A multifunctional integrated cervical cancer screening device and screening method

Abstract

This application relates to the technical field of cervical cancer screening medical devices. To integrate multiple screening methods, it provides a multifunctional integrated cervical cancer screening device and method, including a test tube holder, a tube removal and extraction mechanism, a constant temperature incubation chamber, a multi-channel liquid dispensing device, a micro-liquid dispensing device, and a peristaltic pump module. The test tube holder and the micro-liquid dispensing device are located on opposite sides of the constant temperature incubation chamber, while the tube removal and extraction mechanism, the multi-channel liquid dispensing device, and the peristaltic pump module are fixed to the upper end of the chamber. The test tube holder is used to fix test tubes containing cell fluid; the constant temperature incubation chamber is used to fix multiple glass slides; the tube removal and extraction mechanism is used to mix buffer solution with the cell fluid in the test tubes to form a cell suspension and extract it onto the glass slides; the multi-channel liquid dispensing device is used to add Papanicolaou staining reagents onto the glass slides; the micro-liquid dispensing device is used to add P16 immunocytochemical staining reagents onto the glass slides; and the peristaltic pump module is used to add other reagents.

Description

Technical Field

[0001] The present application relates to the technical field of cervical cancer screening medical equipment, and in particular to a multifunctional integrated cervical cancer screening equipment and screening method. Background Art

[0002] Traditional cervical cancer screening methods mainly include cytology and HPV testing. As the main means of screening cervical precancerous lesions and cervical cancer, cytology has its own advantages of strong specificity after years of clinical practice, but it also has many disadvantages. For example: low sensitivity (easy to diagnose), poor repeatability, and greater subjective influence of doctors; at the same time, if cytology is performed alone, it is not clear whether atypical squamous epithelial cells (ACS-US) are diseased cells, and it is difficult to distinguish whether glandular cells are diseased. Conventional immunocytochemical staining also has many common technical problems, such as nonspecific cell coloring and unclear staining background.

[0003] Currently, the best screening method for cervical cancer is the combined screening technology of TCT + tumor suppressor protein P16 immune cell staining. However, based on economic factors and screening efficiency, liquid-based cytology is still an important method for cervical cancer screening. Currently, similar medical instruments mainly realize a single TCT preparation + Papanicolaou staining function, or a single P16 immune cell staining function, and cannot combine the two technologies. If these two screening methods are to be applied at the same time, multiple instruments need to cooperate with each other to achieve it. Whether from an economic perspective or screening efficiency, it cannot meet the current busy clinical testing needs. Summary of the invention

[0004] In order to achieve the integration of multiple screening methods, improve screening efficiency and reduce screening costs, this application provides a multifunctional integrated cervical cancer screening device and screening method. The following technical solutions are adopted:

[0005] A multifunctional integrated cervical cancer screening device, comprising a test tube holder, a tube taking and withdrawing mechanism, a constant temperature incubation chamber, a multi-channel liquid adding device, a micro-liquid adding device and a peristaltic pump module;

[0006] The test tube holder and the micro-liquid adding device are respectively located on both sides of the constant temperature incubation chamber, and the tube taking and withdrawing mechanism, the multi-channel liquid adding device and the peristaltic pump module are fixed on the upper end of the constant temperature incubation chamber;

[0007] The test tube holder is used to fix the test tube containing the cell fluid;

[0008] The constant temperature incubation chamber is used to fix a plurality of glass slides;

[0009] The tube taking and withdrawing mechanism is used to mix the buffer solution with the cell fluid in the test tube to form a cell suspension and extract it onto a glass slide;

[0010] The multi-channel liquid adding device is used to drop the corresponding reagent of Papanicolaou staining onto the glass slide;

[0011] The micro-liquid adding device is used to drop the corresponding reagent of P16 immunocytochemical staining onto the slide;

[0012] The peristaltic pump module is used for dripping other reagents.

[0013] Preferably, the constant temperature incubation chamber comprises a cover plate, a first turntable and a tray which are sequentially arranged along the axial direction, and the first turntable rotates relative to the cover plate and the tray;

[0014] The tray is provided with a drainage hole, and the first turntable is evenly provided with a plurality of slide fixing holes for fixing the slides along the circumferential direction;

[0015] The cover plate and the tray are respectively provided with electric heating wires on one side facing the first rotating disk.

[0016] Preferably, the cover plate is provided with a first liquid adding hole, a second liquid adding hole and a plurality of third liquid adding holes along the circumference, and the liquid adding holes and the slide fixing hole are located on the same circumference;

[0017] The first liquid adding hole is used for adding liquid to the multi-channel liquid adding device, the second liquid adding hole is used for adding liquid to the micro liquid adding device, and the third liquid adding hole is used for adding liquid to the peristaltic pump module.

[0018] Preferably, the top of the device is provided with left and right linear guides and front and rear linear guides, and the front and rear linear guides are fixed on the left and right linear guides and move horizontally left and right along with the left and right linear guides;

[0019] The tube taking and withdrawing mechanism and the multi-channel liquid adding device are respectively fixed on both sides of the front and rear linear guide rails and move forward and backward along the horizontal direction with the front and rear linear guide rails.

[0020] Preferably, the tube taking and withdrawing mechanism comprises a first motor driving device and a liquid adding tube, and the first motor driving device drives the liquid adding tube to move up and down in a vertical direction;

[0021] The liquid adding tube is used for injecting buffer or aspirating cell suspension.

[0022] Preferably, a pipette tip holder for placing a pipette tip is provided on one side of the test tube holder;

[0023] A suction tip recovery slot is provided on one side of the suction tip holder opposite to the test tube holder;

[0024] The suction tip is mounted on the end of the liquid adding tube and is used for injecting buffer or absorbing cell suspension.

[0025] Preferably, a pipette tip baffle and a pipette tip sensor are provided at the bottom end of the pipette removal and withdrawal mechanism, and the liquid adding pipette and the pipette tip baffle are movably interlaced and cooperated to clamp the pipette tip;

[0026] The tube taking and withdrawing sensor is located below the suction head baffle and is used for sensing the suction head.

[0027] Preferably, the multi-channel liquid adding device comprises a second motor driving device, a second rotating disk and a plurality of liquid adding needles, the second motor driving device drives the second rotating disk to move up and down in a vertical direction, and the second rotating disk can rotate relative to the second motor driving device;

[0028] A plurality of the liquid adding needles are evenly arranged along the circumference on the lower surface of the second rotating disk;

[0029] The liquid adding needle is used for dropping the corresponding reagent of the Papanicolaou staining.

[0030] Preferably, the micro-liquid adding device comprises a third motor driving device, a fourth motor driving device and a micro-liquid adding needle, and the micro-liquid adding needle is used to absorb or drip the P16 immunocytochemical staining reagent;

[0031] The third motor driving device drives the micro-liquid adding needle to move up and down in the vertical direction, and the fourth motor driving device drives the micro-liquid adding needle to rotate in the circumferential direction.

[0032] Preferably, the constant temperature incubation chamber is provided with a placement hole for placing a P16 immunocytochemistry staining reagent bottle and a cleaning hole for cleaning a micro-liquid addition needle.

[0033] Preferably, the peristaltic pump module is provided with a movable guide rail on one side of the device.

[0034] Preferably, the device is provided with a plurality of injection mechanisms, and the plurality of injection mechanisms are respectively connected to the tube taking-out and withdrawing mechanism, the multi-channel liquid adding device and the micro-liquid adding device through pipelines to control the absorption or dripping of the reagent.

[0035] Preferably, the injection mechanism comprises a syringe with a scale and a fifth motor drive device, and the fifth motor drive device drives the guide rod of the syringe to reciprocate.

[0036] A screening method of a multifunctional integrated cervical cancer screening device comprises the following steps:

[0037] In the first step, the glass slides are placed in a constant temperature incubation chamber in sequence for fixation, and the test tube containing the cell fluid is placed on a test tube holder;

[0038] The second step is to extract the buffer solution through the tube withdrawal mechanism and inject the buffer solution into the test tube containing the cell solution so that the buffer solution is evenly mixed with the cell solution to form a cell suspension;

[0039] The third step is to extract the cell suspension in the test tube by the tube taking-out mechanism and sequentially drip it onto the glass slide fixed in the constant temperature incubation chamber;

[0040] In the fourth step, the glass slide with the cell suspension is placed in a constant temperature incubator for a period of time to allow the cells to be adsorbed on the glass slide;

[0041] The fifth step is to drip the fixative onto the glass slide through the peristaltic pump module;

[0042] Step 6: The constant temperature incubation chamber rotates at high speed to shake off the waste liquid from the glass slide to form a sedimented cell preparation on the glass slide;

[0043] Step 7: Add the corresponding reagent of Papanicolaou staining to the glass slide through the multi-channel liquid adding device to stain the sedimented cells;

[0044] In the eighth step, the glass slide with the stained sedimented cells is subjected to constant temperature reaction in a constant temperature incubation chamber for a period of time;

[0045] In the ninth step, the dyeing process is completed by adding the rinse solution through the multi-channel liquid adding device and discarding the waste liquid by high-speed rotation of the constant temperature incubation chamber.

[0046] A screening method of a multifunctional integrated cervical cancer screening device comprises the following steps:

[0047] In the first step, the glass slides are placed in a constant temperature incubation chamber in sequence for fixation, and the test tube containing the cell fluid is placed on a test tube holder;

[0048] The second step is to extract the buffer solution through the tube withdrawal mechanism and inject the buffer solution into the test tube containing the cell solution so that the buffer solution is evenly mixed with the cell solution to form a cell suspension;

[0049] The third step is to extract the cell suspension in the test tube by the tube taking-out mechanism and sequentially drip it onto the glass slide fixed in the constant temperature incubation chamber;

[0050] In the fourth step, the glass slide with the cell suspension is placed in a constant temperature incubator for a period of time to allow the cells to be adsorbed on the glass slide;

[0051] The fifth step is to drip the fixative onto the glass slide through the peristaltic pump module;

[0052] Step 6: The constant temperature incubation chamber rotates at high speed to shake off the waste liquid from the glass slide to form a sedimented cell preparation on the glass slide;

[0053] The seventh step is to use a micro-liquid adding device to drop the corresponding reagent of P16 immunocytochemical staining onto the slide to stain the sedimented cells;

[0054] In the eighth step, other reagents used for P16 immunocytochemical staining are added dropwise to the slide through the peristaltic pump module;

[0055] In the ninth step, the glass slide with the stained sedimented cells is subjected to constant temperature reaction in a constant temperature incubation chamber for a period of time;

[0056] The tenth step is to complete the dyeing process by spinning the constant temperature incubation chamber at high speed to remove the waste liquid.

[0057] In summary, this application has the following beneficial effects:

[0058] 1. The present application adopts a tube-taking and withdrawal mechanism for performing base liquid sedimentation-type slide preparation on the collected female cervical exfoliated epithelial cells, a multi-channel liquid-adding device for Papanicolaou staining of liquid-based cells for cytological examination, and a micro-liquid-adding device for P16 immune cell staining for HPV detection of cervical exfoliated epithelial cells. The three functions of the structure of the present application can be independent of each other to realize their own different screening methods, or they can be combined with each other to realize the most advantageous Papanicolaou staining TCT+tumor suppressor protein P16 immune cell staining combined screening technology in the current clinical application of cervical cancer screening.

[0059] 2. This application uses cell screening in a constant temperature incubation chamber, which can control the internal temperature of the entire incubation chamber to be stable within the range of 37±0.5°C. Under the premise of ensuring that the cytological specificity is not lost, high-level diseased cells are marked by the objective biomarker P16 protein to assist in cell morphology detection, which can improve the overall sensitivity of cervical cancer screening.

[0060] 3. This application can use one device to simultaneously realize the functions of liquid-based cell sedimentation preparation, Papanicolaou staining, and P16 immunocytochemical staining, thereby improving the efficiency of cervical cancer screening and reducing the cost of detection. The screening method proposed in this application can realize the automated operation of liquid-based cytology + HPV detection method. The combination of multiple screening methods can greatly improve the accuracy of cervical cancer screening and reduce the missed diagnosis rate and misdiagnosis rate. BRIEF DESCRIPTION OF THE DRAWINGS

[0061] Figure 1 It is a schematic diagram of the overall structure of this embodiment;

[0062] Figure 2 is a top view of the overall structure of this embodiment;

[0063] Figure 3 Schematic diagram of the constant temperature incubation chamber structure of this embodiment;

[0064] Figure 4 is a schematic structural diagram of the constant temperature incubation bin tray of this embodiment;

[0065] Figure 5 1 is a schematic diagram of the structure of the tube taking and withdrawing mechanism of this embodiment;

[0066] Figure 6 is a schematic structural diagram of the multi-channel liquid adding device of this embodiment;

[0067] Figure 7 Schematic diagram of the structure of the micro-liquid adding device of this embodiment;

[0068] Figure 8 It is a schematic structural diagram of the injection mechanism of this embodiment.

[0069] Explanation of reference numerals: 1. test tube support; 2. tube taking and withdrawing mechanism; 21. first motor drive device; 22. liquid adding tube; 23. suction head baffle; 24. tube taking and withdrawing sensor; 25. suction head; 3. constant temperature incubation chamber; 31. cover plate; 311. first liquid adding hole; 312. second liquid adding hole; 313. third liquid adding hole; 32. first turntable; 33. tray; 331. drainage hole; 34. slide fixing hole; 35. placement hole; 36. cleaning hole; 4. multi-channel liquid adding device; 41. second Motor drive device; 42, second turntable; 43, dosing needle; 44, dosing pipeline; 45, turntable drive motor; 5, micro dosing device; 51, third motor drive device; 52, fourth motor drive device; 53, micro dosing needle; 54, circuit box; 6, peristaltic pump module; 61, moving guide rail; 7, left and right linear guide rails; 8, front and rear linear guide rails; 9, pipette tip holder; 10, recovery tank; 11, injection mechanism; 12, syringe; 13, fifth motor drive device; 14, waste liquid tank. DETAILED DESCRIPTION

[0070] The following is combined with Figure 1 -8 Provide further details of this application.

[0071] The embodiment of the present application discloses a multifunctional integrated cervical cancer screening device, including a test tube holder 1, a pipette holder 9, a recovery tank 10, a waste liquid tank 14, a tube taking and withdrawing mechanism 2, a constant temperature incubation chamber 3, a multi-channel liquid adding device 4, a micro-liquid adding device 5, a peristaltic pump module 6, multiple injection mechanisms 11, a circuit board and a power supply. The whole machine structure is divided into three layers of upper, middle and lower structures. The lower layer is a bottom plate, which is used to install and fix the circuit board and the power supply and the micro-liquid adding device 5. The injection mechanism 11 is fixed on the side wall of the lower layer. The middle layer is an operating platform, which is used to place the constant temperature incubation chamber 3, the test tube holder 1, the recovery tank 10 and the waste liquid tank 14, etc., which is the main operating area of ​​the equipment. The peristaltic pump module 6 is fixed on the side wall of the middle layer. The upper layer is provided with a fixed guide rail for supporting and hanging the tube taking and withdrawing mechanism 2 and the multi-channel liquid adding device 4, etc. The device of the present application is externally connected to a touch screen, and the staff operates through the touch screen to realize the automated operation of the liquid-based cytology examination + HPV detection method.

[0072] like Figure 1 As shown in Figure 2, the use of each device of the present application is as follows: the test tube holder 1 is used to fix the test tube containing the cell fluid; the constant temperature incubation chamber 3 is used to fix multiple glass slides; the tube taking and withdrawing mechanism 2 is used to mix the buffer solution with the cell fluid in the test tube to form a cell suspension and extract it onto the glass slide; the multi-channel liquid adding device 4 is used to drip the corresponding reagent of Papanicolaou staining onto the glass slide; the micro-liquid adding device 5 is used to drip the corresponding reagent of P16 immunocytochemistry staining onto the glass slide; the peristaltic pump module 6 is used to drip other reagents; the pipette tip holder 9 is used to store the disposable pipette tips 25; the recovery tank 10 is used to recover the disposable pipette tips 25 after use; the waste liquid tank 14 is used to recover the waste liquid; multiple injection mechanisms 11 are respectively connected to the tube taking and withdrawing mechanism 2, the multi-channel liquid adding device 4 and the micro-liquid adding device 5 through pipelines and control the absorption or dripping of reagents, and the circuit board and power supply are used to power the equipment.

[0073] like Figure 3 As shown in Figure 4, the constant temperature incubation chamber 3 includes a cover plate 31, a first turntable 32 and a tray 33 which are arranged in sequence along the axial direction. The cover plate 31 and the tray 33 are fixed, and the first turntable 32 can rotate relative to the cover plate 31 and the tray 33. The tray 33 is provided with a drainage hole 331. The waste liquid generated during the operation of the constant temperature incubation chamber 3 is thrown onto the tray 33 through the high-speed rotation of the first turntable 32, and the waste liquid is discharged through the drainage hole 331 of the tray 33. The drainage hole 331 is connected to the waste liquid tank 14 through a pipeline, and the waste liquid is discharged into the waste liquid tank 14 for further treatment.

[0074] The first turntable 32 is evenly provided with a plurality of slide fixing holes 34 for fixing the slides along the circumferential direction. When in use, the slides are placed in the first turntable 32 in the constant temperature incubation chamber 3 in sequence from the starting point. The cover plate 31 is provided with a first liquid adding hole 311, a second liquid adding hole 312 and a plurality of third liquid adding holes 313 along the circumferential direction. The liquid adding holes on the cover plate 31 and the slide fixing holes 34 are on the same circumference. The first liquid adding hole 311 is used for adding liquid to the multi-channel liquid adding device 4. The liquid is added through the first liquid adding hole 311 is used to add the reagent corresponding to the Papanicolaou staining onto the glass slide, the second liquid adding hole 312 is used for the micro-liquid adding device 5 to add liquid, and the reagent corresponding to the P16 immunocytochemistry staining is added onto the glass slide through the second liquid adding hole 312, and the third liquid adding hole 313 is used for the peristaltic pump module 6 to add liquid. Other reagents can be added through the third liquid adding hole 313. By rotating the first turntable 32, the glass slide can be rotated to different liquid adding holes to add reagents to meet the needs of various screening tests.

[0075] The constant temperature incubation chamber 3 is the core structure of the present device. Liquid-based cell sedimentation preparation, its preparation and Papanicolaou staining or its preparation and P16 immunocytochemical staining are all carried out in the constant temperature incubation chamber 3. Therefore, higher requirements are placed on the temperature of the constant temperature incubation chamber 3. During the reagent reaction, the temperature of the constant temperature incubation chamber 3 needs to be controlled within the range of 37±0.5°C. The present application provides electric heating wires (not marked in the figure) on the cover plate 31 and the tray 33 of the constant temperature incubation chamber 3, respectively, on the side facing the first turntable 32 to keep the entire constant temperature incubation chamber 3 warm. A temperature control module is provided in the constant temperature incubation chamber 3. During the reagent dripping and reagent reaction, the temperature control module of the constant temperature incubation chamber 3 starts to work to control the internal temperature of the entire incubation chamber to be stable, thereby improving the accuracy of cervical cancer screening and reducing the missed diagnosis rate and the misdiagnosis rate.

[0076] like Figure 2 As shown, the upper guide rails of the equipment are divided into left and right linear guide rails 7 and front and rear linear guide rails 8. The front and rear linear guide rails 8 are fixed on the left and right linear guide rails 7 and move horizontally left and right with the left and right linear guide rails 7. The pipe withdrawal mechanism 2 and the multi-channel liquid adding device 4 are respectively fixed on both sides of the front and rear linear guide rails 8 and move horizontally forward and backward with the front and rear linear guide rails 8.

[0077] like Figure 5 As shown, the tube taking and withdrawing mechanism 2 includes a first motor driving device 21, a liquid adding tube 22, a pipette tip baffle 23 and a tube taking and withdrawing sensor 24. The first motor driving device 21 drives the liquid adding tube 22 to move up and down in the vertical direction. The liquid adding tube 22 is used to inject buffer or absorb cell suspension. The liquid adding tube 22 and the pipette tip baffle 23 are movably interlaced and cooperated to clamp off the pipette tip 25. The tube taking and withdrawing sensor 24 is located below the pipette tip baffle 23 and is used to sense the pipette tip 25.

[0078] like Figure 1 As shown in Figure 2, the test tube holder 1 is located on one side of the constant temperature incubation chamber 3, the pipette tip holder 9 is located on one side of the test tube holder 1, the recovery tank 10 is located on the side of the pipette tip holder 9 opposite to the test tube holder 1, and the tube taking and withdrawing mechanism 2 is suspended on the test tube holder 1 and the upper end of the constant temperature incubation chamber 3 through the front and rear linear guide rails 8.

[0079] When the tube taking and withdrawing mechanism 2 is working, it is first driven to move above the tip holder 9 by the left and right linear guides 7 and the front and rear linear guides 8, and the liquid adding tube 22 is driven downward by the first motor driving device 21 and inserted into the tip 25 on the tip holder 9, sucking the disposable tip 25 on the tip holder 9 and taking the disposable tip 25 out of the tip holder 9 by moving upward by the first motor driving device 21; then, it is driven to move above the test tube holder 1 by the left and right linear guides 7 and the front and rear linear guides 8, and the liquid adding tube 22 is driven downward by the first motor driving device 21 and inserted into the test tube with cell fluid on the test tube holder 1, and the buffer solution is injected and mixed with the cell fluid by the injection mechanism 11, and then the liquid adding tube 22 is driven by the first motor driving device 21 to move up and down quickly and continuously, so that the buffer solution and the cell fluid are stirred and mixed evenly to form a cell suspension.

[0080] At this time, the injection mechanism 11 works, absorbs an appropriate amount of cell suspension into the liquid adding tube 22 and moves upward through the first motor drive device 21. The liquid adding tube 22 is driven by the left and right linear guides 7 and the front and rear linear guides 8 to move to the top of the warm incubation chamber, aligns with the first liquid adding hole 311 and moves downward to insert into the first liquid adding hole 311 to drip the cell suspension on the glass slide. After the dripping is completed, the liquid adding tube 22 moves to the top of the disposable tip 25 recovery tank 10. The liquid adding tube 22 moves upward, and the disposable tip baffle 23 will clamp the disposable tip 25 on the bottom of the liquid adding tube 22 and drop it into the recovery tank 10. During the process of taking out or withdrawing the tube, if the tube is not taken out or withdrawn normally, the tube taking and withdrawing sensor 24 will be triggered, and the tube taking and withdrawing operation will be repeated until it is completed. The disposable tip is used to avoid cross contamination of the cell suspension absorption and dripping process, thereby ensuring the accuracy of screening.

[0081] Repeat the above-mentioned dripping process and drip the cell suspension in the test tube onto the corresponding glass slides in turn. During the dripping process, the turntable in the constant temperature incubation chamber 3 will also rotate synchronously, and the glass slides that have not yet been dripped with the cell suspension are aligned with the first liquid addition hole 311 in turn until all the glass slides are dripped with the cell suspension.

[0082] like Figure 6 As shown, the multi-channel liquid adding device 4 is suspended on the test tube holder 1 and the upper end of the constant temperature incubation chamber 3 through the front and rear linear guide rails 8. The multi-channel liquid adding device 4 includes a second motor driving device 41, a second turntable 42, a turntable driving motor 45 and a plurality of liquid adding needles 43. The second motor driving device 41 drives the second turntable 42 to move up and down in the vertical direction, and the turntable driving motor 45 drives the second turntable 42 to rotate relative to the second motor driving device 41; the plurality of liquid adding needles 43 are evenly arranged along the circumference on the lower surface of the second turntable 42, and the liquid adding needles 43 are used to drip the corresponding reagents for Papanicolaou staining, and the reagents stored in each liquid adding needle 43 are different.

[0083] When the multi-channel liquid-adding device 4 is working, it is driven to move above the first liquid-adding hole 311 by the left and right linear guides 7 and the front and rear linear guides 8, and the turntable drive motor 45 drives the second turntable 42 to rotate, and selects the reagent channel that needs to be added with liquid, so that its liquid-adding needle 43 is aligned with the first liquid-adding hole 311, and the second motor drive device 41 drives its liquid-adding needle 43 to move downward and insert into the first liquid-adding hole 311, and the injection mechanism 11 drips the corresponding reagent onto the glass slide through the liquid-adding pipe 44 to complete the liquid-adding operation.

[0084] like Figure 7 As shown, the micro-liquid adding device 5 is located on the side of the constant temperature incubation chamber 3 opposite to the test tube holder 1, and its base is fixed on the bottom plate. The micro-liquid adding device 5 includes a third motor driving device 51, a fourth motor driving device 52, a circuit box 54 and a micro-liquid adding needle 53. The fourth motor driving device 52 is fixed on the third motor driving device 51. The micro-liquid adding needle 53 is located at the upper end of the constant temperature incubation chamber 3 through the third motor driving device 51. The micro-liquid adding needle 53 is used to absorb or drip P16 immunocytochemistry staining reagent. The third motor driving device 51 drives the micro-liquid adding needle 53 to move up and down in the vertical direction, and the fourth motor driving device 52 drives the micro-liquid adding needle 53 to rotate circumferentially.

[0085] like Figure 2 As shown in FIG. 3 , the upper end of the cover plate 31 of the constant temperature incubation chamber 3 is provided with a placement hole 35 for placing a P16 immunocytochemistry staining reagent bottle and a cleaning hole 36 for cleaning the micro-liquid addition needle 53, and the circuit box 54 is equipped with a liquid level detection circuit board and a photoelectric switch for realizing liquid level detection in the reagent tube.

[0086] When the micro-liquid adding device 5 is working, the green indicator light on the circuit board lights up when the reagent is detected, and the photoelectric switch cooperates with the third motor drive device 51 to control the up and down movement of the micro-liquid adding needle 53, and the micro-liquid adding needle 53 is inserted into the reagent tube on the cover plate 31. At this time, the injection mechanism 11 works to draw the reagent from the reagent tube into the pipeline, and then the fourth motor drive device 52 controls the micro-liquid adding needle 53 to rotate and align it with the second liquid adding hole 312 on the cover plate 31. Then the third motor drive device 51 controls the micro-liquid adding needle 53 to move downward to a certain position, close to the glass slide on the first turntable 32, and the injection mechanism 11 works to drip the reagent onto the glass slide.

[0087] After the reagent is added, the detection circuit board controls the micro-liquid addition needle 53 to move upward and rotate to the cleaning hole 36, and the injection mechanism 11 injects clean water to clean the micro-liquid addition needle 53. There are four types of P16 immunocytochemical staining reagents. When performing liquid-based cell preparation and P16 immunocytochemical staining functions, they are added one by one to the slide. After adding one reagent, in order to avoid cross-contamination of reagents, the micro-liquid addition needle 53 needs to move to the cleaning hole 36 on the cover plate 31, and the micro-liquid addition needle 53 is cleaned by injecting purified water. After cleaning, the addition of other reagents is completed in sequence according to the above operations.

[0088] like Figure 1 As shown in FIG. 2 , the peristaltic pump module 6 is provided with a movable guide rail 61 on the side wall of the middle layer of the device, and can be moved left and right in the horizontal direction through the movable guide rail 61. If other reagents need to be added, the peristaltic pump module 6 is moved to the third liquid adding hole 313 for dripping through the movable guide rail 61.

[0089] like Figure 8 As shown, the injection mechanism 11 includes a syringe 12 with a scale and a fifth motor drive device 13. The fifth motor drive device 13 drives the guide rod of the syringe 12 to reciprocate. The function of the syringe 12 is to add the staining reagent on the one hand and to withdraw the reagent from the pipeline on the other hand.

[0090] After the equipment has completed the relevant operations, the injection mechanism 11 recovers the reagent from the pipeline, and then the withdrawal mechanism 2 and the multi-channel liquid adding device 4 are moved to the waste liquid tank 14, all the pipelines are injected with clean water, the pipelines are cleaned, the middle workbench is tidied, the cleaning work is completed, and the power is turned off to complete all operations of the equipment.

[0091] A screening method of a multifunctional integrated cervical cancer screening device, when liquid-based cell preparation and Pap staining functions are selected, includes the following steps:

[0092] In the first step, the glass slides are sequentially placed in the constant temperature incubation chamber 3 for constant fixation, and the test tube containing the cell fluid is placed on the test tube holder 1; in the second step, the buffer solution is extracted by the tube withdrawal mechanism 2 and injected into the test tube containing the cell fluid so that the buffer solution is evenly mixed with the cell fluid to form a cell suspension; in the third step, the cell suspension in the test tube is extracted by the tube withdrawal mechanism 2 and sequentially dripped onto the glass slide fixed in the constant temperature incubation chamber 3; in the fourth step, the glass slide with the cell suspension is placed in the constant temperature incubation chamber 3 for a period of time to allow the cells to be adsorbed on the glass slide; In the fifth step, the fixing liquid is dripped onto the glass slide through the peristaltic pump module 6; in the sixth step, the constant temperature incubation chamber 3 is rotated at a high speed to shake off the waste liquid from the glass slide to form a sedimentation cell preparation on the glass slide; in the seventh step, the corresponding reagent for Papanicolaou staining is dripped onto the glass slide through the multi-channel liquid adding device 4 to stain the sedimentation cells; in the eighth step, the glass slide with the stained sedimentation cells is subjected to constant temperature reaction in the constant temperature incubation chamber 3 for a period of time; in the ninth step, the flushing liquid is added through the multi-channel liquid adding device 4 and the waste liquid is shaken off by high-speed rotation of the constant temperature incubation chamber 3 to complete the staining process.

[0093] A screening method of a multifunctional integrated cervical cancer screening device, when liquid-based cell preparation and P16 immunocytochemical staining functions are selected, includes the following steps:

[0094] In the first step, the glass slides are sequentially placed in the constant temperature incubation chamber 3 and fixed, and the test tube containing the cell fluid is placed on the test tube holder 1; in the second step, the buffer solution is extracted by the tube withdrawal mechanism 2 and injected into the test tube containing the cell fluid so that it is evenly mixed with the cell fluid to form a cell suspension; in the third step, the cell suspension in the test tube is extracted by the tube withdrawal mechanism 2 and sequentially dripped onto the glass slide fixed in the constant temperature incubation chamber 3; in the fourth step, the glass slide with the cell suspension is kept at a constant temperature in the constant temperature incubation chamber 3 for a period of time so that the cells are adsorbed on the glass slide; in the fifth step, the peristaltic pump module 6 is used to drip the cell suspension in the test tube. The fixing solution is added to the glass slide; in the sixth step, the constant temperature incubation chamber 3 is rotated at a high speed to shake off the waste liquid from the glass slide to form a sedimentation cell preparation on the glass slide; in the seventh step, the micro-liquid adding device 5 is used to drop the corresponding reagents of P16 immunocytochemistry staining onto the glass slide to stain the sedimentation cells; in the eighth step, other reagents used for P16 immunocytochemistry staining are added to the glass slide through the peristaltic pump module 6; in the ninth step, the glass slide with the stained sedimentation cells is subjected to constant temperature reaction in the constant temperature incubation chamber 3 for a period of time; in the tenth step, the waste liquid is shaken off by high-speed rotation of the constant temperature incubation chamber 3 to complete the staining process.

[0095] The present application provides an instrument operation process and implementation scheme for combining Papanicolaou staining and P16 immunocytochemical staining after liquid-based cell sedimentation preparation. The device and method can first realize liquid-based cell sedimentation preparation. After the preparation operation is completed, the slide can be taken out for other operations, or subsequent Papanicolaou staining for cytological examination, or P16 immunocytochemical staining for HPV detection operation. The two methods are combined with each other. Under the premise of ensuring that the cytological specificity is not lost, high-level diseased cells are marked by the objective biomarker P16 protein to assist in cell morphology detection, which can improve the sensitivity of cervical cancer screening as a whole. Moreover, the negative predictive value of P16 immunocytochemical staining is close to 100%. In the application of cervical cancer screening, it almost does not lead to missed diagnosis. The device and method of the present application can improve the efficiency of cervical cancer screening, reduce the detection cost, and realize the integration and complementarity of multiple screening methods.

[0096] The above are all preferred embodiments of the present application, and the protection scope of the present application is not limited thereto. Therefore, any equivalent changes made according to the structure, shape, and principle of the present application should be included in the protection scope of the present application.

Claims

1. A multifunctional integrated cervical cancer screening device, characterized in that: It includes a test tube holder, a tube taking and withdrawing mechanism, a constant temperature incubation chamber, a multi-channel liquid adding device, a micro-liquid adding device and a peristaltic pump module; The test tube holder and the micro-liquid adding device are respectively located on both sides of the constant temperature incubation chamber, and the tube taking and withdrawing mechanism, the multi-channel liquid adding device and the peristaltic pump module are fixed on the upper end of the constant temperature incubation chamber; The test tube holder is used to fix the test tube containing the cell fluid; The constant temperature incubation chamber is used to fix a plurality of glass slides; The tube taking and withdrawing mechanism is used to mix the buffer solution with the cell fluid in the test tube to form a cell suspension and extract it onto a glass slide; The multi-channel liquid adding device is used to drop the corresponding reagent of Papanicolaou staining onto the glass slide; The micro-liquid adding device is used to drop the corresponding reagent of P16 immunocytochemical staining onto the slide; The peristaltic pump module is used to drip other reagents; The constant temperature incubation chamber comprises a cover plate, a first turntable and a tray which are sequentially arranged along the axial direction, and the first turntable rotates relative to the cover plate and the tray; The tray is provided with a drainage hole, and the first turntable is evenly provided with a plurality of slide fixing holes for fixing the slides along the circumferential direction; The cover plate and the tray are respectively provided with electric heating wires on one side facing the first rotating disk; The cover plate is provided with a first liquid adding hole, a second liquid adding hole and a plurality of third liquid adding holes along the circumference, and the liquid adding holes and the slide fixing holes are on the same circumference; The first liquid adding hole is used for adding liquid to the multi-channel liquid adding device, the second liquid adding hole is used for adding liquid to the micro liquid adding device, and the third liquid adding hole is used for adding liquid to the peristaltic pump module.

2. The multifunctional integrated cervical cancer screening device according to claim 1, characterized in that: The top of the device is provided with left and right linear guide rails and front and rear linear guide rails, and the front and rear linear guide rails are fixed on the left and right linear guide rails and move horizontally left and right along with the left and right linear guide rails; The tube taking and withdrawing mechanism and the multi-channel liquid adding device are respectively fixed on both sides of the front and rear linear guide rails and move forward and backward along the horizontal direction with the front and rear linear guide rails.

3. The multifunctional integrated cervical cancer screening device according to claim 1, characterized in that: The tube taking and withdrawing mechanism comprises a first motor driving device and a liquid adding tube, wherein the first motor driving device drives the liquid adding tube to move up and down in a vertical direction; The liquid adding tube is used for injecting buffer or aspirating cell suspension.

4. The multifunctional integrated cervical cancer screening device according to claim 3, characterized in that: A pipette tip holder for placing a pipette tip is provided on one side of the test tube holder; A suction tip recovery slot is provided on one side of the suction tip holder opposite to the test tube holder; The suction tip is mounted on the end of the liquid adding tube and is used for injecting buffer or absorbing cell suspension.

5. The multifunctional integrated cervical cancer screening device according to claim 4, characterized in that: The bottom end of the tube removal and withdrawal mechanism is provided with a pipette tip baffle and a pipette removal and withdrawal sensor, and the liquid adding tube and the pipette tip baffle are movably interlaced and matched to clamp the pipette tip; The tube taking and withdrawing sensor is located below the suction head baffle and is used for sensing the suction head.

6. The multifunctional integrated cervical cancer screening device according to claim 1, characterized in that: The multi-channel liquid adding device comprises a second motor driving device, a second rotating disk and a plurality of liquid adding needles, wherein the second motor driving device drives the second rotating disk to move up and down in a vertical direction, and the second rotating disk can rotate relative to the second motor driving device; A plurality of the liquid adding needles are evenly arranged along the circumference on the lower surface of the second rotating disk; The liquid adding needle is used for dropping the corresponding reagent of the Papanicolaou staining.

7. The multifunctional integrated cervical cancer screening device according to claim 1, characterized in that: The micro-liquid adding device comprises a third motor driving device, a fourth motor driving device and a micro-liquid adding needle, and the micro-liquid adding needle is used for sucking or dripping P16 immunocytochemical staining reagent; The third motor driving device drives the micro-liquid adding needle to move up and down in the vertical direction, and the fourth motor driving device drives the micro-liquid adding needle to rotate in the circumferential direction.

8. The multifunctional integrated cervical cancer screening device according to claim 7, characterized in that: The constant temperature incubation chamber is provided with a placement hole for placing a P16 immunocytochemistry staining reagent bottle and a cleaning hole for cleaning a micro-liquid addition needle.

9. The multifunctional integrated cervical cancer screening device according to claim 1, characterized in that: The peristaltic pump module is provided with a movable guide rail on one side of the device.

10. The multifunctional integrated cervical cancer screening device according to claim 1, characterized in that: The device is provided with a plurality of injection mechanisms, which are respectively connected with the pipe taking and withdrawing mechanism, the multi-channel liquid adding device and the micro-liquid adding device through pipelines to control the absorption or dripping of the reagent.

11. The multifunctional integrated cervical cancer screening device according to claim 10, characterized in that: The injection mechanism comprises a syringe with a scale and a fifth motor driving device, and the fifth motor driving device drives the guide rod of the syringe to reciprocate.

12. A screening method for cervical cancer using a multifunctional integrated cervical cancer screening device according to any one of claims 1 to 11, characterized in that: The steps include: In the first step, the glass slides are placed in a constant temperature incubation chamber in sequence for fixation, and the test tube containing the cell fluid is placed on a test tube holder; The second step is to extract the buffer solution through the tube withdrawal mechanism and inject the buffer solution into the test tube containing the cell solution so that the buffer solution is evenly mixed with the cell solution to form a cell suspension; The third step is to extract the cell suspension in the test tube by the tube taking-out mechanism and sequentially drip it onto the glass slide fixed in the constant temperature incubation chamber; In the fourth step, the glass slide with the cell suspension is placed in a constant temperature incubator for a period of time to allow the cells to be adsorbed on the glass slide; The fifth step is to drip the fixative onto the glass slide through the peristaltic pump module; Step 6: The constant temperature incubation chamber rotates at high speed to shake off the waste liquid from the glass slide to form a sedimented cell preparation on the glass slide; Step 7: Add the corresponding reagent of Papanicolaou staining to the glass slide through the multi-channel liquid adding device to stain the sedimented cells; In the eighth step, the glass slide with the stained sedimented cells is subjected to constant temperature reaction in a constant temperature incubation chamber for a period of time; In the ninth step, the dyeing process is completed by adding the rinse solution through the multi-channel liquid adding device and discarding the waste liquid by high-speed rotation of the constant temperature incubation chamber.

13. A screening method of a multifunctional integrated cervical cancer screening device according to any one of claims 1 to 11, characterized in that: The steps include: In the first step, the glass slides are placed in a constant temperature incubation chamber in sequence for fixation, and the test tube containing the cell fluid is placed on a test tube holder; The second step is to extract the buffer solution through the tube withdrawal mechanism and inject the buffer solution into the test tube containing the cell solution so that the buffer solution is evenly mixed with the cell solution to form a cell suspension; The third step is to extract the cell suspension in the test tube by the tube taking-out mechanism and sequentially drip it onto the glass slide fixed in the constant temperature incubation chamber; In the fourth step, the glass slide with the cell suspension is placed in a constant temperature incubator for a period of time to allow the cells to be adsorbed on the glass slide; The fifth step is to drip the fixative onto the glass slide through the peristaltic pump module; Step 6: The constant temperature incubation chamber rotates at high speed to shake off the waste liquid from the glass slide to form a sedimented cell preparation on the glass slide; The seventh step is to use a micro-liquid adding device to drop the corresponding reagent of P16 immunocytochemical staining onto the slide to stain the sedimented cells; In the eighth step, other reagents used for P16 immunocytochemical staining are added dropwise to the slide through the peristaltic pump module; In the ninth step, the glass slide with the stained sedimented cells is subjected to constant temperature reaction in a constant temperature incubation chamber for a period of time; The tenth step is to complete the dyeing process by spinning the constant temperature incubation chamber at high speed to remove the waste liquid.

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