Fully automatic liquid-based cell slide making machine
By designing a fully automatic liquid-based cell tableting machine including transport module, cell enrichment module, pipette tip module and production module, the problems of excessive manual participation, complex machine structure and inadequate installation of the gun tip in the prior art are solved, and the liquid-based cell tableting effect with high automation, compact and simple structure and high success rate is achieved.
Patent Information
- Application Number
- CN202411773902.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2024-12-05
- Publication Date
- 2025-04-22
- Estimated Expiration
- 2044-12-05
AI Technical Summary
The existing fully automatic liquid-based cell filmmakers have problems such as excessive manual participation, complex machine structure and inadequate installation of gun tips, resulting in failure in production and difficulty in maintenance.
A fully automatic liquid-based cell tableting machine including a transport module, a cell enrichment module, a pipette head module and a production module is designed to achieve automated operations through a robotic arm and an insufflation mechanism, simplify the mechanical structure, and improve the degree of automation and installation accuracy through self-matching components and photoelectric sensors.
It has achieved a liquid-based cell filmmaker with high automation, compact and simple structure and high success rate, reducing manual participation, simplifying machine maintenance, and improving production reliability and efficiency.
Smart Images

Figure CN119223713B_ABST
Abstract
Description
Technical Field
[0001] The invention relates to the technical field of cell slide making, and in particular to a fully automatic liquid-based cell slide making machine. Background Art
[0002] The existing liquid-based cell preparation technology using the natural sedimentation method includes three steps: centrifugal cell enrichment, sedimentation preparation and cell staining.
[0003] For example, patent CN211784689U provides a fully automatic pathology slide staining machine, including: a main body, a pump group, a centrifuge, a sample slot, a staining slot, a first nozzle placement slot, a second nozzle placement slot, a nozzle liquid collection arm, a dye adding and extracting arm and an arm horizontal movement module, which makes cell preparation and staining operations more convenient and quick, and provides a good hardware equipment foundation for improving work efficiency and accuracy, so as to make the analysis of complex specimens more effective.
[0004] The existing problems are: 1. The centrifugation process requires manual balancing, and there is too much manual involvement, and it cannot be truly fully automatic; 2. Two robotic arms are required to complete the functions of centrifugal supernatant suction and discharge after cell enrichment, sample transfer, reagent addition and waste liquid discharge. The mechanical structure is complex and difficult to maintain.
[0005] In addition, existing fully automatic liquid-based cell slide making machines still have problems such as improper installation of disposable pipette tips leading to slide making failures.
[0006] Therefore, there is an urgent need for a fully automatic liquid-based cell slide making machine with a simple structure to solve the problems of excessive manual participation, complex machine structure and easy failure in slide making. Summary of the invention
[0007] The present invention provides a fully automatic liquid-based cell slice making machine to solve the problems of excessive manual participation, difficult machine maintenance and improper installation of the gun head in the related art.
[0008] To achieve the above object, the present invention provides a fully automatic liquid-based cell slide making machine, comprising: a transport module, a cell enrichment module, a pipette tip module and a slide making module, wherein the cell enrichment module, the pipette tip module and the slide making module are arranged in sequence, the transport module is arranged above the cell enrichment module, the pipette tip module and the slide making module, the transport module comprises a mechanical arm and a liquid suction and injection mechanism, and the liquid suction and injection mechanism is fixedly mounted on the mechanical arm;
[0009] The cell enrichment module comprises: a centrifugal turntable, a first driving device, a waste liquid dumping device and a self-balancing component;
[0010] The outer periphery of the centrifugal turntable is evenly provided with sample bottle bearing seats, both sides of the upper part of the sample bottle bearing seats are connected to the centrifugal turntable shaft, and the sample bottle bearing seats can swing around the shaft;
[0011] The waste liquid dumping device is composed of a sample bottle push rod, and the sample bottle push rod can push the sample bottle supporting seat to make the sample bottle supporting seat swing along the axis.
[0012] Further, it also includes a self-balancing component;
[0013] The self-balancing component includes a detection unit, several balancing blocks and a transfer suction cup. The detection unit detects whether the sample bottles in the centrifugal turntable are balanced and records the sample bottle holders that need to be balanced. The transfer suction cup is fixed on the transfer module, and the transfer suction cup is driven by a robotic arm to absorb the balancing blocks and place them in the sample bottle holders that need to be balanced.
[0014] Further, the robotic arm includes: an X arm, a Y arm and a Z arm;
[0015] The X arm is movably mounted on one side of the film-making module, the Y arm is movably mounted on the X arm, and the Z arm is movably mounted on the Y arm;
[0016] The liquid suction and injection mechanism is fixedly arranged on the Z arm.
[0017] Furthermore, the suction and injection mechanism includes a plurality of suction and injection components, and the suction and injection components include a sleeve and a suction needle and an injection needle inside the sleeve, and the suction needle penetrates the sleeve and extends out.
[0018] Further, the first end of the aspiration needle is connected to the waste liquid bottle through the first waste liquid pipeline, the first waste liquid pipeline is provided with a first pump and a first valve, and the second end of the aspiration needle is bent. The upper end of the injection needle is connected to the reagent bottle through the reagent pipeline, and the reagent pipeline is provided with a second pump and a second valve. A controller is also included, the controller is electrically connected to the first pump and the first valve, and the second pump and the second valve, and the controller controls the switch of the first pump and the first valve, and the second pump and the second valve.
[0019] Furthermore, the suction and injection components are 1-5 groups, which are arranged in a line and installed on the robotic arm.
[0020] Furthermore, the sample bottle push rod includes a horizontal push rod and a vertical push rod, and the horizontal push rod is located above the vertical push rod. The horizontal push rod is located at the upper part of the sample bottle support seat, and includes a first vertical arm, a first horizontal arm and a second driving device. The first vertical arm and the first horizontal arm are connected in a T-shape, the first horizontal arm is perpendicular to the radius of the centrifugal turntable, and the second driving device is connected to the first vertical arm. The vertical push rod is located below the sample bottle support seat, and includes a second vertical arm, a second horizontal arm and a third driving device. The second vertical arm and the second horizontal arm are connected in a T-shape, the second horizontal arm is perpendicular to the radius of the centrifugal turntable, and the third driving device is connected to the second vertical arm; after the horizontal push rod is pushed, it contacts the upper part of the side wall of the sample bottle, and can push the sample bottle in the horizontal direction, so that the sample bottle drives the sample bottle support seat to swing and tilt around the axis; after the vertical push rod is pushed, it contacts the lower part of the side wall of the inclined sample bottle support seat, and can push the sample bottle support seat in the vertical direction, so that the sample bottle support seat drives the sample bottle to continue to swing and tilt around the axis.
[0021] Furthermore, a fixing block is provided in the middle of the second cross arm, and the size of the fixing block is adapted to the distance between the two sample bottle supporting seats.
[0022] Furthermore, it also includes a waste liquid collection device, which includes a waste liquid receiving plate, a second waste liquid pipeline and a waste liquid bottle. The waste liquid receiving plate is arranged below the centrifugal turntable and is in a circular ring shape. The waste liquid receiving plate includes a plate bottom, an inner plate wall and an outer plate wall. The inner plate wall and the outer plate wall are perpendicular to the plate bottom. The inner plate wall is located in a circle around the inner periphery of the plate bottom, and the outer plate wall is located in a circle around the outer periphery of the plate bottom. The plate bottom, the inner plate wall and the outer plate wall together form an annular recessed space. The plate bottom is provided with a waste liquid port that passes through from top to bottom. The waste liquid port is located below the sample bottle push rod. The lower end of the waste liquid port is connected to the waste liquid bottle through the second waste liquid pipeline. A third valve is provided on the pipeline, and the switch of the third valve is controlled by a controller.
[0023] Furthermore, the detection unit includes a positioning sensor and a bottle detection sensor. The positioning sensor includes component one and component two. Component one is fixedly arranged on the centrifugal turntable and rotates with the centrifugal turntable. Component one and component two are used in conjunction with each other to position the sample bottle support seat. The bottle detection sensor is arranged on one side of the centrifugal turntable, slightly higher than the sample bottle support seat. The bottle detection sensor determines whether there is a sample bottle in the sample bottle support seat. The positioning sensor and the bottle detection sensor work together to confirm the sample bottle support seat where the balancing block needs to be placed.
[0024] Furthermore, the balancing block is a columnar structure of the same weight as the sample bottle, with a non-through insertion hole in the middle, and the diameter of the insertion hole is slightly larger than the sleeve of the aspiration and injection component.
[0025] Furthermore, the pipette tip module includes a pipette tip seat and a photoelectric sensor. The pipette tip seat is provided with a pipette tip position, which is a circular hole. The photoelectric sensor is provided on the moving path of the transport module from the pipette tip seat to the cell enrichment module.
[0026] Furthermore, the slide making module includes a workbench and a slide making clamp assembly. The workbench is composed of a plurality of workstations, and the shape of each workstation is a groove adapted to the slide making clamp assembly. The slide making clamp assembly includes a slide holder, a sedimentation chamber and a slide, a sealing rubber ring is provided between the sedimentation chamber and the slide, and the sedimentation chamber is connected to the slide holder through a clip.
[0027] Furthermore, it also includes a solid waste collection module, which includes a tube removal assembly and a waste collection box. The tube removal assembly is arranged directly above the waste collection box, and includes a support plate and a gun removal plate installed on the support plate. The gun removal plate is a horizontally arranged plate-like structure, and has an escape portion. The escape portion is a U-shaped opening, and the size of the opening of the escape portion is larger than the diameter of the sleeve and smaller than the diameter of the top of the disposable pipette tip, and the size of the escape portion gradually decreases from the opening to the inside. The number of tube removal assemblies is the same as that of the suction and injection assembly.
[0028] On the other hand, a method for preparing a cell slide is also provided, using the above-mentioned fully automatic liquid-based cell slide making machine, characterized in that it includes the following steps:
[0029] S1, sample enrichment: First, the diagnostic components such as cells are deposited at the bottom tip of the sample bottle through the centrifugal action of the cell enrichment module; then the supernatant after centrifugation is poured out by the waste liquid dumping device; finally, the reagent is injected into the cell sediment through the suction and injection mechanism of the transport module, and the sample is mixed by suction;
[0030] S2, sample transfer: a certain amount of mixed sample is sucked into the disposable pipette tip through the negative pressure generated by the suction and injection mechanism of the transport module, and the sample is transported to the sedimentation chamber of the film making module;
[0031] S3, sedimentation preparation: let the sample in the sedimentation chamber stand for 5-20 minutes, and the cells and other diagnostic components in the sample will naturally settle onto the glass slide under the action of gravity;
[0032] S4, staining and transparency: The liquid suction and injection mechanism of the transport module is used to repeatedly inject and absorb different reagents such as dye solution, alcohol, water, buffer solution and transparent solution into the sedimentation bin of the preparation module to complete the staining and transparency of the cells.
[0033] Beneficial effects of the present invention:
[0034] By coordinating the transport module with the liquid suction and injection mechanism with the cell enrichment module, a slice making machine with a high degree of automation, a compact and simple structure and a high success rate is obtained.
[0035] Among them, the transfer module interacts with the self-balancing component through the control module, and can automatically balance as needed, reducing labor. After the waste liquid dumping device discharges the supernatant of the centrifuged sample by dumping, the transfer module realizes sample transfer through the disposable pipette tip installed on it, and can also realize multiple injections and aspirations of different reagents through the aspiration needle and injection needle on it. Centrifugal balancing, sample transfer, and aspiration and injection functions can be completed by only one robotic arm, simplifying the mechanical structure. In addition, the transfer module combines with a photoelectric sensor to detect whether the disposable pipette tip is successfully grabbed, thereby improving the success rate of film production. BRIEF DESCRIPTION OF THE DRAWINGS
[0036] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings required for use in the description of the embodiments of the present invention will be briefly introduced below. Obviously, the accompanying drawings in the following description are only some embodiments of the present invention. For ordinary technicians in this field, other accompanying drawings can be obtained based on these accompanying drawings without paying creative labor.
[0037] Figure 1 This is a schematic diagram of the fully automatic liquid-based cell slide making machine of the present invention;
[0038] Figure 2 This is a schematic diagram of the fully automatic liquid-based cell slide making machine of the present invention;
[0039] Figure 3 This is a schematic diagram of the fully automatic liquid-based cell slide making machine of the present invention;
[0040] Figure 4 This is a schematic diagram of the fully automatic liquid-based cell slide making machine of the present invention;
[0041] Figure 5 It is a schematic diagram of the transport module of the fully automatic liquid-based cell slide making machine of the present invention;
[0042] Figure 6 It is a schematic diagram of the liquid suction and injection mechanism of the fully automatic liquid-based cell slice making machine of the present invention;
[0043] Figure 7 It is a schematic diagram of the liquid aspiration and injection component of the fully automatic liquid-based cell slice making machine of the present invention;
[0044] Figure 8 It is a schematic diagram of a waste liquid collecting device and a waste liquid dumping device of the fully automatic liquid-based cell slice making machine of the present invention;
[0045] Fig. 9 It is a schematic diagram of a waste liquid collecting device and a waste liquid dumping device of the fully automatic liquid-based cell slice making machine of the present invention;
[0046] Fig.10 It is a schematic diagram of a waste liquid collecting device and a waste liquid dumping device of the fully automatic liquid-based cell slice making machine of the present invention;
[0047] Fig.11 It is a schematic diagram of a balancing block of the fully automatic liquid-based cell slide making machine of the present invention;
[0048] Fig.12 It is a schematic diagram of the slide making clamp assembly of the fully automatic liquid-based cell slide making machine of the present invention.
[0049] in:
[0050] 1. Fully automatic liquid-based cell slice making machine; 2. Transport module; 3. Cell enrichment module; 4. Pipette tip module; 5. Slice making module; 6. Robotic arm; 7. Suction and injection mechanism; 8. Suction and injection assembly; 9. Cannula; 10. Suction needle; 11. Injection needle; 12. Centrifugal turntable; 13. First drive device; 14. Waste liquid dumping device; 15. Self-balancing assembly; 16. Sample bottle bearing seat; 17. Shaft; 18. Sample bottle; 19. Sample bottle push rod; 20. , detection unit; 21, balancing block; 22, transfer suction cup; 23, X arm; 24, Y arm; 25, Z arm; 26, first end of aspiration needle; 27, first waste liquid pipeline; 28, waste liquid bottle; 29, first pump; 30, first valve; 32, upper end of injection needle; 33, reagent pipeline; 34, reagent bottle; 35, second pump; 36, second valve; 37, second end of aspiration needle; 38, horizontal push rod; 39, vertical push rod; 40, first vertical arm; 41, first Horizontal arm; 42, second driving device; 43, second vertical arm; 44, second horizontal arm; 45, third driving device; 46, fixed block; 47, waste liquid collecting device; 48, waste liquid receiving tray; 49, second waste liquid pipeline; 50, tray bottom; 51, inner tray wall; 52, outer tray wall; 53, recessed space; 54, waste liquid outlet; 55, third valve; 56, anti-slip pad; 57, positioning sensor; 58, bottle detection sensor; 59, component one; 60, component two ; 61. Pipette tip seat; 62. Photoelectric sensor; 63. Pipette tip position; 64. Workbench; 65. Slide clamp assembly; 66. Work station; 67. Slide holder; 68. Sedimentation bin; 69. Slide; 70. Sealing rubber ring; 71. Clip; 72. Solid waste collection module; 73. Remove tube assembly; 74. Waste collection box; 75. Support plate; 76. Remove gun plate; 77. Avoidance part; 78. Disposable pipette tip; 79. Socket; 80. Rinse tube. DETAILED DESCRIPTION
[0051] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are 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 creative work are within the scope of protection of the present invention.
[0052] like Figure 1-4 As shown, the present invention provides a fully automatic liquid-based cell slide making machine 1, comprising: a transport module 2, a cell enrichment module 3, a pipette tip module 4 and a slide making module 5, wherein the cell enrichment module 3, the pipette tip module 4 and the slide making module 5 are arranged in sequence, and the transport module 2 is arranged above the cell enrichment module 3, the pipette tip module 4 and the slide making module 5. The transport module 2 comprises a mechanical arm 6 and a liquid suction and injection mechanism 7, and the liquid suction and injection mechanism 7 is fixedly mounted on the mechanical arm 6. The cell enrichment module 3 comprises: a centrifugal turntable 12, a waste liquid dumping device 14, a self-leveling component 15 and a first driving device 13. The outer periphery of the centrifugal turntable 12 is evenly provided with sample bottle holders 16 for carrying sample bottles 18. Both sides of the upper part of the sample bottle holder 16 are connected to the axis of the centrifugal turntable 12, and the sample bottle holder 16 can swing around the axis 17. The waste liquid dumping device 14 is composed of a sample bottle push rod 19 , and the sample bottle push rod 19 can push the sample bottle supporting seat 16 to make the sample bottle supporting seat 16 swing along the axis 17 .
[0053] The mechanical arm 6 on the transport module 2 is used to drive the suction and injection mechanism 7 to move inside the fully automatic liquid-based cell slide making machine 1, and complete the various steps of slide making between different modules, including mixing samples, transferring samples, adding reagents, and sucking and discharging waste liquid. The centrifugal turntable 12 on the cell enrichment module 3 is used to enrich cells in the sample, and the waste liquid dumping device 14 is used to discharge the supernatant after centrifugation, so that the centrifugal precipitate of cells with diagnostic significance remains at the bottom of the sample bottle. The slide making module 5 is used for sedimentation slide making and staining of cell samples, and the pipette tip module 4 is used to load disposable pipette tips 78.
[0054] Specifically, first, the cell enrichment module 3 deposits the cell sample stored in the sample bottle 18 at the bottom tip of the sample bottle 18 through centrifugation, that is, the centrifugal turntable 12 rotates, and the sample bottle support seat 16 swings around the rotating shaft 17 to a horizontal state under the action of centrifugal force, the centrifugal radius increases, and the centrifugal effect is good. After centrifugation, the precipitate gathers at the pointed bottom of the sample bottle 18, which is convenient for subsequent mixing.
[0055] Then, the waste liquid dumping device 14 pushes the sample bottle 18, and the sample bottle 18 swings around the axis 17 in the sample bottle support seat 16, so that the sample bottle 18 swings to a horizontal state, or even makes the mouth of the sample bottle 18 lower than the bottom of the bottle, and the supernatant after centrifugation in the sample bottle 18 automatically flows out under the action of gravity, and then the waste liquid dumping device 14 is reset, and the sample bottle 18 automatically returns to a vertical state. This operation only leaves cells with diagnostic significance in the sample bottle 18, achieving the purpose of enriching cells.
[0056] Then, the liquid suction and injection mechanism 7 on the transport module 2 picks up the disposable pipette tip 78 in the pipette tip module 4 by plugging, and injects liquid into the enriched cells, resuspends the cells in the liquid, and mixes them. The resuspended cells are then transferred from the enrichment module 3 to the film making module 5 using the disposable pipette tip 78.
[0057] Finally, the liquid injection mechanism 7 on the transport module 2 injects reagents and drains waste liquid into the slide making module 5, assisting the slide making module 5 in completing slide making and staining. It can be understood that slide making usually refers to sedimentation slide making, and staining usually refers to cell staining.
[0058] Through the above-mentioned implementation, the cooperation between the centrifugal turntable 12 and the waste liquid dumping device 14 of the cell enrichment module 3 can automatically complete the operations of centrifugation and dumping of supernatant without human intervention to obtain enriched cells.
[0059] Through the above implementation, the transport module 2 cooperates with the disposable pipette tip 78 to complete the resuspension, mixing and transfer of the enriched cells, and the different reagents are injected and the waste liquid of each step of the preparation process is sucked and discharged through the aspiration and injection component 8 of the transport module 2 to complete the preparation and staining.
[0060] The advantages of the above embodiment are: the mechanical arm for sucking centrifugal supernatant is abandoned, and a waste liquid dumping device 14 with a simple structure is adopted to naturally dump the supernatant, and only one mechanical arm 6 is retained for resuspending, mixing and transferring cells, so that the fully automatic liquid-based cell slice making machine of the present invention is compact and simple in structure and easy to maintain. In addition, the independent waste liquid dumping device 14 can free the transport module 2 from the work of waste liquid discharge, so that waste liquid dumping and sample transfer can be carried out simultaneously, thereby improving work efficiency.
[0061] Further, such as Figure 8-11 As shown, the self-balancing component 15 includes a detection unit 20, a plurality of balancing blocks 21 and a transport suction cup 22; the detection unit 20 detects whether the sample bottles in the centrifugal turntable 12 are balanced, and records the sample bottle holders 16 that need to be balanced, and the transport suction cup 22 is fixed on the transport module 2, and the robot arm 6 drives the transport suction cup 22 to absorb the balancing block 21 and place it in the sample bottle holder 16 that needs to be balanced.
[0062] The self-balancing component 15 is used for automatic balancing before centrifugation, which reduces labor and improves the degree of automation.
[0063] The specific process of automatic balancing is as follows: the sample bottle 18 storing the cell sample is placed in the sample bottle holder 16 of the cell enrichment module 3; the detection unit 20 of the self-balancing component 15 detects whether the sample bottle 18 is balanced, and records the sample bottle holder 16 that needs to be balanced, and transmits the information to the controller; the controller controls the robotic arm 6 to drive the transfer suction cup 22 to absorb the balancing block 21, and places it in the sample bottle holder 16 that needs to be balanced, thereby realizing the automatic balancing function.
[0064] Through the above implementation, the cooperation between the self-balancing component and the transport module 2 automatically completes the balancing work of the cell enrichment module before centrifugal enrichment of cells, without manual intervention, and with a high degree of automation.
[0065] In summary, through the above implementation, the cell enrichment module 3, the transport module 2 and the slide making module 5 work together to complete the entire process of preparing glass slide specimens from samples collected from the laboratory with almost no human intervention. The degree of automation is high, and the fully automatic liquid-based cell slide making machine has a compact and simple structure and is easy to maintain.
[0066] Further, such as Figure 5-7 As shown, the robot arm 6 includes: an X arm 23, a Y arm 24 and a Z arm 25. The X arm 23 is movably mounted on one side of the film-making module, the Y arm 24 is movably mounted on the X arm 23, the Z arm 25 is movably mounted on the Y arm 24, and the liquid suction and injection mechanism 7 is fixedly arranged on the Z arm 25.
[0067] Specifically, the fully automatic liquid-based cell preparation machine is provided with a vertical plate on one side of the preparation module, and the vertical plate can be located on the side of the preparation module, and at this time, the vertical plate is parallel to the connection line of the cell enrichment module 3, the pipette tip module 4 and the preparation module 5; the vertical plate can also be arranged in sequence with the cell enrichment module 3, the pipette tip module 4 and the preparation module 5, and at this time, the vertical plate is perpendicular to the connection line of the cell enrichment module 3, the pipette tip module 4 and the preparation module 5.
[0068] The vertical plate is fixedly mounted with a first motor, a first guide rail and a first belt. The first motor is fixedly arranged at one end of the vertical plate. The first belt is arranged horizontally, with one end passing around a first driving wheel on the output shaft of the first motor and the other end passing around a first driven wheel fixed on the vertical plate; the first motor can drive the first belt to reciprocate horizontally. The first guide rail is fixedly arranged on the vertical plate, and the first guide rail is arranged parallel to and adjacent to the first belt.
[0069] The X-arm 23 is mounted on the first belt and the first guide rail.
[0070] The X-arm 23 includes an X-slider (not shown in the figure) and an X-support member (not shown in the figure).
[0071] One end of the X slider is fixedly arranged on the first belt, and the other end is movably arranged on the first guide rail. The X slider can move back and forth horizontally (in the X direction) along the first guide rail under the drive of the first belt. The X support member is fixedly connected to the X slider.
[0072] The first motor drives the first belt to move reciprocatingly horizontally, the moving first belt drives the X slider to move reciprocatingly horizontally along the first guide rail, and the moving X slider drives the X support to move reciprocatingly horizontally, so as to realize the movement of the X arm in the X direction.
[0073] The X-support is also fixedly mounted with a second motor, a second guide rail, and a second belt. The second motor is fixedly mounted at one end of the X-support, and the second belt is horizontally arranged and perpendicular to the first belt. One end of the second belt passes around the second driving wheel on the output shaft of the second motor, and the other end passes around the second driven wheel fixed on the X-support. The second motor can drive the second belt to reciprocate horizontally. The second guide rail is fixedly mounted on the X-support, and the second guide rail is arranged parallel to and adjacent to the second belt.
[0074] The Y arm 24 is mounted on the second belt and the second guide rail.
[0075] The Y arm 24 includes a Y slider (not shown in the figure) and a Y support member (not shown in the figure).
[0076] One end of the Y slider is fixedly arranged on the second belt, and the other end is movably arranged on the second guide rail. The Y slider can move back and forth horizontally (in the Y direction) along the second guide rail driven by the second belt. The Y support member is fixedly connected to the Y slider.
[0077] The second motor drives the second belt to move reciprocatingly horizontally, the moving second belt drives the Y slider to move reciprocatingly horizontally along the second guide rail, and the moving Y slider drives the Y support to move reciprocatingly horizontally, thereby realizing the movement of the Y arm in the Y direction.
[0078] Since the Y arm 24 is movably mounted on the X arm 23 , the Y arm can move in the X direction driven by the X arm, that is, the Y arm can move in both the X and Y directions.
[0079] The Y support is also fixedly mounted with a third motor, a third guide rail and a third belt. The third motor is fixedly mounted at one end of the Y support. The third belt is arranged horizontally and longitudinally, and is perpendicular to the second belt. One end of the third belt passes around the third driving wheel on the output shaft of the third motor, and the other end passes around the third driven wheel fixed on the Y support. The third motor can drive the third belt to reciprocate horizontally. The third guide rail is fixedly mounted on the Y support, and the third guide rail is arranged parallel to and adjacent to the third belt.
[0080] The Z arm 25 is mounted on the third belt and the third guide rail.
[0081] The Z arm 25 includes a Z slider (not shown in the figure) and a Z support member (not shown in the figure).
[0082] One end of the Z slider is fixedly arranged on the third belt, and the other end is movably arranged on the third guide rail. The Z slider can move back and forth longitudinally (in the Z direction) along the third guide rail under the drive of the third belt. The Z support member is fixedly connected to the Z slider.
[0083] The third motor drives the third belt to move reciprocatingly horizontally, the moving third belt drives the Z slider to move reciprocatingly horizontally along the third guide rail, and the moving Z slider drives the Z support to move reciprocatingly horizontally, thereby realizing the movement of the Z arm in the Z direction.
[0084] Since the Z arm 25 is movably mounted on the Y arm 24 , the Z arm can move in the X and Y directions driven by the Y arm, that is, the Z arm can move in the X, Y and Z directions.
[0085] The liquid suction and injection mechanism 7 is fixedly mounted on the Z support member and can move in the X, Y and Z directions driven by the Z arm.
[0086] That is to say, through the arrangement of the X-arm 23, the Y-arm 24 and the Z-arm 25, the suction and injection mechanism 7 can move freely in the working space, so as to grab the disposable pipette tip 78 at any position, transfer the samples in the sample bottles at different positions to the slide making clamps at the corresponding positions, and perform suction and injection operations on the slide making clamps at any position.
[0087] That is, the fully automatic liquid-based cell slide making machine of the present invention can complete sample transfer and liquid aspiration and injection operations by only one mechanical arm 6, thereby simplifying the mechanical structure.
[0088] Further, such as Figure 5-7 As shown, the aspiration and injection mechanism 7 includes a plurality of aspiration and injection components 8, and the aspiration and injection components 8 include a sleeve 9 and a suction needle 10 and an injection needle 11 inside the sleeve 9, and the suction needle 10 penetrates the sleeve 9 and extends out.
[0089] First, the aspiration needle 10 is used to extract the waste liquid generated in each step of the film-making process from the film-making module 5, and the injection needle 11 is used to inject different reagents required for each step of the film-making process into the film-making module 5 to assist in film-making.
[0090] Specifically, the aspiration needle 10 and the injection needle 11 are both capillary steel tubes with a diameter of 1-5 mm, which are easily bent and deformed, affecting the aspiration and injection. The aspiration needle 10 and the injection needle 11 are integrated inside the sleeve 9, and the sleeve 9 has a larger diameter, which can better resist external pressure and protect the aspiration needle 10 and the injection needle 11.
[0091] The injection needle 11 is used for injection. In order to avoid cross contamination between different samples, the injection needle needs to be kept clean, so the injection needle 11 is placed in the sleeve 9 as a whole. Such a setting does not affect the injection function, and the sleeve 9 can protect the injection needle 11 from deformation to the greatest extent, and can also prevent the injection needle 11 from being contaminated by contacting the sample when the suction injection mechanism 7 is extended into various sample containers.
[0092] In order to ensure that the aspiration needle 10 successfully absorbs the waste liquid while avoiding cross contamination of the injection needle 11, in addition to taking the above-mentioned measure of placing the injection needle as a whole in the cannula 9, the present embodiment sets the aspiration needle 10 to penetrate the cannula 9 and extend out. In this way, the aspiration needle 10 can smoothly absorb the waste liquid, and when absorbing the waste liquid, only the aspiration needle 10 extending out of the cannula 9 contacts the waste liquid, while the cannula 9 and the injection needle 11 inside the cannula 9 do not contact the waste liquid, thereby avoiding cross contamination.
[0093] Moreover, the injection needle 11 can be used to clean the aspiration needle 10 when injecting liquid. Specifically, the aspiration needle 10 and the injection needle 11 are both arranged in the sleeve, and the aspiration needle 10 and the injection needle 11 are tightly fitted together, and the liquid outlet of the injection needle 11 contacts the outer wall of the aspiration needle. When the injection needle 11 injects liquid, the reagent flows out from the liquid outlet of the injection needle 11, flows down along the outer wall of the aspiration needle 10, and the clean reagent flushes the aspiration needle 10, which has the effect of cleaning the aspiration needle 10.
[0094] Secondly, the aspiration and injection mechanism 7 picks up the disposable pipette tip 78 by inserting the sleeve 9 , and resuspends and mixes the cell sample by the disposable pipette tip 78 , and then transfers the cell sample to the slide making module 5 .
[0095] Specifically, the sleeve 9 is driven by the mechanical arm 6 to move to the pipette tip module 4, move down, insert the sleeve 9 into the disposable pipette tip 78, pick up the disposable pipette tip 78, return to the cell enrichment module 3, and inject liquid into the centrifuged cells. The suction and injection mechanism 7 generates continuous negative pressure and positive pressure to suck and discharge the cell sample into and out of the disposable pipette tip 78, thereby resuspending and mixing the cell sample, and finally sucking the cell sample into the disposable pipette tip 78, and moving to the film making module 5 under the drive of the mechanical arm 6, injecting the cell sample into the film making module 5, and completing the transfer of the cell sample from the cell enrichment module 3 to the film making module 5.
[0096] Further, such as Figure 6As shown, the first end 26 of the aspiration needle is connected to the waste liquid bottle 28 through the first waste liquid pipeline 27, the first waste liquid pipeline 27 is provided with a first pump 29 and a first valve 30, and the second end 37 of the aspiration needle is bent. The upper end 32 of the injection needle is connected to the reagent bottle 34 through the reagent pipeline 33, and the reagent pipeline 33 is provided with a second pump 35 and a second valve 36. A controller is also included, the controller is electrically connected to the first pump 29 and the first valve 30 and the second pump 35 and the second valve 36, and the controller controls the switch of the first pump 29 and the first valve 30 and the second pump 35 and the second valve 36.
[0097] Specifically, the controller controls the opening and closing of the second pump 35 and the second valve 36 on the reagent pipeline 33, so that the corresponding reagent is injected into the sample bottle 18 of the cell enrichment module 3 or the area of the preparation module 5 through the injection needle 11 to complete the corresponding preparation steps.
[0098] The controller controls the opening and closing of the first pump 29 and the first valve 30 on the first waste liquid pipeline 27, so that the liquid aspiration needle 10 absorbs the waste liquid in the film-making module 5, so as to carry out the subsequent film-making steps.
[0099] As a possible implementation, Figure 7 As shown, there are 1 to 5 injection needles 11, which are used to inject different reagents respectively.
[0100] Specifically, cell preparation and staining often require 1-5 reagents with different physical and chemical properties, which need to be transported through different pipelines to prevent reagent mixing, affect the physical and chemical properties of the reagents, cause preparation failure, and affect the staining effect.
[0101] In this embodiment, 1 to 5 injection needles 11 and the aspiration needle 10 are integrated into one sleeve, which meets the requirements of injecting a variety of different reagents while maintaining a compact structure.
[0102] As a possible implementation, Figure 7 As shown, the second end 37 of the pipette needle is bent.
[0103] Specifically, when the aspiration needle 10 aspirates, the curved lower end can be as close to the cell layer on the glass slide 69 as possible, so as to aspirate as much waste liquid above the cell layer as possible, while preventing the sharp lower end 37 from directly contacting the cell layer and damaging the cell layer.
[0104] At the same time, when the injection needle 11 injects liquid, the liquid flows out of the injection needle 11 and flows down along the aspiration needle 10. Under the guidance of the aspiration needle 10, the liquid flows down along the curved top of the aspiration needle 10, and will not directly impact the cell layer vertically, thereby preventing damage to the cell layer.
[0105] Further, such as Figure 5 As shown, the suction and injection components 8 are 1-5 groups, which are arranged in a line and installed on the robot arm 6.
[0106] Specifically, the liquid suction and injection assembly 8 is used to add reagents to the sample and to suck and discharge waste liquid. One group of liquid suction and injection assemblies 8 can process one sample, and 1-5 groups of liquid suction and injection assemblies 8 can process 1-5 samples at the same time, thereby improving the sample processing efficiency.
[0107] As a possible implementation, Figure 1-4 As shown, the aspiration and injection mechanism 7 generates continuous positive pressure and negative pressure, so that the disposable pipette tip 78 repeatedly aspirates and discharges the sample in the sample bottle 18, thereby achieving the purpose of resuspending and mixing the sample.
[0108] It is understandable that there are various specifications of commercially available disposable pipette tips. The suction and injection mechanism 7 of this embodiment can set a suitable negative pressure value according to the specifications of the disposable pipette tip, so that the volume of the sample sucked by the disposable pipette tip is adapted to its specifications, that is, the sucked sample will only be in the disposable pipette tip, and the sample will not be sucked into the inner cavity of the sleeve 9. Each disposable pipette tip only processes the sample in a single sample bottle and is discarded after use. The sample only contacts the disposable pipette tip and does not contact the suction and injection mechanism to avoid contamination.
[0109] Further, such as Figure 8-10 As shown, the sample bottle push rod 19 includes a horizontal push rod 38 and a vertical push rod 39 , and the horizontal push rod 38 is located above the vertical push rod 39 .
[0110] The horizontal push rod 38 is located at the upper part of the sample bottle supporting seat 16, and includes a first vertical arm 40, a first horizontal arm 41 and a second driving device 42. The first vertical arm 40 and the first horizontal arm 41 are connected in a T shape. The first horizontal arm 41 is perpendicular to the radius of the centrifugal turntable 12. The second driving device 42 is connected to the first vertical arm 40, which can drive the horizontal push rod 38 to move toward the center of the centrifugal turntable 12, so that the first horizontal arm 41 contacts the upper part of the sample bottle in the sample bottle supporting seat 16.
[0111] The vertical push rod 39 is located below the sample bottle support 16, and includes a second vertical arm 43, a second horizontal arm 44 and a third driving device 45. The second vertical arm 43 and the second horizontal arm 44 are connected in a T shape. The second horizontal arm 44 is perpendicular to the radius of the centrifugal turntable 12. The third driving device 45 is connected to the second vertical arm 43, which can drive the vertical push rod 39 to move in a vertical upward direction, so that the second horizontal arm 44 contacts the sample bottle support 16.
[0112] After the horizontal push rod is pushed, it contacts the upper part of the side wall of the sample bottle, and can push the sample bottle in the horizontal direction, so that the sample bottle drives the sample bottle supporting seat to swing and tilt around the axis; after the vertical push rod is pushed, it contacts the lower part of the side wall of the inclined sample bottle supporting seat, and can push the sample bottle supporting seat in the vertical direction, so that the sample bottle supporting seat drives the sample bottle to continue to swing and tilt around the axis.
[0113] Traditional liquid-based cell slide making machines use suction to discharge waste liquid (supernatant after centrifugation), that is, the mechanical arm drives the gas-liquid pipeline to enter each sample bottle, and by generating negative pressure, the waste liquid in the sample bottle is sucked and transferred into the waste liquid bottle. This method must have the coordination of pumps, valves, pipelines and mechanical arms, and the mechanical structure is complex, with many accessories and a high failure rate.
[0114] Therefore, the present application abandons this suction-type method of discharging waste liquid, and adopts a simple-structured dumping device to push the sample bottle down, so that the waste liquid automatically flows out under the action of gravity.
[0115] Specifically, when the waste liquid (supernatant) needs to be dumped after centrifugation, the second driving device 42 drives the first vertical arm 40 of the horizontal push rod 38 to move, and drives the first horizontal arm 41 to move toward the center of the centrifugal turntable 12, contacting the upper part of the sample bottle support seat 16, and continues to move, pushing the sample bottle support seat 16 to swing around the rotation axis 17, so that the sample bottle support seat 16 and the sample bottle 18 placed therein swing and tilt around the rotation axis 17, at which time the lower side of the sample bottle support seat 16 is lifted to the top of the vertical push rod. Then the third driving device 45 drives the second vertical arm 43 of the vertical push rod 39 to move upward, and drives the second horizontal arm 44 to move upward, contacting the lower side of the inclined sample bottle support seat 16, and continues to move, pushing the sample bottle support seat 16 to continue to swing along the rotation axis 17, driving the sample bottle 18 to continue to swing around the rotation axis 17, until the mouth of the sample bottle is lower than the bottom of the bottle, and the waste liquid flows out of the sample bottle 18 by itself under the action of gravity. The horizontal push rod 38 and the vertical push rod 39 cooperate with each other to discharge the waste liquid in the sample bottle.
[0116] After the waste liquid is discharged, the vertical push rod 39 retreats and resets, the horizontal push rod 38 retreats and resets, and the sample bottle 18 and the sample bottle supporting seat 16 automatically return to the vertical state under the action of gravity.
[0117] It is understandable that the horizontal push rod 38 and the vertical push rod 39 constituting the sample bottle push rod 19 are both one piece and can be disposed at any position on the periphery of the centrifugal turntable 12 .
[0118] Specifically, the sample bottles are moved to the position of the sample bottle push rod 19 in sequence with the rotation of the centrifugal turntable 12, and are pushed down by the sample bottle push rod 19 to pour out the waste liquid. The sample bottle push rod 19 is arranged at any position of the periphery of the centrifugal turntable 12, and can push down any sample bottle through the rotation of the centrifugal turntable 12 to complete the waste liquid pouring work.
[0119] As a possible implementation, the height of the sample bottle 18 is greater than the inner cavity height of the sample bottle support seat 16. When the sample bottle 18 is placed in the sample bottle support seat 16, the upper part of the sample bottle is higher than the sample bottle support seat 16. The horizontal push rod 38 of the sample bottle push rod 19 can push the upper part of the sample bottle 18 in the sample bottle support seat 16, so that the sample bottle 18 drives the sample bottle support seat 16 to swing along the axis 17.
[0120] The benefit of such an arrangement is that when dumping waste liquid, the horizontal push rod 38 can directly push the sample bottle without pushing the sample bottle support 16. Therefore, the sample bottle support 16 can be connected to the axis of the centrifugal turntable 12 at the uppermost part. In this way, the center of gravity of the sample bottle support 16 is at a position far below the axis. After the external force is removed, it is beneficial for the sample bottle support 16 to quickly return to a vertical state under the action of gravity.
[0121] Further, such as Figure 8-10 As shown, a fixing block 46 is disposed in the middle of the second cross arm 44 . The size of the fixing block 46 matches the distance between the two sample bottle supporting seats 16 , and is used to fix the sample bottle supporting seats 16 .
[0122] It is understandable that the sample bottle push rod 19 can push one sample bottle at a time to complete the waste liquid dumping, and can also push two sample bottles at a time to complete the waste liquid dumping.
[0123] Pushing one sample bottle at a time is inefficient. Pushing two sample bottles at a time can double the efficiency. Both methods have a problem, that is, the centrifugal turntable 12 itself is rotatable, and when the sample bottle push rod 19 pushes the sample bottle, the uneven force will cause the centrifugal turntable to rotate, causing the sample bottle to slip off the sample bottle push rod 19, affecting the dumping of waste liquid.
[0124] In this embodiment, a fixing block 46 is provided in the middle of the second horizontal arm 44. The size of the fixing block 46 is adapted to the distance between the two sample bottle holders 16. When the second horizontal arm 44 of the vertical push rod 39 contacts the sample bottle 18, the fixing block 46 is inserted between the two sample bottles 18 to fix the sample bottles 18, thereby preventing the centrifugal turntable 12 from continuing to rotate under the action of inertia, stabilizing the sample bottles 18, making it more convenient and easy to pour the centrifugal supernatant (i.e., waste liquid), and facilitating the waste liquid treatment.
[0125] Further, such as Figure 8-10 As shown, it also includes a waste liquid collecting device 47. The waste liquid collecting device 47 includes a waste liquid receiving tray 48, a second waste liquid pipeline 49 and a waste liquid bottle 28.
[0126] The waste liquid receiving tray 48 is arranged below the centrifugal turntable 12 and is in a circular ring shape; the waste liquid receiving tray 48 includes a tray bottom 50, an inner tray wall 51 and an outer tray wall 52, the inner tray wall 51 is located in a circle around the inner periphery of the tray bottom 50, and the outer tray wall 52 is located in a circle around the outer periphery of the tray bottom 50, the inner tray wall 51 and the outer tray wall 52 protrude from the tray bottom 50, and the tray bottom 50, the inner tray wall 51 and the outer tray wall 52 together form an annular recessed space 53, and the recessed space 53 can be used to receive waste liquid; a waste liquid port 54 is provided on the tray bottom 50, which passes through from top to bottom; the lower end of the waste liquid port 54 is connected to the waste liquid bottle 28 through the second waste liquid pipeline 49, and a third valve 55 is provided on the pipeline, and the switch of the third valve 55 is controlled by the controller.
[0127] The waste liquid collecting device 47 is used to collect the supernatant (waste liquid) generated after the cell enrichment module 3 is centrifuged.
[0128] Specifically, after the waste liquid is poured out by the waste liquid dumping device 14 , it flows into the waste liquid receiving tray 48 , the third valve 55 is opened, and the waste liquid flows into the waste liquid bottle 28 through the waste liquid port 54 and the second waste liquid pipeline 49 .
[0129] The third valve 55 is usually closed and is opened only when the waste liquid is dumped. On the one hand, it can reduce the volatilization of the waste liquid in the waste liquid bottle into the environment to pollute the environment. On the other hand, it can provide a closed environment for the pipeline system of the tablet making machine, facilitating the generation of negative pressure and positive pressure in the pipeline system.
[0130] As a possible implementation, the waste liquid port 54 is located below the sample bottle push rod 19. Such a configuration is conducive to the waste liquid flowing into the waste liquid bottle quickly, shortening the time that the waste liquid stays in the waste liquid receiving tray 48, and reducing environmental pollution.
[0131] As a possible implementation, Figure 8-10 As shown, an anti-skid pad 56 is provided on the outer disk wall 52 at a position corresponding to the sample bottle push rod assembly, and is used to limit the position of the sample bottle 18 after the sample bottle push rod assembly pushes the sample bottle 18 to a horizontal position.
[0132] It is understandable that the sample bottle 18 is naturally placed in the sample bottle support seat 16 without a limiting device. When the sample bottle 18 is tilted to the lowest position, it contacts the upper surface of the outer plate wall 52 of the waste liquid receiving tray 48. At this time, the bottle mouth is lower than the bottle bottom, and the sample bottle 18 is easy to slide out of the sample bottle support seat 16, resulting in the subsequent sample transfer failure because the sample bottle slides out. By providing an anti-skid pad with a large friction coefficient at the position where the sample bottle 18 contacts the upper surface of the outer plate wall 52 of the waste liquid receiving tray 48, the sample bottle 18 can be prevented from sliding out of the sample bottle support seat 16.
[0133] As a possible implementation, Figure 8-10As shown, a flushing pipe is also included. The flushing pipe is arranged above the waste liquid port 54 and is used to clean the waste liquid port 54 to prevent chemical reagent crystallization from blocking the waste liquid port 54 and to prevent chemical reagent residue from corroding the waste liquid receiving tray and the waste liquid port.
[0134] As a possible implementation, Figure 1-4 As shown, the cell enrichment module 3 has a sealing cover that is folded open and closed.
[0135] When placing the sample bottle, the sealing cover is opened without affecting the operation of the experimenter.
[0136] During centrifugation, the sealing cover is closed to seal the cell enrichment module 3, which can prevent the sample or sample bottle from being thrown out of the cell enrichment module 3 during centrifugation, and can also prevent the aerosol generated by centrifugation from evaporating into the environment, thereby protecting the health of the experimenters.
[0137] The foldable sealing cover takes up little space, and can reduce the size of the fully automatic liquid-based cell preparation machine 1 as a whole.
[0138] Further, such as Figure 1-4 As shown, the detection unit 20 includes a positioning sensor 57 and a bottle detection sensor 58. The positioning sensor 57 includes a component 1 59 and a component 2 60. The component 1 59 is fixedly arranged on the centrifugal turntable 12 and rotates with the centrifugal turntable. The component 1 59 and the component 2 60 are used in conjunction to position the sample bottle support seat 16.
[0139] The bottle detection sensor 58 is disposed at one side of the centrifugal turntable 12 , slightly higher than the sample bottle support seat 16 . The bottle detection sensor 58 determines whether there is a sample bottle in the sample bottle support seat 16 .
[0140] The positioning sensor 57 and the bottle detection sensor 58 cooperate to confirm the sample bottle support 16 where the balancing block needs to be placed.
[0141] Specifically, the installation positions of the bottle detection sensor 58 and the positioning sensor 57 can be preset so that the bottle detection sensor 58 and the positioning sensor 57 differ in circumferential direction by at least one station. The position of each sample bottle support 16 is a station.
[0142] An example is given in which 24 sample bottle carriers 16 are arranged on the centrifugal turntable 12 and the positioning sensor 57 and the bottle detection sensor 58 are spaced 11 stations apart.
[0143] Component 1 59 rotates with the centrifugal turntable 12. When passing through component 2 60, component 2 60 receives the signal of component 1 59 and transmits a signal to the controller, recording the sample bottle holder 16 corresponding to the radius of component 1 as sample bottle holder No. 1. At this time, the sample bottle holder 16 detected by the bottle detection sensor 58 is sample bottle holder No. 13. The bottle detection sensor 58 starts to detect whether there is a sample bottle 18 in the sample bottle holder No. 13, and transmits the detection information to the controller. As the centrifugal turntable 12 rotates, the bottle detection sensor 58 detects whether there is a sample bottle 18 in each sample bottle holder in turn, and transmits the detection information to the controller until the centrifugal turntable 12 rotates one circle and the status of the sample bottles 18 in all sample bottle holders 16 is detected. The controller compares the information of the sample bottles 18 in the symmetrical sample bottle holders 16 according to the received information, and makes a judgment on whether to balance accordingly, and records the information of the sample bottle holders 16 that need to be balanced.
[0144] Further, such as Fig.11 As shown, the balancing block 21 is a columnar structure of the same weight as the sample bottle 18 , with a non-through insertion hole 79 in the middle, and the diameter of the insertion hole 79 is slightly larger than the sleeve 9 of the aspiration and injection component 8 .
[0145] Specifically, the controller controls the transfer module 2 to move above the balancing block 21, and moves the suction and injection mechanism 7 downward, so that the sleeve 9 penetrates into the insertion hole 79 of the balancing block 21. After the suction cup on the sleeve 9 contacts the top of the balancing block 21, the suction and injection mechanism 7 sucks vacuum, firmly sucks the balancing block 21, and under the drive of the transfer module 2, transfers it to the sample bottle support seat 16 that needs to be balanced, and completes the balancing. After centrifugation is completed, the transfer module 2 transfers the balancing block 21 to the storage seat.
[0146] As a possible implementation, each balancing block 21 is of equal weight to three sample bottles 18 .
[0147] The purpose of such arrangement is that when placing the sample bottles 18 manually, they can be placed in sequence along the sample positions without paying special attention to balancing. After the self-balancing component 15 detects the information of the sample bottles 18, it automatically places the balancing block 21 in the sample bottle bearing seat 16 that needs balancing for balancing.
[0148] Take the processing of 12 samples as an example: 12 sample bottles 18 are placed in the sample bottle holders No. 1-12 in sequence. After the self-balancing component 15 detects the information of the sample bottle 18, it sends the status information of the sample bottle 18 to the controller. The controller controls the transfer module 2 to move to the top of the balancing block 21, and moves the suction and injection mechanism 7 downward to make the sleeve 9 penetrate into the socket 79 of the balancing block 21. After the suction cup on the sleeve 9 contacts the top of the balancing block 21, the suction and injection mechanism 7 draws vacuum to firmly suck the balancing block 21, and driven by the transfer module 2, the four balancing blocks 21 are transferred to 14, 17. The sample bottle holders 16 of No. 1, 20 and 23 are balanced, that is, the three sample bottles 18 in the sample bottle holders 1, 2 and 3 are balanced with the balance block 21 in the sample bottle holder 14, the three sample bottles 18 in the sample bottle holders 4, 5 and 6 are balanced with the balance block 21 in the sample bottle holder 17, the three sample bottles 18 in the sample bottle holders 7, 8 and 9 are balanced with the balance block 21 in the sample bottle holder 20, and the three sample bottles 18 in the sample bottle holders 10, 11 and 12 are balanced with the balance block 21 in the sample bottle holder 23. After centrifugation is completed, the transfer module 2 transfers the balance block 21 to the storage seat.
[0149] Further, such as Figure 1-4 As shown, the pipette tip module 4 includes a pipette tip seat 61 and a photoelectric sensor 62. The pipette tip seat 61 is used to carry a disposable pipette tip 78; a pipette tip position 63 is provided on the pipette tip seat 61, and the pipette tip position is a circular hole, and the disposable pipette tip 78 can be stably placed in the circular hole of the pipette tip position 63.
[0150] It is understandable that the disposable pipette tip 78 can be installed on the sleeve 9 of the transfer module 2 in a plug-in manner.
[0151] Specifically, the aspiration and injection mechanism 7 is driven by the mechanical arm 6 to move above the pipette tip seat 61, moves downward to insert the sleeve 9 of the aspiration and injection assembly 8 into the disposable pipette tip 78, and continues to move downward until the disposable pipette tip 78 is stably inserted on the sleeve 9.
[0152] The robotic arm 6 drives the aspiration and injection mechanism 7 to move to the cell enrichment module 3, so that the sleeve 9 penetrates into the sample bottle 18, and uses the disposable pipette tip 78 to draw a quantitative sample. The robotic arm 6 drives the aspiration and injection mechanism 7 to move to the film making module 5, and injects the sample in the disposable pipette tip 78 into the film making module 5 for film making.
[0153] It can be understood that the photoelectric sensor 62 is arranged on the moving path of the transport module 2 from the pipette tip seat 61 to the cell enrichment module 3, and is used to detect whether the disposable pipette tip 78 is installed in place.
[0154] Specifically, after the disposable pipette tip 78 is installed by the sleeve 9, the transport module 2 drives the disposable pipette tip 78 to pass through the photoelectric sensor 62, and the photoelectric sensor 62 detects whether the disposable pipette tip 78 is installed in place. If the disposable pipette tip 78 is installed in place, the transport module 2 drives the disposable pipette tip 78 to continue to move to the cell enrichment module 3. If the disposable pipette tip 78 is not installed in place, the transport module 2 returns to the pipette tip module 4, re-inserts and installs the pipette tip 78, until the installation is successful, and the transport module 2 drives the disposable pipette tip 78 to continue to move to the cell enrichment module 3.
[0155] It is understandable that the transfer of samples depends on disposable pipette tips. Whether the disposable pipette tips are installed successfully or not directly determines whether the subsequent sample transfer is successful, which in turn affects whether the slide preparation and staining are successful. This embodiment performs detection at the step of installing the disposable pipette tips to ensure that the disposable pipette tips are installed successfully, thereby ensuring the success of subsequent sample transfer, slide preparation and staining, and improving the success rate and production efficiency.
[0156] As a possible implementation, the pipette tip module 4 is disposed between the cell enrichment module 3 and the film making module 5 . Such an arrangement can reduce the movement distance of the transport module 2 .
[0157] As a possible implementation, the spacing between the pipette tip positions 63 is consistent with the spacing between the sleeves 9 of the aspiration and injection assembly 8. This arrangement allows all the sleeves 9 to be plugged into the disposable pipette tips 78 at the same time.
[0158] Further, such as Figure 1-4 As shown, the film-making module 5 includes a workbench 64 and a film-making clamp assembly 65 .
[0159] The workbench 64 is composed of a plurality of workstations 66 , each of which is shaped as a groove adapted to the film-making clamp assembly 65 .
[0160] The slide clamp assembly 65 includes a slide holder 67 , a sedimentation chamber 68 and a slide 69 . A sealing rubber ring 70 is provided between the sedimentation chamber 68 and the slide 69 . The sedimentation chamber 68 is connected to the slide holder 67 via a clip 71 .
[0161] The slide making clamp is assembled as follows: a slide 69 is placed on the slide holder 67, one end of the sedimentation chamber 68 with a sealing rubber ring 70 is placed on the slide 69, and the sedimentation chamber 68, the slide 69 and the slide holder 67 are fixed together by the clamps 71 adapted on the sedimentation chamber 68 and the slide holder 67. The sedimentation chamber 68 and the slide 69 form a sealed slide making space under the action of the sealing rubber ring 70, which is used to accommodate the sample for slide making.
[0162] The film-making clamp assembly 65 can be placed in the station 66 and move freely. The spacing between the centers of adjacent film-making stations 66 is consistent with the spacing between the sleeves 9 of the liquid suction and injection assembly 8.
[0163] The sedimentation preparation process is as follows: the transport module 2 transfers the sample from the cell enrichment module 3 to the sedimentation chamber 68, and the sample is left to stand in the preparation space composed of the sedimentation chamber 68, the glass slide 69 and the glass slide holder 67. The cells are deposited on the surface of the glass slide 69 under the action of gravity, forming a circular cell layer with the same diameter as the sedimentation chamber 68.
[0164] The film-making clamp assembly 65 is placed in the film-making station 66 . Due to the obstruction of the side wall of the film-making station 66 and the fact that it is not fixed by fastening measures, the film-making clamp assembly 65 can move freely in the space above the film-making station 66 .
[0165] Driven by the mechanical arm 6, the liquid suction and injection assembly 8 moves downward, so that the lower end of the sleeve 9 enters the sedimentation bin 68, and the lower end of the liquid suction needle 10 stops at the corresponding position of the sedimentation bin 68. It can be lowered to the middle position of the sedimentation bin 68 during injection, and can be lowered to a position close to the bottom of the sedimentation bin 68 during liquid suction. The mechanical arm 6 drives the liquid suction and injection assembly 8 to move horizontally to the right. When the lower end of the liquid suction needle 10 hits the inner wall of the sedimentation chamber 68, the sedimentation chamber 68 is driven to the right by the liquid suction needle 10, and the glass slide holder 67 is blocked by the right side wall of the slide preparation station 66. The mechanical arm 6 drives the liquid suction and injection assembly 8 to continue to move horizontally to the right. Under the continued driving force of the liquid suction needle 10, the glass slide holder 67 rotates and tilts around the right end of the glass slide holder 67 as an axis. Due to the obstruction of the front and rear side walls of the slide preparation station 66, the glass slide holder 67 will not rotate in other directions. When the external force is eliminated, the glass slide holder 67 can return to its original position under the action of gravity. When the liquid suction and injection assembly 8 moves horizontally to the left, front, and back, the process is the same as above.
[0166] The dyeing process is as follows: under the control of the controller, the liquid suction and injection component 8 injects different reagents into the preparation space in turn through different injection needles 11, and extracts the waste liquid generated during the preparation process from the preparation space through the liquid suction needle 10 and then introduces it into the waste liquid bottle 28.
[0167] During this process, the sedimentation bin 68 is tilted during injection and aspiration, and is horizontal at other times. It is understandable that during injection, the reagent flows down along the tilted side wall of the sedimentation bin 68 to cover the cell layer, which can prevent the reagent from directly impacting the cell layer and causing damage to the cell layer; during aspiration, the tilted sedimentation bin 68 can collect waste liquid and aspirate the waste liquid to the maximum extent.
[0168] Further, such as Figure 1-4As shown, it also includes a solid waste collection module 72, which includes a tube removal assembly 73 and a waste collection box 74. The tube removal assembly 73 is arranged directly above the waste collection box 74, and the solid waste collection module 72 is used to collect discarded disposable pipette tips 78.
[0169] The tube removal assembly 73 includes a support plate 75 and a gun removal plate 76. The gun removal plate 76 is installed on the upper part of the support plate 75. The gun removal plate 76 is a horizontally arranged plate-like structure and has an escape portion 77. The escape portion 77 is a U-shaped opening. The size of the opening of the escape portion 77 is larger than the diameter of the sleeve 9 and smaller than the diameter of the top of the disposable pipette tip 78. The size of the escape portion 77 gradually decreases from the opening to the inside, so that the sleeve 9 can easily enter the escape step, and after the sleeve 9 enters the escape portion 77, the disposable pipette tip 78 can be stuck under the escape step 77.
[0170] The number of the tube assembly 73 is not less than that of the suction and injection assembly 8, to ensure that each suction and injection assembly 8 has a corresponding tube assembly 73, and the disposable liquid transfer gun head 78 thereon is taken off. Preferably, the number of the tube assembly 73 is identical with that of the suction and injection assembly 8.
[0171] The spacing between adjacent tube-removing components 73 is consistent with the spacing between the sleeves 9 of the aspiration and injection component 8 to ensure that different sleeves 9 enter the corresponding tube-removing components 73 at the same time, and the disposable pipette tips 78 on all sleeves 9 are removed at the same time.
[0172] Specifically, the robotic arm 6 drives the liquid suction and injection mechanism 7 to the front end of the avoidance portion 77 of the tube removal assembly 73, and makes the sleeve 9 of the liquid suction and injection assembly 8 enter the interior of the gun removal plate 76 from the avoidance portion 77. The robotic arm 6 drives the liquid suction and injection mechanism 7 to move upward, so that the upper end of the disposable pipette tip 78 contacts the gun removal plate 76, is blocked by the gun removal plate 76, and cannot continue to move upward with the liquid suction and injection mechanism 7, thereby falling off the sleeve 9 and falling into the waste collection box 74 directly below the tube removal assembly 73.
[0173] On the other hand, a method for preparing a cell slide is also provided, which is prepared using the above-mentioned fully automatic liquid-based cell slide making machine, comprising the following steps:
[0174] S1, sample enrichment: first, the diagnostic components such as cells are deposited at the bottom tip of the sample bottle 18 through the centrifugal action of the cell enrichment module 3; then the supernatant after centrifugation is poured out by the waste liquid dumping device 14; finally, the reagent is injected into the cell sediment through the suction and injection mechanism 7 of the transport module 2, and the sample is mixed by suction.
[0175] S2, sample transfer: the suction and injection mechanism 7 of the transport module 2 generates negative pressure to suck a certain amount of mixed sample into the disposable pipette tip 78, and transports the sample to the sedimentation chamber 68 of the preparation module 5.
[0176] S3, sedimentation preparation: let the sample in the sedimentation chamber 68 stand for 5-20 minutes, and the diagnostic components such as cells in the sample naturally settle on the glass slide 69 under the action of gravity.
[0177] S4, staining: the liquid injection mechanism 7 of the transport module 2 injects and absorbs and discharges different reagents such as dye solution, alcohol, water, buffer solution and transparent solution into the sedimentation chamber 68 of the preparation module 5 for multiple times to complete the staining and transparency of the cells.
[0178] It should be noted that, in this article, the terms "include", "comprises" or any other variations thereof are intended to cover non-exclusive inclusion, so that a process, method, article or device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or device. In the absence of further restrictions, an element defined by the sentence "comprises a ..." does not exclude the existence of other identical elements in the process, method, article or device including the element.
[0179] The embodiments of the present invention are described above in conjunction with the accompanying drawings, but the present invention is not limited to the above-mentioned specific implementation modes, which are merely illustrative rather than restrictive. Under the guidance of the present invention, ordinary technicians in this field can also make many forms without departing from the scope of protection of the present invention and the claims, all of which are within the protection of the present invention.
Claims
1. A fully automatic liquid-based cell slide making machine, comprising: A transport module, a cell enrichment module, a pipette tip module and a film making module, wherein the cell enrichment module, the pipette tip module and the film making module are arranged in sequence, and the transport module is arranged above the cell enrichment module, the pipette tip module and the film making module; characterized in that, The transfer module includes a mechanical arm and a liquid suction and injection mechanism, and the liquid suction and injection mechanism is fixedly installed on the mechanical arm; The cell enrichment module includes: a centrifugal turntable, a waste liquid dumping device, a self-balancing component and a first driving device; The outer periphery of the centrifugal turntable is evenly provided with sample bottle bearing seats, both sides of the upper part of the sample bottle bearing seats are connected to the centrifugal turntable shaft, and the sample bottle bearing seats can swing around the shaft; The waste liquid dumping device is composed of a sample bottle push rod, which includes a horizontal push rod and a vertical push rod, and the horizontal push rod is located above the vertical push rod; the sample bottle push rod can push the sample bottle bearing seat to make the sample bottle bearing seat swing along the axis; The self-balancing assembly includes a detection unit, a plurality of balancing blocks and a transfer suction cup; The detection unit includes a positioning sensor and a bottle detection sensor. The positioning sensor includes component one and component two. Component one is fixedly arranged on the centrifugal turntable and rotates with the centrifugal turntable. Component one and component two are used in conjunction to position the sample bottle support seat. The bottle detection sensor is arranged on one side of the centrifugal turntable, slightly higher than the sample bottle support seat. The bottle detection sensor determines whether there is a sample bottle in the sample bottle support seat. The positioning sensor and the bottle detection sensor work together to confirm the sample bottle holder where the balancing block needs to be placed. The detection unit detects whether the sample bottle in the centrifugal turntable is balanced and records the sample bottle holder that needs to be balanced. The transfer suction cup is fixed on the transfer module, and the transfer suction cup is driven by the robotic arm to absorb the balancing block and place it in the sample bottle holder that needs to be balanced.
2. The fully automatic liquid-based cell slide making machine according to claim 1, characterized in that: The robotic arms include: X-arm, Y-arm and Z-arm; The X arm is movably mounted on one side of the film-making module, the Y arm is movably mounted on the X arm, and the Z arm is movably mounted on the Y arm; The liquid suction and injection mechanism is fixedly arranged on the Z arm.
3. The fully automatic liquid-based cell slide making machine according to claim 1, characterized in that: The liquid suction and injection mechanism comprises a plurality of liquid suction and injection components, wherein the liquid suction and injection components comprise a sleeve tube and a liquid suction needle and a liquid injection needle inside the sleeve tube, and the liquid suction needle penetrates through the sleeve tube and extends out.
4. The fully automatic liquid-based cell slide making machine according to claim 1, characterized in that: The first end of the aspiration needle is connected to the waste liquid bottle through a first waste liquid pipeline, a first pump and a first valve are arranged on the first waste liquid pipeline, and the second end of the aspiration needle is bent; The upper end of the injection needle is connected to the reagent bottle through a reagent pipeline, and a second pump and a second valve are arranged on the reagent pipeline; The device also includes a controller, which is electrically connected to the first pump and the first valve and the second pump and the second valve, and controls the switching of the first pump and the first valve and the second pump and the second valve.
5. The fully automatic liquid-based cell slide making machine according to claim 2, characterized in that: The suction and injection components are 1 to 5 groups, which are arranged in a line and installed on the robot arm.
6. The fully automatic liquid-based cell slide making machine according to claim 1, characterized in that: The horizontal push rod is located at the upper part of the sample bottle bearing seat, and includes a first vertical arm, a first horizontal arm and a second driving device. The first vertical arm and the first horizontal arm are connected in a T shape. The first horizontal arm is perpendicular to the radius of the centrifugal turntable. The second driving device is connected to the first vertical arm. The vertical push rod is located below the sample bottle bearing seat, and includes a second vertical arm, a second horizontal arm and a third driving device, the second vertical arm and the second horizontal arm are connected in a T shape, the second horizontal arm is perpendicular to the radius of the centrifugal turntable, and the third driving device is connected to the second vertical arm; After the horizontal push rod is pushed, it contacts the upper part of the side wall of the sample bottle, and can push the sample bottle in the horizontal direction, so that the sample bottle drives the sample bottle supporting seat to swing and tilt around the axis; after the vertical push rod is pushed, it contacts the lower part of the side wall of the inclined sample bottle supporting seat, and can push the sample bottle supporting seat in the vertical direction, so that the sample bottle supporting seat drives the sample bottle to continue to swing and tilt around the axis.
7. The fully automatic liquid-based cell slide making machine according to claim 6, characterized in that: A fixing block is arranged in the middle of the second cross arm, and the size of the fixing block is adapted to the distance between the two sample bottle bearing seats.
8. The fully automatic liquid-based cell slide making machine according to claim 1, characterized in that: It also includes a waste liquid collection device, which includes a waste liquid receiving tray, a second waste liquid pipeline and a waste liquid bottle; The waste liquid receiving plate is arranged below the centrifugal turntable and is in a circular shape. The waste liquid receiving plate includes a plate bottom, an inner plate wall and an outer plate wall. The inner plate wall is located in an inner circle of the plate bottom, and the outer plate wall is located in an outer circle of the plate bottom. The inner plate wall and the outer plate wall protrude from the plate bottom. The plate bottom is provided with a waste liquid port which passes through from top to bottom. The lower end of the waste liquid port is connected to the waste liquid bottle through a second waste liquid pipeline. A third valve is provided on the pipeline, and the switch of the third valve is controlled by a controller.
9. The fully automatic liquid-based cell slide making machine according to claim 1, characterized in that: The balance block is a columnar structure with the same weight as the sample bottle, with a non-through insertion hole in the middle, and the diameter of the insertion hole is slightly larger than the sleeve of the suction and injection component.
10. The fully automatic liquid-based cell slide making machine according to claim 1, characterized in that: The pipette tip module includes a pipette tip seat and a photoelectric sensor; A pipette tip position is arranged on the pipette tip seat, and the pipette tip position is a circular hole; The photoelectric sensor is arranged on the moving path of the transport module from the pipette head seat to the cell enrichment module.
11. The fully automatic liquid-based cell slide making machine according to claim 1, characterized in that: The film-making module includes a workbench and a film-making clamp assembly; The workbench is composed of a plurality of workstations, each of which is shaped as a groove adapted to the film making clamp assembly; The slide making clamp assembly comprises a slide holder, a sedimentation chamber and a slide. A sealing rubber ring is arranged between the sedimentation chamber and the slide. The sedimentation chamber is connected with the slide holder through a clip.
12. The fully automatic liquid-based cell slide making machine according to claim 1, characterized in that: It also includes a solid waste collection module, which includes a tube removal assembly and a waste collection box. The tube removal assembly is arranged directly above the waste collection box, and includes a support plate and a gun removal plate. The gun removal plate is installed on the support plate. The gun removal plate is a horizontally arranged plate-like structure, and has an avoidance portion. The avoidance portion is a U-shaped opening. The size of the opening of the avoidance portion is larger than the diameter of the sleeve and smaller than the diameter of the top of the disposable pipette tip, and the size of the avoidance portion gradually decreases from the opening to the inside. The number of tube removal components shall not be less than the number of liquid suction and injection components.
13. A method for preparing a cell slide, using the fully automatic liquid-based cell slide making machine according to claim 1, characterized in that: The following steps are involved: S1, sample enrichment: First, the cell diagnostic components are deposited at the bottom tip of the sample bottle through the centrifugal action of the cell enrichment module; then the supernatant after centrifugation is poured out by the waste liquid dumping device; finally, the reagent is injected into the cell sediment through the suction and injection mechanism of the transport module, and the sample is mixed by suction; S2, sample transfer: a certain amount of mixed sample is sucked into the disposable pipette tip through the negative pressure generated by the suction and injection mechanism of the transport module, and the sample is transported to the sedimentation chamber of the film making module; S3, sedimentation preparation: let the sample in the sedimentation chamber stand for 5-20 minutes, and the cell diagnostic components in the sample will naturally settle onto the glass slide under the action of gravity; S4, staining: The suction and injection mechanism of the transport module is used to repeatedly inject and aspirate dye solution, alcohol, water, buffer solution and transparent solution into the sedimentation bin of the preparation module to complete the staining and transparency of the cells.
Citation Information
Patent Citations
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