Specific cell enrichment and magnetic separation system based on immunomagnetic beads

Abstract

The invention relates to the technical field of cell enrichment and separation equipment, in particular to a specific cell enrichment and magnetic separation system based on immunomagnetic beads. In order to solve the problem that an existing classifier is inconvenient to use, the following technical scheme is provided: a shelving module is mounted on the outer wall of the classifier, a sorting column is placed on a shelving groove of the shelving module, and an auxiliary unit and an adjusting unit mounted in the classifier are mounted in the shelving module; a moving block is installed on the outer wall of the sealing block, a pull rope is installed on the outer wall of the moving block, a sliding block is installed at the other end of the pull rope, and a rotating plate is movably connected to the inner wall of the placing module through a pin shaft. The placement state of the permanent magnet when the permanent magnet is not used and in use is changed, so that magnetic dust particles cannot be adsorbed on the placement module; and after being installed, the separation column can move upwards to adjust the liquid dropping speed, so that the operation difficulty of magnetic separation is reduced.

Description

Technical Field

[0001] The present invention relates to the technical field of cell enrichment and sorting equipment, and particularly relates to a specific cell enrichment and magnetic sorting system based on immunomagnetic beads. Background Art

[0002] Specific cell enrichment and magnetic sorting is a commonly used technique in biomedical research for separating specific types of cells from a mixed cell population. This technique mainly relies on the action of magnetic microparticles (magnetic beads) and magnetic fields. By attaching specific antibodies or ligands to the magnetic beads, they can specifically bind to target cells, thereby achieving the separation and enrichment of target cells.

[0003] When the existing sorter is in use, the enriched liquid is usually magnetically sorted on the sorting column by the way of dropping liquid. The dropping speed needs to be controlled slowly to ensure that the dropping liquid can be fully adsorbed and sorted by the magnetic field in the sorting column. The above operations require the staff to repeatedly perform the dropping operation with a special dropper. When magnetically sorting a large-capacity enriched liquid, the work intensity of the staff is high, and it is difficult to always ensure the correct dropping speed, resulting in fluctuations in the actual magnetic sorting mis-screening rate. In addition, the permanent magnets of the existing sorter are fixed near both sides of the sorting column and cannot be adjusted. When not in use, magnetic dust and debris are easily accumulated on the wall near the permanent magnet, affecting the magnetic field strength and direction, and increasing the actual magnetic sorting mis-screening rate of the sorter. Summary of the Invention

[0004] The purpose of this part is to outline some aspects of the embodiments of the present invention and briefly introduce some preferred embodiments. Simplifications or omissions may be made in this part, as well as in the abstract and title of the present application, to avoid obscuring the purpose of this part, the abstract, and the title. However, such simplifications or omissions shall not be used to limit the scope of the present invention.

[0005] Aiming at the above-mentioned drawbacks of the existing technology, the present invention provides a theme of a specific cell enrichment and magnetic sorting system based on immunomagnetic beads, which can effectively solve the problem of unstable magnetic sorting mis-screening rate in the existing technology.

[0006] To achieve the above object, the present invention is realized through the following technical solutions: The present invention provides a specific cell enrichment and magnetic sorting system based on immunomagnetic beads, including: a sorter, a shelving module, and a sorting column. Among them, the shelving module is installed on the outer wall of the sorter, the sorting column is placed on the shelving groove of the shelving module, an auxiliary unit is installed inside the shelving module, and an adjustment unit is installed inside the sorter. The auxiliary unit includes a closing block installed on the inner wall of the shelf slot of the shelf module, a moving block is installed on the outer wall of the closing block, a pull rope is installed on the outer wall of the moving block, a slider is installed on the other end of the pull rope, the inner wall of the shelf module is movably connected to a rotating plate through a pin shaft, and a sliding groove is opened on the inner wall of the shelf module.

[0007] Furthermore, a card slot is provided on the top of the closing block, a card block is installed on the inner wall of the shelf module, a toggle rod is installed on the top of the card block, and the top end of the toggle rod extends out of the top of the shelf module.

[0008] Furthermore, a permanent magnet is installed on the outer wall of the rotating plate, and two groups of rubber pads are installed on the outer wall of the rotating plate, and the two groups of rubber pads are respectively located on the upper and lower sides of the permanent magnet, and when the rotating plate rotates, the permanent magnet and the rubber pad are embedded in the slide groove, and the rubber pad slightly protrudes in the shelf groove of the shelf module, and a return spring is installed on the outer wall on the other side of the rotating plate, and the other end of the return spring is connected to the inner wall of the shelf module.

[0009] Furthermore, a support plate is installed on the top of the separator, an enrichment column is installed on the top of the support plate, and the enrichment column is located directly above the shelving module.

[0010] Furthermore, the adjustment unit comprises a push column installed on the outer wall of the closing block, the inner wall of the push column is connected with an L-shaped rod, one end of the L-shaped rod is installed with a pulling spring, and the inner wall of the enrichment column is installed with a closing plate.

[0011] Furthermore, a vertical rod is installed on the top of the L-shaped rod, a mounting spring connected to the top of the L-shaped rod is installed on the bottom of the vertical rod, a friction pad is installed on the other end of the L-shaped rod, and a resistance piece is installed on the top of the L-shaped plate.

[0012] Furthermore, a compression spring is installed on the inner top wall of the closing plate, a horizontal plate is installed at the bottom of the compression spring, a pull rod is installed at the bottom of the horizontal plate, a conical plug is installed at the bottom of the pull rod, and a sealing gasket is installed on the inner bottom wall of the enrichment column.

[0013] Furthermore, the pressing spring applies downward pressure to the transverse plate, the conical plug is sealed against the sealing gasket, and a pressing opening is provided at the bottom of the closing plate.

[0014] Furthermore, one end of the L-shaped rod is located at the bottom side of the closing plate, and the other end of the L-shaped rod movably extends to the interior of the closing block. Beneficial Effects

[0015] Compared with the known prior art, the technical solution provided by the present invention has the following beneficial effects: 1. By changing the placement state of the permanent magnet when it is not in use and when it is in use, magnetic dust particles will not be adsorbed on the shelving module, ensuring that the magnetic field strength and direction remain constant during each magnetic separation, effectively reducing the false screening rate of magnetic separation; 2. It can be firmly clamped during the installation of the separation column, so that the separation column will not shake during dripping, and the separation column always remains on the same side of the permanent magnet, improving the effect of magnetic separation; 3. When the separation column can be located directly below the enrichment column after installation, the bottom of the enrichment column automatically starts to drip at a uniform speed, and the position of the separation column can be moved to adjust the dripping speed, improving the defects of high labor intensity of manual dripping and fluctuating manual dripping speed. Description of the Drawings

[0016] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required for the description of the embodiments or the prior art. Obviously, the drawings in the following description are only some embodiments of the present invention, and those of ordinary skill in the art can also obtain other drawings based on these drawings without creative work.

[0017] Figure 1 It is the overall schematic diagram of the present invention; Figure 2 It is Figure 1 the enlarged schematic diagram of the structure at A in Figure 3 It is the schematic diagram of the shelving module of the present invention; Figure 4 It is Figure 3 the enlarged schematic diagram of the structure at B in

[0018] Figure 5 It is the schematic diagram of the auxiliary unit of the present invention.

[0019] Figure 6 It is the schematic diagram of the adjustment unit of the present invention.

[0020] Reference numerals: 1, separator; 11, shelving module; 12, separation column; 2, auxiliary unit; 21, closing block; 211, card slot; 212, card block; 213, toggle rod; 22, moving block; 23, pulling rope; 24, slider; 25, rotating plate; 251, permanent magnet; 252, rubber pad; 253, return spring; 26, sliding groove; 3, enrichment unit; 31, support plate; 32, enrichment column; 4, adjustment unit; 41, pushing column; 42, L-shaped rod; 421, vertical rod; 422, mounting spring; 423, friction soft pad; 424, resistance member; 43, pulling spring; 44, closing plate; 441, pressing spring; 442, cross plate; 443, pull rod; 444, conical plug; 445, sealing pad; 446, pressing port. Detailed implementation manners

[0021] To make the above objects, features and advantages of the present invention more obvious and understandable, the following detailed description of the specific implementation manners of the present invention will be given in conjunction with the accompanying drawings of the specification.

[0022] In the following description, many specific details are set forth to facilitate a thorough understanding of the present invention. However, the present invention may be implemented in other ways different from those described herein. Those skilled in the art can make similar generalizations without departing from the connotation of the present invention. Therefore, the present invention is not limited by the specific embodiments disclosed below.

[0023] Secondly, the so-called "one embodiment" or "embodiment" herein refers to a specific feature, structure or characteristic that may be included in at least one implementation manner of the present invention. The appearances of "in one embodiment" in different places in this specification do not all refer to the same embodiment, nor are they separate or alternative embodiments that exclude each other from other embodiments.

[0024] Thirdly, the present invention is described in detail in conjunction with the schematic diagrams. When detailing the embodiments of the present invention, for the convenience of explanation, the cross-sectional views showing the device structure will be enlarged locally out of the general scale, and the schematic diagrams are only examples and should not limit the scope of protection of the present invention herein. In addition, in actual production, three-dimensional spatial dimensions including length, width and depth should be included.

[0025] The following further describes the present invention in conjunction with embodiments.

[0026] Embodiment 1

[0027] Referring to Figure 1 , this is the first embodiment of the present invention. This embodiment provides a specific cell enrichment and magnetic sorting system based on immunomagnetic beads, including a sorter 1, a shelving module 11 and a sorting column 12. The shelving module 11 is installed on one side of the outer wall of the sorter 1. During magnetic sorting, the sorting column 12 is embedded in the shelving module 11, and the permanent magnet 251 in the shelving module 11 forms a magnetic field to complete the magnetic sorting of cells.

[0028] Furthermore, a support plate 31 is installed on the top of the sorter 1, and an enrichment column 32 is installed on the top of the support plate 31. The support plate 31 extends the enrichment column 32 directly above the shelving module 11. During magnetic sorting, the enrichment column 32 can be directly opened, and the liquid after enrichment can be directly dropped onto the sorting column 12 at the bottom.

[0029] Operation process: Pour the cultured cell fluid and immune magnetic beads into the enrichment column 32, and give a certain amount of time for the magnetic beads and cells to be enriched. After the enrichment is completed, open the opening at the bottom of the enrichment column 32, and the enrichment column 32 drips the liquid onto the sorting column 12. The liquid on the sorting column 12 flows through the magnetic field, and the magnetic field adsorbs the cells enriched with the magnetic beads, so that the cells complete magnetic sorting.

[0030] Example 2

[0031] Reference Figures 1 - 5 , which is the second embodiment of the present invention, and this embodiment is different from the first embodiment in that: an auxiliary unit 2 is installed inside the shelf module 11, and the auxiliary unit 2 can effectively solve the problem that the permanent magnet 251 is easy to absorb magnetic dust particles, and an adjustment unit 4 is installed inside the sorter 1, and the adjustment unit 4 can adjust the dripping speed of the enrichment column 32 according to the demand; The auxiliary unit 2 includes a closing block 21 installed on the inner wall of the shelf slot of the shelf module 11. The closing block 21 is arranged according to the inner wall of the shelf slot of the shelf module 11. When not in use, the closing block completely fills and closes the shelf slot of the shelf module 11. A moving block 22 is installed on the outer wall of the closing block 21. A pull rope 23 is installed on the outer wall of the moving block 22. A slider 24 is installed on the other end of the pull rope 23. A rotating plate 25 is movably connected to the inner wall of the shelf module 11 through a pin shaft. A slide groove 26 is opened on the inner wall of the shelf module 11. The slider 24 is movably connected to the rotating plate 25, and its moving block 22 passes through the interior of the shelf module 11 through the slide groove 26, so that the moving block 22 is located on one side of the rotating plate 25. When the cell enrichment is completed and magnetic sorting begins, the sorting column 12 presses the closing block 21, and the movement of the closing block 21 drives the moving block 22 to move. The pull rope 23 on the moving block 22 pulls the slider 24 to move. The movable connection between the slider 24 and the rotating plate 25 enables the pull rope 23 to pull the rotating plate 25 to rotate, so that the rotating plate 25 rotates to one side of the slide groove 26. A return spring 253 is installed on the outer wall of the other side of the rotating plate 25. The other end of the return spring 253 is connected to the inner wall of the shelf module 11, which can be used to restore the rotating plate 25.

[0032] Specifically, a slot 211 is provided at the top of the closing block 21, a block 212 is installed on the inner wall of the shelf module 11, a toggle rod 213 is installed on the top of the block 212, and the top end of the toggle rod 213 extends out of the top of the shelf module 11. When the rotating plate 25 is completely in contact with one side of the slide groove 26, the block 212 is embedded in the slot 211, making the closing block 21 irreversible.

[0033] Furthermore, a permanent magnet 251 is installed on the outer wall of the rotating plate 25, and two groups of rubber pads 252 are installed on the outer wall of the rotating plate 25. The two groups of rubber pads 252 are respectively located on the upper and lower sides of the permanent magnet 251. When the rotating plate 25 rotates and fits with one side of the sliding groove 26, the permanent magnet 251 and the rubber pads 252 are embedded in the sliding groove 26, and the rubber pads 252 slightly protrude into the placing groove of the placing module 11. At this time, the sorting column 12 is clamped by the protruding rubber pads 252, and the permanent magnet 251 is located on both sides of the sorting column 12, so that the sorting column 12 is wrapped by the magnetic field. The rubber pads 252 can be slidably connected to the rotating plate 25 up and down to cooperate with the subsequent adjustment of the dropping speed.

[0034] The remaining structures are the same as those in Embodiment 1.

[0035] Operation process: When the permanent magnet 251 is not in use, the rotating plate 25 retracts inside the placing module 11, and the closing block 21 moves to one side of the sliding groove 26, so that the sliding groove 26 is blocked, keeping the permanent magnet 251 in a dust-free environment. When the permanent magnet 251 is in use, the permanent magnet 251 moves to both sides close to the sorting column 12 along with the rotating plate 25. This way, the placing module 11 will not adsorb some magnetic dust particles due to the permanent magnet 251. When the closing block 21 moves to the limit, the closing block 21 is locked. At this time, the rubber pads 252 clamp the sorting column 12, so that the sorting column 12 does not need to be supported and will not shake during sorting, ensuring the normal progress of the magnetic separation work.

[0036] Embodiment 3

[0037] Refer to Figure 6 , which is the third embodiment of the present invention. The difference between this embodiment and the above embodiments is that the adjusting unit 4 includes a pushing column 41 installed on the outer wall of the closing block 21. One end of the pushing column 41 extends into the inside of the sorter 1. An L-shaped rod 42 is connected to the inner wall of the pushing column 41. A pulling spring 43 is installed at the top of the L-shaped rod 42, and the other end of the L-shaped rod 42 is located at the bottom side of the closing plate 44. The closing plate 44 is installed on the inner wall of the enrichment column 32. As the sorting column 12 is installed and the closing block 21 is pressed and moved by the sorting column 12, the pushing column 41 moves to drive the L-shaped rod 42 to move, so that the L-shaped rod 42 moves to the bottom side of the pressing port 446 of the closing plate 44.

[0038] Further, a vertical rod 421 is installed at the top of the L-shaped rod 42 through a pin shaft. An installation spring 422 connected to the top of the L-shaped rod is installed at the bottom of the vertical rod 421, enabling the vertical rod 421 to bend at the top of the L-shaped rod. When the sorting column 12 presses the closing block 21 to move, the friction soft pad 423 contacts the surface of the sorting column 12, so that the upward movement of the sorting column 12 can drive the L-shaped rod 42 to move. When the closing block 21 moves, the vertical rod 421 receives forces in the opposite directions of the bending direction, preventing the vertical rod 421 from tilting. When the closing block 21 is restored, the closing plate 44 presses against the vertical rod 421, causing the vertical rod 421 to bend and then separate from the closing plate 44.

[0039] Further, a pressing spring 441 is installed on the inner top wall of the closing plate 44. A cross plate 442 is installed at the bottom of the pressing spring 441. A pull rod 443 is installed at the bottom of the cross plate 442. A conical plug 444 is installed at the bottom of the pull rod 443. A sealing gasket 445 is installed on the inner bottom wall of the enrichment column 32. The pressing spring 441 applies a downward pressure on the cross plate 442, and the conical plug 444 is hermetically fitted to the sealing gasket 445, closing the bottom of the enrichment column 32. Only when the sorting column 12 is completely installed, at this time, the closing block 21 and the L-shaped rod 42 that move along with the sorting column 12 move, so that when the sorting column 12 is directly below the enrichment column 32, the L-shaped rod 42 is exactly at the bottom side of the pressing port 446. At this time, pulling the spring 43 can pull the L-shaped rod 42 to move, causing the L-shaped rod 42 and the vertical rod 421 to lift one end of the cross plate 442, and then separating the conical plug 444 and the sealing gasket 445, and then opening the bottom of the enrichment column 32 for uniform liquid dripping. A resistance member 424 is installed at the top of the L-shaped rod 42, and the resistance member 424 is used to offset the pulling force of the pulling spring on the L-shaped rod 42, so that the subsequent movement of the sorting column 12 can adjust the dripping speed, effectively improving the operation difficulty of manual liquid dripping for magnetic separation and effectively reducing the mis-sieving rate.

[0040] Further, one end of the L-shaped rod 42 is located at the bottom side of the closing plate 44, and the other end of the L-shaped rod extends into the inside of the closing block 21 movably. The side wall of the L-shaped rod 42 is kept in contact with the installation surface between the closing block 21 and the pushing column 41, enabling the L-shaped rod 42 to move upward stably.

[0041] All other structures are the same as those in Embodiment 2.

[0042] Operation process: After the sorting column 12 is installed, one end of its L-shaped rod 42 moves to the bottom side of the pressing port 446. At this time, the L-shaped rod 42 is no longer restricted by the bottom wall of the closing plate 44, and the pulling spring 43 pulls the L-shaped rod 42 to move upward. The L-shaped rod 42 pries one end of the cross plate 442 to move upward, so that the other end of the cross plate 442 drives the pull rod 443 to move. The pull rod 443 drives the tapered plug 444 to move, so that the tapered plug 444 is separated from the sealing gasket 445. Then, when the sorting column 12 is directly below the enrichment column 32, the enrichment column 32 starts to drip liquid at the default speed, thus improving the problem of uneven dripping speed caused by repeated manual dripping in the traditional method. When the dripping speed needs to be adjusted, the sorting column 21 can be moved, so that the sorting column drives the L-shaped rod 42 to move, thereby changing the gap between the tapered plug 444 and the sealing gasket 445 to complete the adjustment of accelerating the low speed. And when the dripping is completed, the toggle rod 213 can be pulled. The toggle rod 213 changes the inclination angle of the clamping block 212, so that the restriction of the clamping block 212 on the closing block 21 is cancelled. And at this time, the vertical rod 421 is subjected to the force in the restoring direction of the closing block 21, so that the vertical rod 421 is bent, and then the vertical rod 421 is separated from the closing plate 44, so that the enrichment column 32 is closed again.

[0043] Working principle: When the sorter 1 is in use, the cultured cell solution and magnetic beads are placed in the enrichment column 32, and then a certain time is given for enrichment. After the enrichment is completed, the sorting column 12 is placed on one side of the closing block 21. Then the sorting column 12 presses the closing block 21 to move until the closing block 21 is completely embedded inside the shelving module 11 (that is, when the sorting column 12 moves directly below the enrichment column 32). At this time, the L-shaped rod 42 connected to the closing block 21 moves to directly below the pressing port 446 of the closing plate 44. At this time, the L-shaped rod 42 automatically presses the cross plate 442, so that the other side of the cross plate 442 pulls the tapered plug 444, and then the bottom opening of the enrichment column 32 is opened for uniform dripping. The dripping speed can also be changed by changing the up and down state of the sorting column 12 to change the pressing degree of the L-shaped rod 42 on the cross plate 442; Moreover, the position of the closing block 21 is related to the placement state of the permanent magnet 251. When the closing block 21 is completely embedded in the shelving module 11, its permanent magnet 251 just rotates to both sides of the sorting column 12. When not in use, its permanent magnet 251 rotates back, so as to avoid the permanent magnet 251 being easily adsorbed by magnetic particles when not in use and avoid the change of the magnetic field strength when the permanent magnet 251 is in use.

[0044] The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it; although the present invention has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that: they can still modify the technical solutions described in the foregoing embodiments, or perform equivalent replacements on some of the technical features; and these modifications or replacements will not cause the essence of the corresponding technical solutions to deviate from the protection scope of the technical solutions of the embodiments of the present invention.

Claims

1. A specific cell enrichment and magnetic separation system based on immunomagnetic beads, comprising a separation device (1), a shelf module (11) and a separation column (12), characterized in that: in, The shelf module (11) is installed on the outer wall of the sorter (1), the sorting column (12) is placed on the shelf slot of the shelf module (11), an auxiliary unit (2) is installed inside the shelf module (11), and an adjustment unit (4) is installed inside the sorter (1); The auxiliary unit (2) comprises a closing block (21) mounted on the inner wall of a shelf slot of a shelf module (11); a moving block (22) is mounted on the outer wall of the closing block (21); a pull rope (23) is mounted on the outer wall of the moving block (22); a slider (24) is mounted on the other end of the pull rope (23); a rotating plate (25) is movably connected to the inner wall of the shelf module (11) via a pin shaft; and a slide groove (26) is provided on the inner wall of the shelf module (11).

2. A specific cell enrichment and magnetic separation system based on immunomagnetic beads according to claim 1, characterized in that: A slot (211) is provided on the top of the closing block (21), a block (212) is installed on the inner wall of the shelf module (11), a toggle rod (213) is installed on the top of the block (212), and the top end of the toggle rod (213) extends out of the top of the shelf module (11).

3. The specific cell enrichment and magnetic separation system based on immunomagnetic beads according to claim 2, characterized in that: A permanent magnet (251) is mounted on the outer wall of the rotating plate (25), and two groups of rubber pads (252) are mounted on the outer wall of the rotating plate (25), and the two groups of rubber pads (252) are respectively located on the upper and lower sides of the permanent magnet (251), and when the rotating plate (25) rotates, the permanent magnet and the rubber pad (252) are embedded in the slide groove (26), and the rubber pad (252) slightly protrudes from the shelf groove of the shelf module (11), and a return spring (253) is mounted on the outer wall on the other side of the rotating plate (25), and the other end of the return spring (253) is connected to the inner wall of the shelf module (11).

4. The specific cell enrichment and magnetic separation system based on immunomagnetic beads according to claim 3, characterized in that: A support plate (31) is installed on the top of the separator (1), and an enrichment column (32) is installed on the top of the support plate (31). The enrichment column (32) is located directly above the shelf module (11).

5. The specific cell enrichment and magnetic separation system based on immunomagnetic beads according to claim 4, characterized in that: The regulating unit (4) comprises a pushing column (41) mounted on the outer wall of the closing block (21); an L-shaped rod (42) is connected to the inner wall of the pushing column (41); a pulling spring (43) is mounted on one end of the L-shaped rod (42); and a closing plate (44) is mounted on the inner wall of the enrichment column (32).

6. The specific cell enrichment and magnetic separation system based on immunomagnetic beads according to claim 5, characterized in that: A vertical rod (421) is installed at the top of the L-shaped rod (42), a mounting spring (422) connected to the top of the L-shaped rod (42) is installed at the bottom of the vertical rod (421), a friction pad (423) is installed at the other end of the L-shaped rod (42), and a resistance member (424) is installed at the top of the L-shaped rod (42).

7. The specific cell enrichment and magnetic separation system based on immunomagnetic beads according to claim 6, characterized in that: A pressing spring (441) is installed on the inner top wall of the closing plate (44), a horizontal plate (442) is installed on the bottom of the pressing spring (441), a pull rod (443) is installed on the bottom of the horizontal plate (442), a conical plug (444) is installed on the bottom of the pull rod (443), and a sealing gasket (445) is installed on the inner bottom wall of the enrichment column (32).

8. The specific cell enrichment and magnetic separation system based on immunomagnetic beads according to claim 7, characterized in that: The pressing spring (441) applies downward pressure to the horizontal plate (442), the conical plug (444) is sealed against the sealing gasket (445), and a pressing opening (446) is provided at the bottom of the closing plate (44).

9. The specific cell enrichment and magnetic separation system based on immunomagnetic beads according to claim 8, characterized in that: One end of the L-shaped rod (42) is located on the bottom side of the closing plate (44), and the other end of the L-shaped rod (42) movably extends to the inside of the closing block (21).

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