Circulating tumor cell step-by-step separation device

Abstract

The invention discloses a circulating tumor cell step-by-step separation device which comprises a material barrel, a separation assembly is arranged at the bottom end of the material barrel, the separation assembly comprises a plurality of spiral pipes connected to the bottom end of the material barrel through through holes, all the spiral pipes are jointly and uniformly arranged in the circumferential direction, and a center rod is coaxially connected to the bottom end of the material barrel; a fixing frame is arranged on the outer side of the spiral pipe, multiple sets of magnetic bead frames are arranged on the fixing frame and the center rod together, the set distance of each set of magnetic bead frames is equal to the screw pitch of the spiral pipe, separation magnetic beads are arranged on the inner side of each magnetic bead frame, and the inner sides of the magnetic bead frames make contact with the outer side of the spiral pipe; according to the separation assembly provided by the invention, circulating cells are separated step by step by arranging the spiral pipe, and the movement speed of the cells in the separation process can be reduced through the spiral arrangement, so that the situation that in a conventional separation mode, the movement speed of non-target cells is caused by vertical movement of the cells, and the target cells are separated in advance due to too large impact is avoided.

Description

Technical Field

[0001] The present invention relates to the technical field of cell separation, and more specifically, to a circulating tumor cell step-by-step separation device. Background Art

[0002] Circulating tumor cell isolation is a technology for separating and detecting tumor cells from the blood. It is based on the unique characteristics of circulating tumor cells (CTCs), namely that tumor cells can enter the blood circulation from the primary tumor and form metastases in distant tissues. The purpose of circulating tumor cell isolation is to provide tumor diagnosis, prognosis and treatment response monitoring by isolating and analyzing CTCs.

[0003] However, when existing circulating tumor cell step-by-step separation devices use immunomagnetic beads for adsorption separation, some circulating tumor cells are easily impacted by non-labeled cells, causing them to escape from the magnetic beads and fall out prematurely, thereby reducing the final separation amount and the tumor cell separation effect of the device. Summary of the Invention

[0004] The present invention provides a circulating tumor cell step-by-step separation device to solve the problem in the prior art that when the circulating tumor cell step-by-step separation device uses immunomagnetic beads for adsorption separation, some circulating tumor cells are easily impacted by non-labeled cells, causing them to escape from the magnetic beads and fall out prematurely, thereby reducing the tumor cell separation effect of the device.

[0005] In order to achieve the above object, the present invention provides the following technical solutions:

[0006] A circulating tumor cell step-by-step separation device comprises a material barrel, a separation assembly is provided at the bottom end of the material barrel, the separation assembly comprises a plurality of spiral tubes connected to the bottom end of the material barrel through a through hole, all the spiral tubes are uniformly arranged along the circumferential direction, a center rod is coaxially connected to the bottom end of the material barrel, a fixing frame is provided on the outside of the spiral tube, a plurality of groups of magnetic bead racks are provided on the fixing frame and the center rod, the spacing between each group of magnetic bead racks is equal to the pitch of the spiral tube, separation magnetic beads are provided on the inside of the magnetic bead rack, and the inside of the magnetic bead rack is in contact with the outside of the spiral tube.

[0007] Preferably, the bottom end of the central rod is coaxially connected to a connecting plate, a plurality of liquid guide holes are opened on the connecting plate, each liquid guide hole is connected to the bottom end of a spiral tube, and the bottom end of the connecting plate is connected to a liquid guide cover.

[0008] Preferably, a cover body is provided on the rotation card at the bottom end of the fixing frame, the liquid guide cover is rotationally provided in the cover body, and the circumferential angle of the bottom surface of the liquid guide cover is 120 degrees.

[0009] Preferably, an orientation assembly is provided between the fixing frame and the cover body, and the orientation assembly includes an orientation plate provided outside any fixing frame, three sliding plates provided outside the cover body, a positioning fork provided at the top of the sliding plate, and the orientation plate is clamped at the top of the positioning fork.

[0010] Preferably, three groups of guide plates are provided on the outside of the cover body, and each directional plate is slidably clamped between a group of guide plates. The sliding clamp on the outside of the cover body is provided with an elastic ring, and the inner side of the elastic ring contacts one end of the sliding plate.

[0011] Preferably, a bottom bracket is provided at the bottom end of the cover body, and three collecting grooves are provided on the bottom wall of the bottom bracket. The central angle of each collecting groove is 120 degrees, and the card plate provided at the bottom end of the cover body is slidably clamped on the outside of the bottom bracket.

[0012] Preferably, a switching assembly is provided at the top of the material barrel, and the switching assembly includes a support arm provided on the outside of the material barrel, the free end of the support arm is connected to a motor, the output shaft end of the motor is coaxially connected to a connecting rod, and the bottom end of the connecting rod is coaxially connected to a fan-shaped plate, and the central angle of the fan-shaped plate is 240 degrees.

[0013] Preferably, a delay component is provided on the inner bottom wall of the material barrel, and the delay component includes a cover provided on the through hole of the material barrel, and the top end of each cover is connected to a plug plate through a movable rod.

[0014] Preferably, a plurality of fixing frames are provided on the outside of the material barrel, an end plate is provided at one end of the inserting plate, and one end of the inner wall of the fixing frame is connected to one side of the end plate through a spring.

[0015] Preferably, a top plate is coaxially connected to the connecting rod, a directional block is hinged at the free end of the top plate, one end of the plug plate is clamped in a directional slot opened at one end of the directional block, an electromagnet is provided at the free end of the top plate, and a magnet is provided at the opposite end of the directional block and the top plate.

[0016] The principle and beneficial effects of this technical solution:

[0017] (1) The separation component provided in the present invention separates circulating cells step by step by providing a spiral tube. The spiral setting can reduce the cell movement speed during the separation process, avoiding the movement speed of non-target cells caused by vertical movement of cells in conventional separation methods and the premature separation of target cells caused by excessive impact. When using the separation component, the switching component is driven to open any cover in the delay component, so that the spiral tube connected to the bottom end of the through hole is connected to the inside of the material barrel. At this time, the sample to be separated in the material barrel will flow along the spiral tube. When the sample passes through the magnetic bead rack during the flow process, the separation magnetic beads provided on the inner side of the magnetic bead rack will attract the circulating tumor cells and make them adhere to the inner wall of the spiral tube. At the same time, since there are multiple groups of magnetic bead racks in the vertical direction, the sample will undergo multiple separations during the flow process, thereby greatly reducing the possibility of premature separation of circulating tumor cells.

[0018] (2) The directional assembly provided in the present invention can change the angle between the fixed frame and the cover body, so that the device can change the conductive relationship between the liquid guide cover and different collection slots when collecting non-target cells, circulating tumor cells and cleaning flushing fluid, avoiding the need to manually replace the receiving container during the separation process. When the fixed frame needs to be rotated, the elastic ring provided on the outer side of the cover body is slid downward so that the inner side of the elastic ring no longer contacts one end of the sliding plate. At this time, the sliding plate will slide along the guide plate, so that the positioning fork at the top of the sliding plate is separated from the contact with the directional plate. At this time, the fixed frame can be rotated to connect the liquid guide cover with different collection slots on the bracket.

[0019] (3) The switching assembly provided in the present invention can adjust the conduction between the material barrel and different spiral tubes, thereby reducing the separation pressure of the spiral tubes when separating a large number of cells at a time, and further reducing the probability of premature separation of circulating tumor cells. When the switching assembly is used, the motor is started. When the motor is started, the electromagnet is energized for a period of time, causing the directional block to deflect upward and disengage from the current position of the plug plate. Then, the motor will drive the connecting rod to rotate 120 degrees. When the gap opened on the fan-shaped plate is aligned with another through hole, the motor is stopped, and the plug plate will be reset under the elastic force of the spring, so that the plug plate is stuck in the directional block, thereby locking the position of the rotating rod. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 It is a schematic diagram of the overall structure of the present invention;

[0021] Figure 2 This is a schematic diagram of the structure after disassembly of the present invention;

[0022] Figure 3 for Figure 2 Schematic diagram of the enlarged structure of area A in the middle;

[0023] Figure 4 for Figure 2 Schematic diagram of the enlarged structure of the middle B area;

[0024] Figure 5 for Figure 2 Schematic diagram of the enlarged structure of the middle C region;

[0025] Figure 6 It is a schematic diagram of the structure after cutting of the present invention;

[0026] The figure marks in the drawings of the specification include: 1. material barrel; 2. sealing cover; 3. connecting rod; 4. fan-shaped plate; 5. liquid guide hole; 6. cover body; 7. motor; 8. support arm; 9. connecting plate; 10. liquid guide cover; 11. plug plate; 12. end plate; 13. moving rod; 14. top plate; 15. electromagnet; 16. fixed frame; 17. spring; 18. orientation block; 19. orientation slot; 20. spiral tube; 21. magnetic bead rack; 22. fixed frame; 23. orientation plate; 24. positioning fork; 25. guide plate; 26. sliding plate; 27. elastic ring; 28. collecting trough; 29. clamping plate; 30. bottom support; 31. center rod. DETAILED DESCRIPTION

[0027] The present invention will be further described in detail below with reference to the accompanying drawings and embodiments:

[0028] Example:

[0029] like Figures 1 to 6 As shown, the present invention provides a circulating tumor cell step-by-step separation device, including a material barrel 1, a separation component is provided at the bottom end of the material barrel 1, the separation component includes a plurality of spiral tubes 20 connected to the bottom end of the material barrel 1 through a through hole, all the spiral tubes 20 are uniformly arranged along the circumferential direction, the bottom end of the material barrel 1 is coaxially connected to a center rod 31, a fixing frame 22 is provided on the outside of the spiral tube 20, and multiple groups of magnetic bead racks 21 are provided on the fixing frame 22 and the center rod 31, and the spacing between each group of magnetic bead racks 21 is equal to the pitch of the spiral tube 20, and separation magnetic beads are provided on the inner side of the magnetic bead rack 21, and the inner side of the magnetic bead rack 21 is in contact with the outer side of the spiral tube 20.

[0030] like Figure 2 and Figure 4 As shown, the bottom end of the center rod 31 is coaxially connected to a connecting plate 9, and a plurality of liquid guide holes 5 are opened on the connecting plate 9. Each liquid guide hole 5 is connected to the bottom end of a spiral tube 20, and the bottom end of the connecting plate 9 is connected to a liquid guide cover 10.

[0031] like Figure 2 and Figure 4 As shown, the bottom end of the fixing frame 22 is rotatably clamped with a cover body 6, and the liquid guide cover 10 is rotatably clamped in the cover body 6. The circumferential angle of the bottom surface of the liquid guide cover 10 is 120 degrees.

[0032] like Figure 2 、 Figure 4 and Figure 5 As shown, an orientation assembly is provided between the fixing frame 22 and the cover body 6, and the orientation assembly includes an orientation plate 23 provided on the outside of any fixing frame 22, three sliding plates 26 are provided on the outside of the cover body 6, and a positioning fork 24 is provided on the top of the sliding plate 26, and the orientation plate 23 is clamped on the top of the positioning fork 24.

[0033] like Figure 2 、 Figure 4 and Figure 5 As shown, three groups of guide plates 25 are provided on the outside of the cover body 6, and each directional plate 23 is slidably clamped between a group of guide plates 25. An elastic ring 27 is slidably clamped on the outside of the cover body 6, and the inner side of the elastic ring 27 contacts one end of the sliding plate 26.

[0034] The directional component can change the angle between the fixed frame 22 and the cover body 6, so that the device can change the conductive relationship between the liquid-conducting cover 10 and different collection slots 28 when collecting non-target cells, circulating tumor cells and cleaning flushing fluid, avoiding the need to manually replace the receiving container during the separation process. When the fixed frame 22 needs to be rotated, the elastic ring 27 sleeved on the outside of the cover body 6 is slid downward so that the inner side of the elastic ring 27 no longer contacts one end of the sliding plate 26. At this time, the sliding plate 26 will slide along the guide plate 25, so that the positioning fork 24 at the top of the sliding plate 26 is separated from the contact with the directional plate 23. At this time, the fixed frame 22 can be rotated to make the liquid-conducting cover 10 conductive with different collection slots 28 on the bracket.

[0035] like Figure 2 and Figure 5 As shown, a base 30 is provided at the bottom end of the cover body 6, and three collecting grooves 28 are opened on the bottom wall of the base 30. The central angle of each collecting groove 28 is 120 degrees. The clamping plate 29 provided at the bottom end of the cover body 6 is slidably clamped on the outside of the base 30.

[0036] like Figure 1 and Figure 2 As shown, a switching assembly is provided at the top of the material barrel 1, and the switching assembly includes a support arm 8 provided on the outside of the material barrel 1, the free end of the support arm 8 is connected to the motor 7, the output shaft end of the motor 7 is coaxially connected to the connecting rod 3, and the bottom end of the connecting rod 3 is coaxially connected to the fan-shaped plate 4, and the central angle of the fan-shaped plate 4 is two hundred and forty degrees.

[0037] like Figure 1 and Figure 3 As shown, a delay assembly is provided on the inner bottom wall of the material barrel 1 , and the delay assembly includes a cover 2 covering the through hole of the material barrel 1 , and the top of each cover 2 is connected to a plug plate 11 through a moving rod 13 .

[0038] like Figure 1 and Figure 3 As shown, a plurality of fixing frames 16 are provided on the outside of the material barrel 1 , an end plate 12 is provided on one end of the inserting plate 11 , and one end of the inner wall of the fixing frame 16 is connected to one side of the end plate 12 via a spring 17 .

[0039] like Figure 1 and Figure 3 As shown, a top plate 14 is coaxially connected to the connecting rod 3, an orientation block 18 is hinged at the free end of the top plate 14, one end of the insert plate 11 is clamped in an orientation slot 19 opened at one end of the orientation block 18, an electromagnet 15 is provided at the free end of the top plate 14, and a magnet is provided at the opposite end of the orientation block 18 and the top plate 14.

[0040] The switching assembly can adjust the material barrel 1 and the different spiral tubes 20 to conduct, thereby reducing the separation pressure of the spiral tube 20 when separating a large number of cells at a time, and further reducing the probability of premature separation of circulating tumor cells. When the switching assembly is used, the motor 7 is started. When the motor 7 is started, the electromagnet 15 is energized for a period of time, so that the electromagnet 15 set at the free end of the top plate 14 squeezes the magnet set at the opposite end of the directional block 18 through repulsive force. At this time, the directional block 18 will deflect upward to break away from the card setting of the current position plug plate 11, and then the motor 7 That is, it will drive the connecting rod 3 to rotate 120 degrees. During the rotation of the connecting rod 3, the electromagnet 15 will be powered off. At this time, the directional block 18 will be reset. When the notch opened on the sector plate 4 is aligned with the other through hole, the motor 7 will be stopped. The directional block 18 will also squeeze the plugboard 11 so that the end plate 12 set at one end of the plugboard 11 squeezes the spring 17 until the notch on the directional block 18 is aligned with the plugboard 11. At this time, the plugboard 11 will be reset under the elastic force of the spring 17, so that the plugboard 11 is stuck in the directional block 18, thereby locking the position of the rotating rod.

[0041] The specific usage and function of this embodiment are as follows:

[0042] The separation component provided in the present invention can separate the circulating cells step by step by providing a spiral tube 20. The spiral setting can reduce the cell movement speed during the separation process, avoiding the vertical movement of cells in the conventional separation method, which leads to the movement speed of non-target cells and the premature separation of target cells due to excessive impact. When using the separation component, the switching component is driven to open any cover 2 in the delay component, so that the spiral tube 20 connected to the bottom end of the through hole is connected to the inside of the material barrel 1. At this time, the sample to be separated in the material barrel 1 will flow along the spiral tube 20. During the sample flow process, When passing through the magnetic bead rack 21, the separation magnetic beads arranged inside the magnetic bead rack 21 will attract the circulating tumor cells and make them adhere to the inner wall of the spiral tube 20. At the same time, since multiple sets of magnetic bead racks 21 are arranged in the vertical direction, the sample will undergo multiple separations during the flow process, thereby greatly reducing the possibility of premature separation of circulating tumor cells. Non-target cells will continue to flow downward with the sample and flow into the liquid guide cover 10 under the guidance of the liquid guide hole 5 on the connecting plate 9 connected to the bottom end of the central rod. Finally, they are introduced into the collection tank 28 connected to the bottom end of the liquid guide cover 10 for collection;

[0043] After standing for a while until the non-target cells enter the collection tank 28, the directional component is unlocked, and then the fixing frame 22 is rotated along the top of the cover body 6. At this time, the material barrel 1 connected to the top of the fixing frame 22 will drive the connecting plate 9 coaxially connected to its bottom through the center rod to rotate, and the liquid guide cover 10 at the bottom end of the connecting plate 9 will also rotate synchronously in the cover body 6. After rotating 120 degrees, the directional component is re-locked. At this time, the liquid guide cover 10 is connected to the other collection tank 28 at the bottom of the base 30. The circulating tumor cells can be released by removing the magnetic bead rack 21 and finally collected through the collection tank 28.

[0044] The above is only an embodiment of the present invention, and the common knowledge such as the specific technical solutions and / or characteristics in the solution are not described in detail here. It should be pointed out that for those skilled in the art, without departing from the technical solution of the present invention, several variations and improvements can be made, which should also be regarded as the scope of protection of the present invention, and these will not affect the effect of the implementation of the present invention and the practicality of the patent. The scope of protection required by this application shall be based on the content of its claims, and the specific implementation methods and other records in the description can be used to interpret the content of the claims.

Claims

1. A circulating tumor cell separation device, characterized by: The invention comprises a material barrel (1), wherein the bottom end of the material barrel (1) is provided with a separation component, wherein the separation component comprises a plurality of spiral tubes (20) connected to the bottom end of the material barrel (1) through a through hole, wherein all the spiral tubes (20) are uniformly arranged along the circumferential direction, and the bottom end of the material barrel (1) is coaxially connected with a center rod (31), a fixing frame (22) is provided on the outside of the spiral tube (20), and a plurality of groups of magnetic bead frames (21) are provided on the fixing frame (22) and the center rod (31), wherein the spacing between each group of magnetic bead frames (21) is equal to the pitch of the spiral tube (20), separation magnetic beads are provided on the inside of the magnetic bead frame (21), and the inside of the magnetic bead frame (21) is in contact with the outside of the spiral tube (20).

2. The circulating tumor cell separation device according to claim 1, characterized in that: The bottom end of the central rod (31) is coaxially connected to a connecting plate (9), and a plurality of liquid guide holes (5) are provided on the connecting plate (9). Each of the liquid guide holes (5) is connected to the bottom end of one of the spiral tubes (20), and the bottom end of the connecting plate (9) is connected to a liquid guide cover (10).

3. The circulating tumor cell step-by-step separation device according to claim 2, characterized in that: The bottom end of the fixing frame (22) is rotatably clamped with a cover body (6), and the liquid-conducting cover (10) is rotatably clamped in the cover body (6). The circumferential angle of the bottom surface of the liquid-conducting cover (10) is one hundred and twenty degrees.

4. The circulating tumor cell step-by-step separation device according to claim 3, characterized in that: An orientation assembly is provided between the fixing frame (22) and the cover body (6), the orientation assembly comprising an orientation plate (23) provided on the outside of any of the fixing frames (22), three sliding plates (26) provided on the outside of the cover body (6), a positioning fork (24) provided on the top of the sliding plate (26), and the orientation plate (23) clamped on the top of the positioning fork (24).

5. The circulating tumor cell step-by-step separation device according to claim 4, characterized in that: Three groups of guide plates (25) are provided on the outside of the cover body (6), and each of the directional plates (23) is slidably clamped between a group of the guide plates (25). An elastic ring (27) is slidably clamped on the outside of the cover body (6), and the inner side of the elastic ring (27) contacts one end of the sliding plate (26).

6. The circulating tumor cell step-by-step separation device according to claim 5, characterized in that: A base (30) is provided at the bottom end of the cover body (6), and three collecting grooves (28) are provided on the inner bottom wall of the base (30). The central angle of each collecting groove (28) is 120 degrees. A clamping plate (29) provided at the bottom end of the cover body (6) is slidably clamped on the outside of the base (30).

7. The circulating tumor cell step-by-step separation device according to claim 6, characterized in that: A switching assembly is provided at the top of the material barrel (1), and the switching assembly includes a support arm (8) provided on the outside of the material barrel (1), the free end of the support arm (8) is connected to a motor (7), the output shaft end of the motor (7) is coaxially connected to a connecting rod (3), the bottom end of the connecting rod (3) is coaxially connected to a fan-shaped plate (4), and the central angle of the fan-shaped plate (4) is 240 degrees.

8. The circulating tumor cell step-by-step separation device according to claim 7, characterized in that: A delay assembly is provided on the inner bottom wall of the material barrel (1), and the delay assembly includes a cover (2) provided on the through hole of the material barrel (1), and the top end of each cover (2) is connected to a plug plate (11) via a moving rod (13).

9. The circulating tumor cell step-by-step separation device according to claim 8, characterized in that: A plurality of fixing frames (16) are provided on the outside of the material barrel (1), an end plate (12) is provided at one end of the insert plate (11), and one end of the inner wall of the fixing frame (16) is connected to one side of the end plate (12) via a spring (17).

10. The circulating tumor cell step-by-step separation device according to claim 9, characterized in that: A top plate (14) is coaxially connected to the connecting rod (3), a directional block (18) is hinged at the free end of the top plate (14), one end of the plug plate (11) is clamped in a directional slot (19) provided at one end of the directional block (18), an electromagnet (15) is provided at the free end of the top plate (14), and magnets are provided at the opposite ends of the directional block (18) and the top plate (14).

Images