A specific cell enrichment and magnetic separation system based on immunomagnetic beads

Abstract

The present invention relates to the technical field of cell enrichment and sorting equipment, and in particular to a specific cell enrichment and magnetic sorting system based on immunomagnetic beads. The present invention mainly addresses the inconvenience of using existing sorters and proposes the following technical solutions: the shelf module is mounted on the outer wall of the sorter, the sorting column is placed on the shelf slot of the shelf module, an auxiliary unit is installed inside the shelf module, and an adjustment unit is installed inside the sorter, the outer wall of the closing block is mounted with a moving block, the outer wall of the moving block is mounted with a pull rope, the other end of the pull rope is mounted with a slider, and the inner wall of the shelf module is movably connected to a rotating plate via a pin; the present invention changes the placement state of the permanent magnet when it is not in use and when it is in use, so that magnetic dust particles are not adsorbed on the shelf module; the permanent magnet can be firmly clamped when the sorting column is installed, and the sorting column can be moved upward after installation to adjust the dripping speed, thereby reducing the operational difficulty of magnetic sorting.

Description

Technical Field

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

[0002] Specific cell enrichment and magnetic separation is a common technique in biomedical research used to isolate specific cell types from mixed cell populations. This technology relies on the interaction of magnetic particles (magnetic beads) and magnetic fields. By attaching specific antibodies or ligands to the beads, they bind specifically to the target cells, thereby achieving the isolation and enrichment of target cells.

[0003] When using existing separators, the enriched liquid is usually magnetically separated by dripping onto a separation column. The dripping speed needs to be controlled to be slow to ensure that the dripping liquid can be fully absorbed and separated by the magnetic field in the separation column.

[0004] The above operation requires workers to repeatedly use a special dropper to perform the dripping operation. When performing magnetic separation on a large volume of enriched liquid, the workers have a high workload and it is difficult to always ensure the correct dripping speed, which causes the actual magnetic separation misscreening rate to fluctuate. In addition, the permanent magnets of the existing separator are fixed close to both sides of the separation column and cannot be adjusted. When not in use, the wall close to the permanent magnet side is prone to accumulate magnetic dust and debris, affecting the magnetic field strength and direction, and increasing the actual magnetic separation misscreening rate of the separator. Summary of the Invention

[0005] The purpose of this section is to summarize some aspects of the embodiments of the present invention and briefly introduce some preferred embodiments. Some simplifications or omissions may be made in this section and the abstract and title of this application to avoid obscuring the purpose of this section, the abstract and the title of the invention, and such simplifications or omissions should not be used to limit the scope of the present invention.

[0006] In view of the above-mentioned shortcomings of the prior art, the present invention provides a subject of a specific cell enrichment and magnetic separation system based on immunomagnetic beads, which can effectively solve the problem of unstable misscreening rate of magnetic separation in the prior art.

[0007] To achieve the above objectives, the present invention is implemented through the following technical solutions:

[0008] The present invention provides a specific cell enrichment and magnetic separation system based on immunomagnetic beads, comprising: a separator, a shelf module and a separation column, wherein the shelf module is mounted on the outer wall of the separator, the separation column is placed on the shelf slot of the shelf module, an auxiliary unit is mounted inside the shelf module, and an adjustment unit is mounted inside the separator;

[0009] The auxiliary unit includes a closing block installed on the inner wall of the shelving slot of the shelving 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 shelving module is movably connected to a rotating plate through a pin shaft, and a sliding groove is opened on the inner wall of the shelving module.

[0010] Furthermore, a slot is provided on the top of the closing block, a block is installed on the inner wall of the shelf module, a toggle rod is installed on the top of the block, and the top end of the toggle rod extends out of the top of the shelf module.

[0011] 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, its permanent magnet and rubber pads are embedded in the slide groove, and the rubber pads slightly protrude in the shelf groove of the shelf module, and a return spring is installed on the outer wall of 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.

[0012] 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.

[0013] Furthermore, the adjustment unit includes a push column installed on the outer wall of the closing block, the inner wall of the push column is connected to an L-shaped rod, one end of the L-shaped rod is installed with a pull spring, and the inner wall of the enrichment column is installed with a closing plate.

[0014] 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.

[0015] 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.

[0016] Furthermore, the pressing spring applies downward pressure to the transverse plate, the conical plug is sealed and fitted on the sealing gasket, and a pressing port is provided at the bottom of the closing plate.

[0017] 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.

[0018] Beneficial effects

[0019] Compared with the prior art, the technical solution provided by the present invention has the following beneficial effects:

[0020] 1. Change the placement of the permanent magnet when it is not in use and when it is in use, so that magnetic dust particles will not be adsorbed on the shelf module, ensuring that the magnetic field strength and direction remain constant during each magnetic separation, effectively reducing the false screening rate of magnetic separation;

[0021] Second, the separation column can be firmly clamped when it is installed, so that the separation column will not shake when dripping liquid, and the separation column always remains on the same side of the permanent magnet, thereby improving the effect of magnetic separation;

[0022] 3. After the separation column is installed, it can be located directly below the enrichment column. The bottom of the enrichment column automatically starts to drip at a uniform speed. The position of the separation column can be moved to adjust the dripping speed, which improves the defects of manual dripping, such as high labor intensity and fluctuation of manual dripping speed. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] To more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are only some embodiments of the present invention. Those skilled in the art can also derive other drawings based on these drawings without inventive effort.

[0024] Figure 1 It is an overall schematic diagram of the present invention;

[0025] Figure 2 for Figure 1 A schematic diagram of the structure at center A;

[0026] Figure 3 is a schematic diagram of a shelving module of the present invention;

[0027] Figure 4 for Figure 3 A magnified schematic diagram of the structure at point B in the middle.

[0028] Figure 5 Schematic diagram of the auxiliary unit of the present invention.

[0029] Figure 6 Schematic diagram of the regulating unit of the present invention.

[0030] 1. Sorting unit; 2. Auxiliary unit; 3. Closing block; 4. Slot; 5. Block; 6. Push rod; 7. Moving block; 8. Pull rope; 9. Slider; 10. Rotating plate; 11. Permanent magnet; 12. Rubber pad; 13. Return spring; 14. Slide; 15. Rotating plate; 16. Permanent magnet; 17. Rubber pad; 18. Return spring; 19. Slide; 20. Enrichment unit; 21. Support plate; 22. Enrichment column; 22. Adjustment unit; 23. Push column; 24. L-shaped rod; 25. Vertical rod; 26. Friction pad; 27. Resistance member; 28. Pull spring; 29. ​​Closing plate; 30. Pressing spring; 31. Pressing plate; 32. Pressing column; 33. Pulling rod; 34. Conical plug; 35. Sealing pad; 36. Pressing port. DETAILED DESCRIPTION

[0031] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the specific embodiments of the present invention are described in detail below with reference to the accompanying drawings.

[0032] In the following description, many specific details are set forth to facilitate a full understanding of the present invention. However, the present invention may also be implemented in other ways different from those described herein. Those skilled in the art may make similar generalizations without violating the connotation of the present invention. Therefore, the present invention is not limited to the specific embodiments disclosed below.

[0033] Secondly, the term "one embodiment" or "embodiment" herein refers to a specific feature, structure, or characteristic that may be included in at least one implementation of the present invention. The phrase "in one embodiment" appearing in various places throughout this specification does not necessarily refer to the same embodiment, nor does it refer to a separate or selective embodiment that is mutually exclusive of other embodiments.

[0034] Furthermore, the present invention is described in detail with reference to schematic diagrams. For ease of illustration, when describing the embodiments of the present invention, cross-sectional views illustrating device structures may be partially enlarged and not to scale. Furthermore, the schematic diagrams are merely illustrative and should not limit the scope of protection of the present invention. Furthermore, in actual production, the three-dimensional dimensions of length, width, and depth should be included.

[0035] The present invention will be further described below with reference to the embodiments.

[0036] Example 1

[0037] Reference Figure 1, which is the first embodiment of the present invention, provides a specific cell enrichment and magnetic sorting system based on immunomagnetic beads, including a sorter 1, a shelf module 11 and a sorting column 12. The shelf module 11 is installed on one side of the outer wall of the sorter 1. When performing magnetic sorting, the sorting column 12 is embedded in the shelf module 11, and the permanent magnet 251 in the shelf module 11 forms a magnetic field to complete the magnetic sorting of cells.

[0038] 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 and installs it directly above the shelving module 11. When performing magnetic separation, the enrichment column 32 can be directly opened and the enriched liquid can be directly dripped onto the sorting column 12 on the bottom side.

[0039] 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, the opening at the bottom of the enrichment column 32 is opened, 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 by the magnetic beads, so that the cells complete magnetic sorting.

[0040] Example 2

[0041] Reference Figure 1-Figure 5 , which is the second embodiment of the present invention. This embodiment differs from the first embodiment in that: an auxiliary unit 2 is installed inside the shelf module 11, which can effectively solve the problem that the permanent magnet 251 easily absorbs magnetic dust particles, and an adjustment unit 4 is installed inside the sorter 1, which can adjust the dripping speed of the enrichment column 32 according to demand;

[0042] The auxiliary unit 2 includes a closing block 21 mounted 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 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. A slide groove 26 is opened on the inner wall of the shelf module 11.

[0043] The slider 24 is movably connected to the rotating plate 25, and its moving block 22 passes through the interior of the shelving 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 the 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 shelving module 11, which can be used to restore the rotating plate 25.

[0044] 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.

[0045] 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, 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 and fits against one side of the slide 26, its permanent magnet 251 and rubber pad 252 are embedded in the slide 26, and the rubber pad 252 protrudes slightly in the shelving groove of the shelving module 11. At this time, the sorting column 12 is clamped by the protruding rubber pad 252, and at this time the permanent magnet 251 is located on both sides of the sorting column 12, so that the sorting column 12 is wrapped in the magnetic field, and the rubber pad 252 can be slid up and down and connected to the rotating plate 25 to cooperate with the subsequent dripping speed adjustment.

[0046] The rest of the structure is the same as that of Example 1.

[0047] Operation process: When the permanent magnet 251 is not in use, its rotating plate 25 is retracted inside the shelving module 11, and the closing block 21 moves to the side of the slide 26, so that the slide 26 is blocked, so that the permanent magnet 251 maintains a dust-free environment. When the permanent magnet 251 is in use, the permanent magnet 251 moves with the rotating plate 25 to the two sides close to the sorting column 12. This method prevents the shelving module 11 from absorbing some magnetic dust particles due to the permanent magnet 251, and when the closing block 21 moves to the limit, the closing block 21 is locked. At this time, the rubber pad 252 clamps the sorting column 12, so that the sorting column 12 does not need support and will not shake during sorting, ensuring the normal progress of the magnetic sorting work.

[0048] Example 3

[0049] Reference Figure 6, which is the third embodiment of the present invention. This embodiment is different from the above embodiments in that: the adjustment 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 interior of the sorter 1, and the inner wall of the pushing column 41 is connected with an L-shaped rod 42, the top of the L-shaped rod 42 is installed with a pulling spring 43, and the other end of the L-shaped rod 42 is located on the bottom side of the closing plate 44, and the inner wall of the enrichment column 32 is installed with a closing plate 44. As the sorting column 12 is installed, when the closing block 21 is pressed and moved by the sorting column 12, its 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.

[0050] Furthermore, a vertical rod 421 is installed at the top of the L-shaped rod 42 through a pin shaft, and a mounting spring 422 connected to the top of the L-shaped rod is installed at the bottom of the vertical rod 421, so that the vertical rod 421 can bend at the top of the L-shaped rod. When the sorting column 12 presses the closing block 21 to move, the friction 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, and when the closing block 21 moves, the vertical rod 421 is subjected to a force in the opposite direction of the bending, so that the vertical rod 421 will not tilt, and when the closing block 21 recovers, the closing plate 44 contacts the vertical rod 421, so that the vertical rod 421 is bent, and then separated from the closing plate 44.

[0051] Furthermore, 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; the pressing spring 441 applies downward pressure to the horizontal plate 442, and the conical plug 444 is sealed and fits against the sealing gasket 445, so that the bottom of the enrichment column 32 is closed. Only when the sorting column 12 is installed, the closing block 21 and the L-shaped rod 42 that move with the sorting column 12 move, so that the sorting column 12 is located in the enrichment column. When the enrichment column 32 is directly below the L-shaped rod 42, its L-shaped rod 42 is located at the bottom side of the pressing port 446. At this time, the spring 43 can be pulled to pull the L-shaped rod 42 to move, so that the L-shaped rod 42 and the vertical rod 421 lift one end of the horizontal plate 442, thereby separating the conical plug 444 and the sealing gasket 445, and then opening the bottom of the enrichment column 32 for uniform dripping. A resistance member 424 is installed on the top of the L-shaped rod 42, and the resistance member 424 is used to offset the pulling of the 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 operational difficulty of manual dripping for magnetic separation, and effectively reducing the misscreening rate.

[0052] Furthermore, 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 is movably extended to the interior of the closing block 21, and the side wall of the L-shaped rod 42 is kept in contact with the mounting surface between the closing block 21 and the push column 41, so that the L-shaped rod 42 can move upward stably.

[0053] The rest of the structure is the same as that of Example 2.

[0054] 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. The spring 43 is pulled to pull the L-shaped rod 42 upward. The L-shaped rod 42 pries one end of the cross plate 442 upward, so that the other end of the cross plate 442 drives the pull rod 443 to move. The pull rod 443 drives the conical plug 444 to move, so that the conical plug 444 is separated from the sealing gasket 445. Then, when the sorting column 12 is located directly below the enrichment column 32, the enrichment column 32 starts to drip at the default speed, thereby improving the dripping caused by traditional manual repeated dripping. In order to solve the problem of uneven liquid speed, 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, and completing the low-speed acceleration adjustment. When the dripping is completed, the toggle rod 213 can be pulled to change the inclination angle of the block 212, thereby canceling the restriction of the block 212 on the closing block 21. At this time, the vertical rod 421 is subjected to the force in the recovery direction of the closing block 21, so that the vertical rod 421 is bent, thereby separating the vertical rod 421 from the closing plate 44, and the enrichment column 32 is re-sealed.

[0055] Working principle: When the sorter 1 is used, the cultured cell fluid and magnetic beads are placed in the enrichment column 32, and then a certain amount of time is given for enrichment. After the enrichment is completed, the sorting column 12 is placed on one side of the closing block 21, and then the sorting column 12 presses the closing block 21 to move until the closing block 21 is completely embedded in the interior of the shelving module 11 (that is, when the sorting column 12 moves to 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 horizontal plate 442, so that the other side of the horizontal plate 442 pulls the conical plug 444, thereby opening the bottom opening of the enrichment column 32 for uniform dripping. The degree of pressure of the L-shaped rod 42 on the horizontal plate 442 can also be changed by moving the sorting column 12 up and down, thereby changing the dripping speed.

[0056] 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 is rotated to both sides of the sorting column 12. When not in use, its permanent magnet 251 is rotated back, thereby preventing the permanent magnet 251 from easily adsorbing magnetic particles when not in use and preventing the magnetic field strength of the permanent magnet 251 from changing when in use.

[0057] The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit the same. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, 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 various embodiments of the present invention.

Claims

1. A specific cell enrichment and magnetic separation system based on immunomagnetic beads, comprising a separator (1), a shelf module (11) and a separation column (12), characterized in that: in, The shelving module (11) is installed on the outer wall of the sorter (1), the sorting column (12) is placed on the shelving slot of the shelving module (11), an auxiliary unit (2) is installed inside the shelving 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 the shelf slot of the 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); the inner wall of the shelf module (11) is movably connected to a rotating plate (25) via a pin shaft; and a sliding groove (26) is provided on the inner wall of the shelf module (11); A support plate (31) is installed on the top of the separator (1), an enrichment column (32) is installed on the top of the support plate (31), and the enrichment column (32) is located directly above the shelving module (11); 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); 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); 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); The pressing spring (441) applies downward pressure to the transverse plate (442), the conical plug (444) is sealed and fitted on the sealing gasket (445), and a pressing port (446) is provided at the bottom of the closing plate (44).

2. The specific cell enrichment and magnetic separation system based on immunomagnetic beads according to claim 1, characterized in that: A card slot (211) is provided on the top of the closing block (21), a card block (212) is installed on the inner wall of the shelf module (11), a toggle rod (213) is installed on the top of the card 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: The outer wall of the rotating plate (25) is installed with a permanent magnet (251), and the outer wall of the rotating plate (25) is installed with two groups of rubber pads (252), 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 the outer wall of the other side of the rotating plate (25) is installed with a return spring (253), 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: 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 (42) is movably extended to the interior of the closing block (21).

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