not rely on the particular order of steps set forth herein, the method or process should not be limited to the particular sequence of steps described. Other sequences of steps are possible as will be appreciated by those of ordinary skill in the art. Accordingly, the particular order of the steps set forth in the specification should not be construed as limitations on the claims. Furthermore, the claims directed to the method and/or process should not be limited to the performance of their steps in the order written, and one skilled in the art can readily appreciate that the sequences may be varied and still remain within the spirit and scope of the embodiments of the present application.
An embodiment of the present application provides a biomolecule extraction apparatus, as in the embodiment of fig. 1-6, comprising a container 1, magnetic beads 2, a primary magnetic field device 3 and a secondary magnet 4.
The container 1 is provided with a plurality of receiving holes 13 each having a communication passage 14 between adjacent two of the receiving holes 13, the magnetic beads 2 are disposed in the receiving holes 13 to adsorb biomolecules in a solution in the receiving holes 13, the primary magnetic field device 3 includes a primary magnet 31 movably disposed outside the container 1, and a secondary magnet 4 is disposed in the receiving holes 13, the secondary magnet 4 is disposed to be magnetized and demagnetized by the primary magnet 31, and the secondary magnet 4 may be made of a material having high magnetic permeability such as soft iron, silicon steel, or the like.
Wherein the secondary magnet 4 is magnetized by the primary magnet 31 to attract the magnetic beads 2, the primary magnet 31 can drive the secondary magnet 4 to move into the other accommodating hole 13, the magnetic beads 2 are dispersed in the solution of the accommodating hole 13 after the primary magnet 31 demagnetizes the secondary magnet 4, the secondary magnet 4 is a cylindrical magnet, the magnetic beads 2 are attracted at two ends of the secondary magnet 4, and the primary magnet 31 is arranged in such a way that the magnetic pole direction is parallel to the contacted wall surface in the moving process, so that the secondary magnet 4 rolls along the wall surface with the magnetic beads 2 in the moving process of the primary magnet 31 with the secondary magnet 4. The magnetic pole direction refers to the direction from the S pole to the N pole or the direction from the N pole to the S pole of the magnet.
Fig. 1 to 6 show that the plurality of receiving holes 13 of the container 1 include a first receiving hole 13a, a second receiving hole 13b, a third receiving hole 13c, and the like.
Fig. 1 and 2 show that the magnetic beads 2 and the solution containing the biomolecules are disposed in the first accommodation hole 13a, and the magnetic beads 2 and the biomolecules are combined to form a complex in the first accommodation hole 13 a. Wherein, the magnetic beads 2 can be superparamagnetism magnetic beads, when an external magnetic field exists, the superparamagnetism magnetic beads are magnetized and attracted to two ends of the secondary magnet 4, when no external magnetic field exists, the superparamagnetism magnetic beads are easy to be demagnetized due to thermodynamic action, hysteresis phenomenon does not exist, aggregation does not exist, the superparamagnetism magnetic beads can be scattered in a solution, and compared with the paramagnetic magnetic beads, the superparamagnetism magnetic beads are easier to be magnetized and have stronger attraction.
Biomolecule binding in the present application refers to non-covalent binding of the biomolecule to another object, such as adsorption, including physical adsorption, chemical adsorption, affinity adsorption, and the like.
Fig. 3 and 4 show a state in which the primary magnet 31 magnetizes the secondary magnet 4, the secondary magnet 4 attracts the magnetic beads 2 in the first accommodation hole 13a, the secondary magnet 4 follows upward along the container wall as the primary magnet 31 moves upward, and after rolling upward and passing through the communication passage between the first accommodation hole 13a and the second accommodation space 13b, the secondary magnet 4 enters the second accommodation hole 13b to further wash the biomolecules by the solution in the second accommodation hole 13 b.
Fig. 5 and 6 show a state in which the secondary magnet 4 is demagnetized and the magnetic beads 2 are dispersed in the solution after the secondary magnet 4 enters the second accommodation hole 13 b.
The biomolecule extraction device provided by the embodiment of the application adopts the mode that the primary magnet 31 drives the secondary magnet 4 in the container to move so as to realize the transfer of the magnetic beads 2 adsorbed with biomolecules, and can solve the problems that in the prior art, the cost is increased and samples are easy to pollute due to the fact that extra consumable materials are needed in the mode that a liquid in the container is replaced by a liquid transfer device or the magnetic beads are conveyed by a magnetic rod. In addition, as the secondary magnet 4 rolls along the wall surface with the magnetic beads 2, the moving efficiency of the secondary magnet 4 is higher, and the extraction efficiency of biological molecules can be effectively improved.
In the example shown in fig. 7, the secondary magnet 4 is a cylindrical magnet, the magnetic pole direction of the primary magnet 31 is parallel to the contacted wall surface, so that when the primary magnet 31 applies a magnetic field, the secondary magnet 4 is magnetized, the magnetic beads 2 are attracted to two ends of the secondary magnet 4, the axis of the secondary magnet 4, namely the magnetic field pole, is parallel to the wall surface, the secondary magnet 4 can roll along the wall surface in the process that the primary magnet 31 drives the secondary magnet 4 to move, and the magnetic beads 2 attracted to two ends of the secondary magnet 4 do not rub with the wall surface, so that the magnetic bead loss is small.
It will be appreciated that the secondary magnet 4 is a cylindrical magnet in order for the secondary magnet 4 to roll during movement, and in other embodiments the secondary magnet 4 is of other shapes, for example, square, the square secondary magnet 4 may be disposed to move along a wall surface with a high frictional resistance.
In the example of fig. 8, the magnetic pole direction of the primary magnet 31 is perpendicular to the wall surface of the container, when the primary magnet 31 applies a magnetic field, the magnetic beads 2 are attracted to two ends of the secondary magnet 4, and the magnetic pole direction of the secondary magnet 4 is perpendicular to the wall surface, during the process that the primary magnet 31 drives the secondary magnet 4 to move, one end surface of the secondary magnet 4 contacts the wall surface, the magnetic beads 2 on the end surface are lost during the moving process, and the secondary magnet 4 moves along the wall surface instead of rolling during the moving process, so that the problem of high moving resistance also exists.
In some examples, the secondary magnet 4 is a cylindrical magnet, the magnetic pole direction of the primary magnet 31 is parallel to the contacted wall surface, and the primary magnet 31 is arranged to be in line contact or surface contact with the contacted wall surface during the process of driving the secondary magnet 4 to move.
As in the examples of fig. 9 and 10, the magnetic pole direction of the primary magnet 31 is parallel to the contacted wall surface, and the primary magnet 31 is in line contact with the contacted wall surface. In this way, when the magnetized secondary magnet 4 is attracted on the wall surface, the axial direction (namely, the polar direction of the induced secondary magnetic field) is parallel to the contacted wall surface, so that the secondary magnet 4 can roll along the wall surface, the primary magnet 31 is in line contact with the contacted wall surface, magnetic force lines are concentrated, the guiding force on the secondary magnet 4 is larger, the rolling effect of the secondary magnet 4 under the driving of the primary magnet 31 is good, the moving efficiency is high, and the loss of the magnetic beads 2 is smaller.
In the examples of fig. 11 and 12, the magnetic pole direction of the primary magnet 31 is parallel to the contacted wall surface, and the primary magnet 31 is in surface contact with the contacted wall surface. The primary magnet 31 is in line contact with the wall surface in contact with the wall surface, and the secondary magnet 4 jumps during movement, which is not as stable as the line contact.
In the examples of fig. 13 and 14, the magnetic pole direction of the primary magnet 31 is perpendicular to the contacted wall surface, so that the axis (i.e., the magnetic field pole direction) of the secondary magnet 4 is perpendicular to the contacted wall surface when attracted thereto, whereby the magnetic beads 2 on the end of the secondary magnet 4 near the wall surface are dropped off during movement, and the movement resistance of the secondary magnet 4 is large.
In one embodiment, the container 1 includes a container body 11 and a container cover 12 covering the container body 11, the container body 11 is provided with a plurality of receiving holes 13, and the container cover 12 is provided to cover the plurality of receiving holes 13. By providing the container cover 12, the problem that the container is not closed, the magnetic beads 2 are exposed, and aerosol is easily generated or is contacted with aerosol of other samples in the prior art can be solved.
In an example, referring to fig. 1 to 6, the container body 11 includes an outer sidewall 111 and a partition wall 112 provided between adjacent two of the receiving holes 13, and the container cover 12 is provided to include a cover plate body 121 covering the top of the receiving holes 13 and baffle plates 122 provided inside the cover plate body 121 and respectively corresponding to the partition walls 112.
The container cover 12 is provided to have a first position and a second position when it is attached to the container body 11, the first position being below the second position. Wherein in the second position, a space is formed between the shutter 122 and the corresponding partition wall 112, the space forming the communication passage 14 between the two accommodation holes 13, and in the first position, the shutter 122 moves down to the partition wall 112 to close the communication passage 14.
Since each of the accommodating holes 13 has a different reagent, respectively, it is not mixed, and it is necessary that the communication passage 14 between the accommodating holes is closed during transportation. In the extraction of biomolecules, the beads 2 are transferred from one well to another with the biomolecules for various purposes, such as binding to biomolecules, removing impurities, releasing biomolecules, etc., and closing the communication channel 14 prevents mixing of the different Kong Zhongshi agents so as not to affect the purity of the final biomolecules.
In some embodiments, the primary magnet 31 may employ a permanent magnet or an electromagnet.
In another embodiment, as shown in fig. 15 to 17, the primary magnet 31 includes a permanent magnet 311 and an electromagnet 312, the permanent magnet 311 and the electromagnet 312 are arranged with magnetic poles in parallel, and the magnetic poles of the electromagnet 312 can be made opposite to the magnetic poles of the permanent magnet 311 or the same direction as the magnetic poles of the permanent magnet 311 by controlling the direction of the current.
The primary magnet 31 controls the magnetic field intensity by controlling the current of the electromagnet 312, so that the magnetization and demagnetization of the secondary magnet 4 can be conveniently realized, when the magnetic poles of the electromagnet 312 and the permanent magnet 311 are opposite, the magnetic fields generated by the two are mutually offset, so that the magnetic field generated by the primary magnet 31 is very weak or no, and when the magnetic poles of the electromagnet 312 and the permanent magnet 311 are in the same direction, the magnetic fields generated by the two are superposed, so that the primary magnet 31 generates a stronger magnetic field. In addition, the magnetic field strength of the electromagnet 312 can also be changed by controlling the current strength of the electromagnet 312, for example, when the electromagnet 312 is not current, the magnetic field generated by the primary magnet 31 is weakened.
In the process of demagnetizing the secondary magnet 4 to disperse the magnetic beads 2 in the solution, the magnetic field intensity of the primary magnet 31 is controlled to make the secondary magnet 4 rapidly and repeatedly attract and separate from the primary magnet 31, so that turbulence can be caused in the liquid phase, and the mixing of the liquid phase components and the dispersion of the magnetic beads 2 are facilitated.
The primary magnet 31 may further include a magnetizer 313, an electromagnet 312 and a permanent magnet 311 being fixed to the magnetizer 313, one end of the magnetizer 313 being formed as a magnetic field focusing end 3132 for magnetizing the secondary magnet 4. The magnetic conductor 313 may be made of a material with high magnetic permeability, such as soft iron, silicon steel, etc., where the magnetic permeability of the magnetic conductor 313 is far higher than that of the surrounding air, etc., and the magnetic lines of force will preferentially propagate along the path of the magnetic conductor 313, so as to change the original propagation direction of the magnetic lines of force, so that by setting a suitable material, shape and size of the magnetic conductor 313, the magnetic flux density of the primary magnet 31 can be increased at the magnetic field focusing end 3132 to achieve an increase in the magnetic field strength near the primary magnet, i.e. focusing, so that the secondary magnet 4 can be effectively magnetized.
As shown in the example of fig. 15 to 17, the magnetic conductor 313 includes two magnetic conductive plates 3131 arranged in parallel, the electromagnet 312 and the permanent magnet 311 are fixed between the two magnetic conductive plates 3131, and the magnetic pole directions of the electromagnet 312 and the permanent magnet 311 are each set from one magnetic conductive plate 3131 toward the other magnetic conductive plate 3131, and one ends of the two magnetic conductive plates 3131 form a magnetic field focusing end 3132. Thus, the magnetic field generated by the magnetic field focusing end 3132 is directed from one magnetic conductive plate 3131 toward the other magnetic conductive plate 3131, and when the magnetic field focusing end 3132 abuts against a medium surface (e.g., a container wall of the container 1), the magnetic pole direction of the magnetic field focusing end 3132 may be parallel to the abutted medium surface. As shown in fig. 19 and 20, the magnetic pole direction of the secondary magnet 4 magnetized by the primary magnet 31 is parallel to the medium surface, the magnetic beads 2 can be gathered at two ends of the magnetic pole of the secondary magnet 4, when the secondary magnet 4 adopts a cylindrical structure, the primary magnet 31 can drive the secondary magnet 4 to roll along the medium surface, the friction between the secondary magnet 4 and the attracted magnetic beads 2 and the medium surface is small, the magnetic bead loss is small, and the moving efficiency is high. Wherein fig. 19 shows a state in which the magnetic force of the primary magnet 31 intensifies magnetization of the secondary magnet 4 so that the secondary magnet 4 moves toward the primary magnet 31 to be attracted to the medium surface, fig. 20 shows a state in which the magnetic force of the primary magnet 31 is canceled so that the secondary magnet 4 demagnetizes to be separated from the movement of the primary magnet 31,
In one example, the magnetic field focusing end 3132 is configured to taper in cross-section in a direction toward the tip. Because the magnetic flux density is larger when the same magnetic flux and the sectional area are smaller, the magnetic flux density is larger at the magnetic field focusing end 3132 by arranging the cross section of the magnetic field focusing end 3132 to be gradually reduced, and the corresponding magnetic field is stronger.
As in the examples in fig. 16 and 17, both side surfaces of each magnetic conductive plate 3131 are inclined toward each other in a direction toward the tip so that the cross section is tapered, and both side surfaces of each magnetic conductive plate 3131 are inclined toward each other in a direction toward between the two magnetic conductive plates 3131 so that the tip 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. I.e., the end surface area of the two magnetic conductive plates 3131 near the middle position is smaller, so that the magnetic force lines are concentrated toward the middle position.
In the examples of fig. 16 and 17, the gap width a between the two magnetic conductive plates 3131 is less than 3L, preferably a=l, and the minimum width C of the two trapezoidal end faces of the magnetic field focusing end 3132 is less than 3D. Where 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 the secondary magnet 4 shown in fig. 18, wherein both ends of the secondary magnet 4 are planar or hemispherical.
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.
Wherein the stronger the magnetic field of the primary magnet 31, the stronger the induced secondary magnetic field, when the primary magnet 31 has stronger magnetic field, the secondary magnet 4 is attracted to the position nearest to the primary magnet 31 first, and the secondary magnet 4 is further magnetized, and the induced secondary magnetic field attracts the magnetic beads 2 in the solution to both ends of the secondary magnet 4, namely, both poles of the secondary magnetic field.
Under the action of the strong primary magnetic field, the speed at which the primary magnet 31 attracts the secondary magnets 4 to approach each other or the speed at which the secondary magnets 4 separate from the primary magnet 31 due to gravity in the absence of the primary magnetic field is faster than the speed at which the secondary magnets 4 attract the magnetic beads 2 to both ends of the secondary magnets 4. After the secondary magnet 4 is attracted to the focused strong magnetic field of the primary magnet 31, the induced secondary magnetic field attracts the magnetic beads 2 in the solution to attract the magnetic beads 2 to both ends of the secondary magnet 4.
In one embodiment, as shown in fig. 21 to 24, the primary magnetic field device 3 further includes a mounting frame, an up-and-down moving slider 33, and a horizontal moving slider 34, wherein the primary magnet 31 is mounted on the up-and-down moving slider 33, and wherein the horizontal moving slider 34 is configured to be horizontally movable with respect to the mounting frame, and the up-and-down moving slider 33 is configured to be vertically slidable with respect to the horizontal moving slider 34.
The primary magnetic field device 3 provided by the application can drive the primary magnet 31 to move up and down and horizontally, so that the primary magnet 31 can move through the primary magnetic field device 3, and the automation of the movement of the secondary magnet 4 can be realized in the process of extracting biomolecules.
In one embodiment, a rotation driving mechanism is provided between the primary magnet 31 and the up-down moving slider 33, and the rotation driving mechanism is configured to be capable of driving the primary magnet 31 to rotate. The rotation driving mechanism may be a motor 32, and the motor 32 drives the primary magnet 31 to rotate. By the rotation of the primary magnet 31, the secondary magnet 4 can be driven in a rotation direction, thereby making it more suitable for movement in a predetermined movement direction.
In one embodiment, one or more primary magnets 31 may be disposed on the up-and-down moving slider 33, and a rotation mechanism may be disposed between each primary magnet 31 and the up-and-down moving slider 33, respectively.
Fig. 21 and 22 show a state in which one primary magnet 31 is provided on the up-and-down moving slider 33 of the primary magnetic field device 3, wherein fig. 22 shows a state in which the primary magnet 31 abuts on the outer side wall of the container 1 having a plurality of receiving holes.
Fig. 23 and 24 show that four primary magnets 31 are provided on the up-and-down moving slider 33, wherein fig. 23 shows that four motors 32 are arranged in an array on the up-and-down moving slider 33, each motor being connected to one primary magnet 31, respectively. Fig. 24 shows that two motors 32 are respectively provided on the up-and-down moving slider 33, and both end portions of each motor 32 are connected to the primary magnet 31. Of course, other numbers of primary magnets 31 may be provided for moving the slider 33 up and down, and a plurality of primary magnets 31 may be provided for each primary magnetic field device 3, so that the steps of extracting biomolecules from a plurality of samples may be performed simultaneously.
The embodiment of the application also provides a biomolecule extraction method, which comprises the following steps:
Placing the magnetic beads 2 and the solution containing the biomolecules in the first accommodation hole 13a of the container 1 so that the biomolecules are bound to the magnetic beads 2;
Magnetizing the secondary magnet 4 positioned in the first accommodation hole 13a by using the primary magnet 31 so that the secondary magnet 4 attracts the magnetic beads 2, wherein the primary magnet 31 is positioned outside the first accommodation hole 13 a;
Moving the primary magnet 31 so that the secondary magnet 4 moves with the magnetic beads 2 along the container wall into the second accommodation hole 13b of the container 1, the solution containing impurities remains in the first accommodation hole 13 a;
Demagnetizing the secondary magnet 4 so that the magnetic beads 2 on the secondary magnet 4 are dispersed in the solution of the second accommodation hole 13b, so that the magnetic beads 2 are in full contact with the solution in the second accommodation hole 13b, and the biomolecules on the magnetic beads 2 are dispersed in the solution to perform a second washing of the biomolecules;
Magnetizing the secondary magnet 4 positioned in the second accommodation hole 13b with the primary magnet 31 so that the secondary magnet 4 attracts the magnetic beads 2;
moving the primary magnet 31 such that the secondary magnet 4 moves with the magnetic beads 2 along the container wall into the third accommodation hole 13c of the container 1;
The secondary magnet 4 is demagnetized so that the magnetic beads 2 on the secondary magnet 4 are dispersed in the solution of the third accommodation hole 13c to further elute the biomolecules.
Of course, the magnetic beads 2 adsorbed with the biomolecules may be further transferred into the fourth accommodation hole by the secondary magnet 4.
In some embodiments, the primary magnet 31 is held against the container wall with the magnetic poles parallel to the container wall during the movement of the primary magnet 31 with the secondary magnet 4.
Wherein the secondary magnet 4 is cylindrical, and the primary magnet 31 rolls along the container wall with the magnetic beads 2 during the movement of the secondary magnet 4.
The biomolecule extraction method provided by the application can be carried out by adopting the biomolecule extraction equipment provided by the application.
In the description of the present 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, etc., organic molecules derived from or associated with or acting on an organism.
In the present application, the terms attraction, adsorption, and bonding are interchangeable, and the specific terms are intended to be dependent on the context, in general attraction may be an interaction before or after two objects come into physical contact, adsorption and bonding being an action or effect after physical contact. Adsorption biomolecules may include physical adsorption, chemical adsorption, affinity adsorption, and the like.
In the description of the present 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. indicate orientations or positional relationships based on the orientations or positional relationships shown in the drawings are merely for convenience in describing the present application and simplifying the description, and do not indicate or imply that the device or element being referred to must have a specific orientation, be configured and operated in a specific orientation, and therefore should not be construed as limiting the present application.
Furthermore, the terms "first," "second," and the like, herein, are used for descriptive purposes only and are not to be construed as indicating or implying a relative importance or implying a particular order or number of features in which such is indicated. Thus, a feature defining "first," "second," etc. can include at least one such feature, either explicitly or implicitly.
In the description of the present application, the meaning of "plurality" means at least two, for example, two, three, etc., unless specifically defined otherwise.
In the present application, unless explicitly specified and limited otherwise, the terms "mounted," "connected," "secured," and the like are to be construed broadly, and for example, "connected" may be either permanently connected or removably connected or integrally formed, mechanically connected or electrically connected, directly connected or indirectly connected via an intervening medium, or may be in communication between two elements or in an interaction relationship between two elements, unless otherwise explicitly specified. The specific meaning of the above terms in the present application can be understood by those of ordinary skill in the art according to the specific circumstances.
In the present application, unless expressly stated or limited otherwise, a first feature "up" or "down" a second feature may be the direct contact of the first and second features, or the indirect contact of the first and second features through an intervening medium. Moreover, a first feature being "above," "over" and "on" a second feature may be a first feature being directly above or obliquely above the second feature, or simply indicating that the first feature is level higher than the second feature. The first feature being "under", "below" and "beneath" the second feature may be the first feature being directly under or obliquely below the second feature, or simply indicating that the first feature is less level than the second feature.
In the description of the present specification, a description referring to terms "one embodiment," "some embodiments," "examples," "specific examples," or "some examples," etc., means that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the present application. In this specification, schematic representations of the above terms are not necessarily directed to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples. Furthermore, the different embodiments or examples described in this specification and the features of the different embodiments or examples may be combined and combined by those skilled in the art without contradiction.
While embodiments of the present application have been shown and described above, it will be understood that the above embodiments are illustrative and not to be construed as limiting the application, and that variations, modifications, alternatives and variations may be made to the above embodiments by one of ordinary skill in the art within the scope of the application.
Claims (7)
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| CN219079544U (en) * | 2022-12-20 | 2023-05-26 | 融智生物科技（青岛）有限公司 | Magnetic plate and magnetic frame |
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| JP4039297B2 (en) * | 2003-04-08 | 2008-01-30 | 横河電機株式会社 | Extraction method and extraction device for biopolymer fixed to magnetic beads |
| EP2027922A1 (en) * | 2007-08-02 | 2009-02-25 | Qiagen GmbH | Method and device for securing/stabilising a sample |
| JP2010042367A (en) * | 2008-08-14 | 2010-02-25 | National Institute Of Advanced Industrial & Technology | High-gradient magnetic separator equipped with demagnetization circuit |
| KR20120116777A (en) * | 2011-04-13 | 2012-10-23 | 삼성테크윈 주식회사 | Container for extracting bio material and method for extracting bio material therewith |
| CN104531526B (en) * | 2015-01-14 | 2016-08-24 | 湖南圣维基因科技有限公司 | A kind of paramagnetic particle method nucleic acid-extracting apparatus |
| CN106148184B (en) * | 2015-04-09 | 2018-08-31 | 奥然生物科技（上海）有限公司 | A kind of reagent cartridge being provided with magnetic bead transfer organization |
| ES2975426T3 (en) * | 2019-03-15 | 2024-07-05 | Siemens Healthcare Diagnostics Inc | Method and apparatus for manipulating magnetic beads |
| EP3922991A1 (en) * | 2020-06-10 | 2021-12-15 | PreOmics GmbH | Dispersion using a moving magnet |
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| CN110139713A (en) * | 2015-09-02 | 2019-08-16 | 泰肯贸易股份公司 | Liquid bead separation in microfluidics |
| CN219079544U (en) * | 2022-12-20 | 2023-05-26 | 融智生物科技（青岛）有限公司 | Magnetic plate and magnetic frame |
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