Full-automatic circulating tumor cell enrichment device

Abstract

The invention discloses a full-automatic circulating tumor cell enrichment device which comprises a device body placed on a table top, a control panel is fixedly installed on the surface of the front side of the upper end of the device body, a water storage tank is fixedly installed on the inner side of the upper end of the device body, and two conveying water pumps are installed below the water storage tank. A mounting opening is fixedly formed in the lower end of the conveying water pump, an enrichment pipe is arranged below the mounting opening, and a detachable mounting structure is formed between the enrichment pipe and the mounting opening through a threaded structure. According to the full-automatic circulating tumor cell enrichment device, the enrichment pipe is installed at the position of the installation opening through the thread structure, magnetic beads and a blood sample are arranged in the enrichment pipe at the moment, circulating tumor cells in blood are enriched through the magnetic beads, and the internal temperature is detected through a temperature sensor in the enrichment pipe in the process; the conveying air pump and the third connecting pipe are matched to convey air, and the conveyed air is heated by the heater, so that the purpose of keeping the temperature in the enrichment pipe is achieved.

Description

Technical Field

[0001] The present invention relates to the technical field of tumor cell enrichment, and in particular to a fully automatic circulating tumor cell enrichment device. Background Art

[0002] Circulating tumor cells refer to tumor cells that have fallen off from primary tumors or metastatic tumors and entered the blood circulation. These cells can spread to other parts of the body through the blood during the progression and metastasis of the tumor, causing new tumor growth. Since the number of circulating tumor cells in the blood is small, it is not easy to observe. In this case, the tumor cells can be aggregated through an enrichment device to facilitate observation. The most common method is to use immune enrichment to achieve the purpose of enrichment.

[0003] In the prior art, a Chinese patent application numbered CN202411492115.7 discloses a fully automatic circulating tumor cell enrichment device, comprising a chip storage unit, a first reagent storage unit, a second reagent storage unit, a sensing device, a shaking device, and a transfer device; the first reagent storage unit comprises a plurality of cleaning liquid storage boxes and at least one waste liquid storage box; the second reagent storage unit comprises a plurality of test reagent storage racks arranged in sequence; the shaking device is used to fully shake the liquid injected into the chip storage unit and accelerate the reaction; the chip storage unit comprises a structure for storing a positive isolated circulating tumor cell chip; the device realizes the fully automatic capture and staining function of circulating tumor cells in blood samples, has the advantages of easy use and standardized process, can provide standardized sample processing methods for various tumors, such as prostate tumors and colon cancer tumors, and is of great significance to basic research and clinical applications of tumors.

[0004] For example, in the prior art, a Chinese patent application numbered CN202411154975.X discloses a circulating tumor cell reverse enrichment device, which includes an operating table, a frame provided on the operating table, a robotic arm installed on the frame, a sample tank, a reagent tank, a reaction tank and a magnetic separation device provided on the operating table in sequence, and the robotic arm is used to transfer the sample to be tested between the sample tank, the reagent tank, the reaction tank and the magnetic separation device. By using immunomagnetic bead reverse enrichment technology, various types of more diverse CTCs are retained to the maximum extent, including those that may lose traditional markers due to phenotypic conversion and CTCs with low EpCAM expression, thereby improving the efficiency and accuracy of CTC capture, providing a more powerful tool for early diagnosis, treatment monitoring and prognosis evaluation of cancer, and truly meeting clinical needs.

[0005] For example, in the prior art, Chinese patent application number CN201310200385.1 discloses a method for enriching and analyzing circulating tumor cells. This method primarily comprises: subjecting a biological fluid sample to erythrocyte lysis; adding immune microbeads that specifically bind to white blood cells, red blood cells, and / or platelets for incubation; and filtering the cell suspension through a membrane to enrich circulating tumor cells. This integration and optimization of the red blood cell lysis, immune microbead, and membrane methods for enriching CTCs significantly improves the enrichment of circulating tumor cells. This technology achieves a leukocyte removal efficiency of >99.9% and a tumor cell enrichment efficiency of >80%. The present invention also provides a kit for using the aforementioned circulating tumor cell enrichment method, as well as a device for enriching circulating tumor cells.

[0006] Based on the above materials, it can be seen that there are many methods for enriching circulating tumor cells in the existing technology. For the immune enrichment method (that is, using specific antibodies to bind to antigens on the surface of CTCs, and then separating the bound cells from the rest of the blood cells using magnetic beads), temperature control is more important during the use of the immune enrichment method because it requires long-term attachment. Summary of the Invention

[0007] The object of the present invention is to provide a fully automatic circulating tumor cell enrichment device to solve the problem of inconvenient temperature control during the enrichment process mentioned in the above background technology.

[0008] To achieve the above-mentioned objectives, the present invention provides the following technical solutions: a fully automatic circulating tumor cell enrichment device, comprising a device body placed on a desktop, a control panel fixedly installed on the front surface of the upper end of the device body, a water tank fixedly installed on the inner side of the upper end of the device body, and two water delivery pumps are installed below the water storage tank, and a mounting port is fixedly installed on the lower end of the water delivery pump, an enrichment tube is provided below the mounting port, and a disassembly and installation structure is formed between the enrichment tube and the mounting port using a threaded structure; a support frame with an annular structure is installed at the middle position of the inner side of the device body, and the support frame is fixedly connected to the device body by a fixing rod, and electromagnets arranged at equal intervals are fixedly installed on the inner surface of the support frame, and an insulation mechanism for heating the enrichment tube is provided on the inner side of the support frame; a discharge pipe is fixedly installed on the lower surface of the enrichment tube; two supporting turntables are rotatably installed on the inner lower end of the device body, and a collection tank for collecting enriched liquid is placed above the supporting turntable.

[0009] Preferably, a second connecting pipe is fixedly installed at the interface position of the lower end of the water delivery pump, and the second connecting pipe is set to a hollow telescopic structure, and an extraction head is fixedly installed at the bottom end of the second connecting pipe, and a foam buoyancy block is fixedly installed on the outer surface of the lower end of the second connecting pipe.

[0010] Preferably, a first connecting pipe is fixedly installed on the side interface of the water delivery pump, and the bottom end of the first connecting pipe is communicated with the waste liquid tank, and the waste liquid tank is fixedly installed on the inner side of the device body.

[0011] Preferably, the heat preservation mechanism includes an air outlet opened on the inner side of the support frame and a third connecting pipe fixedly installed on the upper surface of the support frame, and the air outlet and the third connecting pipe are connected to each other.

[0012] Preferably, the upper end of the third connecting pipe is communicated with the air delivery pump fixedly installed on the inner side of the device body, and a heater is provided in the middle of the third connecting pipe, and the heater communicates with the temperature sensor fixedly installed inside the enrichment tube.

[0013] Preferably, a positioning clip is fixedly mounted on the upper surface of the carrying turntable, and a snap-fit structure is formed between the collecting tank and the positioning clip.

[0014] Preferably, a driven gear is fixedly mounted on the outer surface of the carrying turntable, and a driving gear is meshedly connected to the side surface of the driven gear, and the driven gear is driven to rotate by a motor fixedly mounted inside the device body.

[0015] Preferably, the water storage tank is connected to the water delivery pump via a delivery pipe fixedly mounted on the surface of the water storage tank, and a limiting slide groove is provided on the upper surface of the water delivery pump.

[0016] Preferably, the limiting slide groove and the guide slide form a left-right sliding structure, and the guide slide is fixedly installed in the middle position of the lower surface of the water tank.

[0017] Preferably, a telescopic cylinder is fixedly installed in the middle position of the lower surface of the guide slide, and the telescopic cylinder is configured as a double-head structure, and the two telescopic ends of the telescopic cylinder are fixedly installed to the water delivery pump.

[0018] Compared with the prior art, the present invention has the following beneficial effects: the fully automatic circulating tumor cell enrichment device adopts a novel structural design, and its specific contents are as follows: 1. Install the enrichment tube to the installation port using the threaded structure. Magnetic beads and blood samples are now loaded into the enrichment tube. Circulating tumor cells in the blood are enriched using the magnetic beads. During this process, the internal temperature is detected by a temperature sensor in the enrichment tube. Air is delivered through an air pump and a third connecting tube. The delivered air is heated by a heater to maintain the internal temperature of the enrichment tube. Furthermore, after the enrichment is completed, the electromagnet inside the support frame is turned on to generate magnetism, thereby adsorbing the magnetic beads inside the enrichment tube under the magnetic effect, so that the magnetic beads stick to the inside of the enrichment tube, and then the suspension inside the enrichment tube can be discharged, thereby increasing the concentration of tumor cells; Furthermore, the suspension in the enrichment tube is discharged through the water delivery pump and the second connecting tube. Since the second connecting tube is a hollow telescopic structure, combined with the buoyancy block outside the bottom end of the second connecting tube, the extraction head can be kept at the upper end of the page, which can better extract the suspension. The extracted suspension is discharged into the waste liquid tank through the first connecting tube.

[0019] 2. A collection tank is installed above the carrying turntable using a positioning clip. The enriched circulating tumor cells and blood samples are discharged into the collection tank through a discharge tube. The motor inside the device body drives the driving gear to rotate, and the meshing action between the driving gear and the driven gear drives the carrying turntable to rotate, achieving continuous operation.

[0020] 3. During the enrichment process, open the telescopic cylinder and use it to push the water delivery pump, so that the water delivery pump uses the limit slide above it to slide on the guide slide, thereby shaking the enrichment tube, making the magnetic beads in the enrichment tube as evenly dispersed as possible, achieving better enrichment effect, and the clean water in the water storage tank is discharged into the enrichment tube through the delivery pipe and the water delivery pump to achieve the purpose of cleaning. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 It is a schematic diagram of the overall structure of the present invention; Figure 2 This is a schematic diagram of the structure of the enrichment tube of the present invention; Figure 3 This is a schematic diagram of the lower surface structure of the water delivery pump of the present invention; Figure 4 For the present invention Figure 3 A in the middle is an enlarged structural diagram; Figure 5 Schematic diagram of the internal structure of the enrichment tube of the present invention; Figure 6 This is a schematic diagram of the internal structure of the support frame of the present invention; Figure 7 For the present invention Figure 6 The enlarged structural diagram at B in the middle; Figure 8 This is a schematic diagram of the structure of the load-bearing turntable of the present invention; Figure 9 This is a schematic diagram of the lower surface structure of the water storage tank of the present invention; Figure 10 This is a schematic diagram of the limiting slide structure of the present invention.

[0022] In the figure: 1. Device body; 2. Control panel; 3. Water storage tank; 301. Delivery pipe; 4. Water delivery pump; 5. Installation port; 6. Enrichment pipe; 601. Discharge pipe; 7. Support frame; 8. Fixing rod; 9. Carrying turntable; 10. Collection tank; 11. Waste liquid tank; 12. First connecting pipe; 13. Second connecting pipe; 14. Extraction head; 15. Buoyancy block; 16. Positioning clamp; 17. Driven gear; 18. Driving gear; 19. Electromagnet; 20. Air outlet; 21. Third connecting pipe; 22. Delivery air pump; 23. Heater; 24. Temperature sensor; 25. Guide slide; 26. Limiting slide; 27. Telescopic cylinder. DETAILED DESCRIPTION

[0023] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0024] Example 1: Please refer to Figure 1-Figure 5 In order to achieve the purpose of enriching circulating tumor cells in the blood, this embodiment provides the following technical solutions, which specifically disclose: a device body 1 is placed on a desktop, a control panel 2 is fixedly installed on the front surface of the upper end of the device body 1, a water storage tank 3 is fixedly installed on the inner side of the upper end of the device body 1, and two water delivery pumps 4 are installed below the water storage tank 3, and a mounting port 5 is fixedly installed on the lower end of the water delivery pump 4, an enrichment tube 6 is provided below the mounting port 5, and a threaded structure is used between the enrichment tube 6 and the mounting port 5 to form a disassembly and installation structure; a support frame 7 with an annular structure is installed in the middle position of the inner side of the device body 1, and the support frame 7 is connected to the device body by a fixing rod 8. The bodies 1 are fixedly connected, and the inner surface of the support frame 7 is fixedly mounted with electromagnets 19 arranged at equal intervals, the lower surface of the enrichment pipe 6 is fixedly mounted with a discharge pipe 601, the lower end interface of the water delivery pump 4 is fixedly mounted with a second connecting pipe 13, and the second connecting pipe 13 is configured as a hollow telescopic structure, and the bottom end of the second connecting pipe 13 is fixedly mounted with an extraction head 14, and the outer surface of the lower end of the second connecting pipe 13 is fixedly mounted with a foam buoyancy block 15, a side interface of the water delivery pump 4 is fixedly mounted with a first connecting pipe 12, and the bottom end of the first connecting pipe 12 is connected to the waste liquid tank 11, and the waste liquid tank 11 is fixedly mounted on the inner side of the device body 1.

[0025] When using the device, the removed blood sample together with the magnetic beads is first placed in the enrichment tube 6, and then the enrichment tube 6 is installed under the water delivery pump 4 using a threaded structure, and the immune cells on the magnetic beads are used to phagocytize tumor cells to achieve the purpose of enrichment. After the enrichment is completed, the electromagnet 19 inside the support frame 7 is turned on first to make the electromagnet 19 generate magnetism, and the magnetic beads inside the enrichment tube 6 are adsorbed by the magnetic effect. The magnetic beads stick to the inner wall of the enrichment tube 6 and the water delivery pump 4 is turned on. The negative pressure of the water delivery pump 4 is used to extract the suspension in the enrichment tube 6 through the second connecting tube 13 (in this process, the buoyancy block 15 outside the lower end of the second connecting tube 13 is used to provide buoyancy. The second connecting tube 13 is a hollow telescopic structure, so that the extraction head 14 remains above the liquid surface). The extracted suspension is transported to the waste liquid tank 11 for storage through the first connecting tube 12.

[0026] Example 2: Please refer to Figure 6-Figure 7 In order to achieve the purpose of heat preservation during the enrichment process, this embodiment provides the following technical solutions, which specifically disclose: a heat preservation mechanism for heating the enrichment tube 6 is provided on the inner side of the support frame 7; the heat preservation mechanism includes an air outlet 20 opened on the inner side of the support frame 7 and a third connecting pipe 21 fixedly installed on the upper surface of the support frame 7, and the air outlet 20 and the third connecting pipe 21 are connected to each other, and the upper end of the third connecting pipe 21 is connected to the delivery air pump 22 fixedly installed on the inner side of the device body 1, and a heater 23 is provided in the middle position of the third connecting pipe 21, and the heater 23 communicates with a temperature sensor 24 fixedly installed inside the enrichment tube 6.

[0027] During the enrichment process, the temperature is monitored in real time by the temperature sensor 24 inside the enrichment tube 6. The monitored temperature data is transmitted to the heater 23. At the same time, the delivery air pump 22 is turned on to draw ambient air into the third connecting tube 21. The air is heated by the heater 23 and then discharged through the air outlet 20, thereby heating the enrichment tube 6, thereby maintaining the internal temperature of the enrichment tube 6 and maintaining cell activity.

[0028] Example 3: Please refer to Figures 8-10In order to achieve the purpose of improving the enrichment effect, this embodiment provides the following technical solutions, which specifically disclose: two supporting turntables 9 are rotatably installed at the lower end of the inner side of the device body 1, and a collection tank 10 for collecting the enriched liquid is placed above the supporting turntable 9. A positioning clamp 16 is fixedly installed on the upper surface of the supporting turntable 9, and a clamping structure is formed between the collection tank 10 and the positioning clamp 16. A driven gear 17 is fixedly installed on the outer surface of the supporting turntable 9, and the side of the driven gear 17 is meshed with a driving gear 18, and the driven gear 17 is fixedly installed on the device. The motor inside the main body 1 drives the rotation, and the water tank 3 is connected to the water delivery pump 4 through the delivery pipe 301 fixedly installed on its surface, and a limiting slide 26 is provided on the upper surface of the water delivery pump 4. The limiting slide 26 and the guide slide 25 form a left and right sliding structure, and the guide slide 25 is fixedly installed in the middle position of the lower surface of the water tank 3. A telescopic cylinder 27 is fixedly installed in the middle position of the lower surface of the guide slide 25, and the telescopic cylinder 27 is set to a double-head structure, and the two telescopic ends of the telescopic cylinder 27 are fixedly installed on the water delivery pump 4.

[0029] At the beginning of enrichment, the telescopic cylinder 27 is turned on and the water delivery pump 4 is pushed by the telescopic cylinder 27. At this time, the water delivery pump 4 slides outside the guide slide 25 through the limiting slide 26 provided on the top of the water delivery pump 4, thereby using the water delivery pump 4 to drive the enrichment tube 6 to shake, thereby causing the magnetic beads in the enrichment tube 6 to shake. In this way, the magnetic beads will be more evenly distributed, and a better enrichment effect will be achieved subsequently. After the enrichment is completed and the suspension is extracted, the discharge pipe 601 at the lower end of the enrichment tube 6 is opened, so that the magnetic beads containing tumor cells are discharged into the collection tank 10 above the carrying turntable 9. After one collection tank 10 is collected, the motor inside the device body 1 is turned on, and the motor drives the driving gear 18 to rotate, so that the driven gear 17 meshing with the driving gear 18 drives the carrying turntable 9 to rotate, achieving the purpose of automatically switching the collection tank 10. After all the water is discharged, the water delivery pump 4 is turned on again, so that the water delivery pump 4 cooperates with the delivery pipe 301 to discharge the clean water in the water storage tank 3 from the second connecting pipe 13, thereby achieving the purpose of flushing the enrichment tube 6.

[0030] In the description of the present invention, unless otherwise specified, "plurality" means two or more; terms such as "upper," "lower," "left," "right," "inner," "outer," "front end," "rear end," "head," and "tail" indicate positions or relationships based on those shown in the accompanying drawings. These terms are intended solely to facilitate the description of the present invention and simplify the description. They do not indicate or imply that the devices or components referred to must have a specific orientation, be constructed, or operate in a specific orientation. Therefore, they should not be construed as limiting the present invention. Furthermore, terms such as "first," "second," and "third" are used for descriptive purposes only and should not be construed as indicating or implying relative importance.

[0031] While embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions, and variations may be made to these embodiments without departing from the principles and spirit of the invention, and that the scope of the invention is defined by the appended claims and their equivalents.

Claims

1. A fully automatic circulating tumor cell enrichment device, comprising a device body (1) placed on a table, a control panel (2) fixedly mounted on the front surface of the upper end of the device body (1), characterized in that: Also includes: A water storage tank (3) is fixedly mounted on the inner side of the upper end of the device body (1), and two water delivery pumps (4) are mounted below the water storage tank (3), and a mounting port (5) is fixedly mounted on the lower end of the water delivery pump (4), an enrichment pipe (6) is arranged below the mounting port (5), and a threaded structure is formed between the enrichment pipe (6) and the mounting port (5); A support frame (7) having an annular structure is installed in the middle position of the inner side of the device body (1), and the support frame (7) is fixedly connected to the device body (1) by a fixing rod (8), and electromagnets (19) arranged at equal intervals are fixedly installed on the inner surface of the support frame (7), and a heat preservation mechanism for heating the enrichment tube (6) is provided on the inner side of the support frame (7); A discharge pipe (601) is fixedly mounted on the lower surface of the enrichment pipe (6); Two supporting turntables (9) are rotatably mounted on the lower inner end of the device body (1), and a collecting tank (10) for collecting the enriched liquid is placed above the supporting turntables (9).

2. The fully automatic circulating tumor cell enrichment device according to claim 1, characterized in that: A second connecting pipe (13) is fixedly mounted at the interface position at the lower end of the water delivery pump (4), and the second connecting pipe (13) is configured as a hollow telescopic structure. An extraction head (14) is fixedly mounted at the bottom end of the second connecting pipe (13), and a foam buoyancy block (15) is fixedly mounted on the outer surface of the lower end of the second connecting pipe (13).

3. The fully automatic circulating tumor cell enrichment device according to claim 2, characterized in that: A first connecting pipe (12) is fixedly installed on the side interface of the water delivery pump (4), and the bottom end of the first connecting pipe (12) is communicated with the waste liquid tank (11), and the waste liquid tank (11) is fixedly installed on the inside of the device body (1).

4. The fully automatic circulating tumor cell enrichment device according to claim 1, characterized in that: The heat preservation mechanism comprises an air outlet (20) provided on the inner side of the support frame (7) and a third connecting pipe (21) fixedly mounted on the upper surface of the support frame (7), and the air outlet (20) and the third connecting pipe (21) are in communication with each other.

5. The fully automatic circulating tumor cell enrichment device according to claim 4, characterized in that: The upper end of the third connecting pipe (21) is in communication with a delivery air pump (22) fixedly mounted on the inner side of the device body (1), and a heater (23) is provided in the middle of the third connecting pipe (21), and the heater (23) communicates with a temperature sensor (24) fixedly mounted on the inside of the enrichment pipe (6).

6. The fully automatic circulating tumor cell enrichment device according to claim 1, characterized in that: A positioning clamp (16) is fixedly mounted on the upper surface of the carrying turntable (9), and a snap-fit structure is formed between the collecting tank (10) and the positioning clamp (16).

7. The fully automatic circulating tumor cell enrichment device according to claim 6, characterized in that: A driven gear (17) is fixedly mounted on the outer surface of the carrying turntable (9), and a driving gear (18) is meshedly connected to the side of the driven gear (17), and the driven gear (17) is driven to rotate by a motor fixedly mounted inside the device body (1).

8. The fully automatic circulating tumor cell enrichment device according to claim 1, characterized in that: The water storage tank (3) is in communication with the water delivery pump (4) via a delivery pipe (301) fixedly mounted on the surface of the water storage tank (3), and a limiting sliding groove (26) is provided on the upper surface of the water delivery pump (4).

9. The fully automatic circulating tumor cell enrichment device according to claim 8, characterized in that: The limiting slide groove (26) and the guide slide (25) form a left-right sliding structure, and the guide slide (25) is fixedly installed at the middle position of the lower surface of the water storage tank (3).

10. The fully automatic circulating tumor cell enrichment device according to claim 9, characterized in that: A telescopic cylinder (27) is fixedly mounted at the middle position of the lower surface of the guide slide (25), and the telescopic cylinder (27) is configured as a double-head structure, and the two telescopic ends of the telescopic cylinder (27) are fixedly mounted to the water delivery pump (4).

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