A pathological section staining device based on advanced fluid control technology

Abstract

The application relates to the field of pathological section dyeing automation, in particular to an automatic device for cytological section dyeing and histological immunohistochemistry and special dyeing based on advanced fluid control technology, which comprises a centrifugal component at the upper part and a section dyeing component at the lower part, the centrifugal component comprises a centrifugal driving component and a matched liquid path component, the section dyeing component comprises a circular or arc-shaped dyeing turntable and a matched traditional dyeing or immunohistochemistry and special dyeing liquid path component. The application does not adopt a traditional transfer mode, such as a pipetting arm, a pipetting gun and the like, which is prone to mechanical failure, a machine is integrated with key function modules such as sample oscillation, centrifugation, section preparation and dyeing, and can automatically complete cytological sample pretreatment and section dyeing operation, and can be compatible with the functions of histological immunohistochemistry and special dyeing, so that the application greatly simplifies complicated steps, improves the functional diversity, efficiency and stability of the equipment, and reduces the maintenance cost of the equipment.

Description

Technical Field

[0001] This invention relates to the field of automated pathological slide preparation and staining, specifically to an automated device for cytological slide preparation and staining, histological immunohistochemistry, and special staining based on advanced fluid control technology. Background Technology

[0002] Clinical pathology can be divided into histopathology and cytopathology. The most common sample preparation method for histology is paraffin sectioning; centrifugation and sedimentation slide preparation, and individual staining are ideal sample pretreatment methods for cytology. Histopathological and cytopathological staining methods include traditional chemical staining, such as HE staining and Papanicolaou staining, as well as special staining, such as immunohistochemistry and other special staining methods. However, traditional manual and later-developed semi-automatic slide preparation and staining processes are cumbersome and inefficient. Most semi-automatic equipment on the market can only perform single histological, cytological, or tissue microarray slide preparation or a single staining function, and cannot perform multiple functions simultaneously or automate the entire process. Traditional sedimentation liquid-based cell preparation and staining semi-automatic processes typically involve multiple independent steps, including sample shaking, transfer, centrifugation, and slide preparation and staining, requiring multiple manual sample transfers, inter-device transfers, and labeling operations. This workflow is not only cumbersome and time-consuming but also prone to human error, leading to inaccurate experimental results.

[0003] Furthermore, traditional methods require multiple instruments, such as shaker transfer machines, centrifuges, slide preparation and staining machines, and immunohistochemical staining machines. This not only increases equipment costs but also occupies a significant amount of laboratory space, and the equipment failure rate is relatively high. Therefore, there is an urgent need in the market for an integrated and automated device and method that can complete the entire process of cytology and histology slide preparation and staining. For large laboratories, high-throughput automated lines are also needed to improve experimental efficiency, reduce operational complexity and costs, minimize equipment space occupation, and lower the failure rate.

[0004] In traditional fluid control applications for in vitro diagnostics, such as transferring sample liquid from one container to another, an intermediate carrier, such as a pipette and disposable pipette tip, is usually used. Because of the need for repeated high-frequency operations and the tolerance of disposable pipette tips, it is easy to cause empty aspiration, missed aspiration, inaccurate quantification, etc., leading to incorrect experimental results.

[0005] Traditional fluid control methods for pathological slide preparation and staining rely on three-axis robotic arms to move pipette tips, needles, and tubing. However, this multi-directional mechanical movement leads to inaccurate positioning, requiring cleaning of components or replacement of disposable consumables like pipette tips after each use to prevent contamination. A single mechanical system can only perform one liquid transfer or one functional action at a time, such as centrifugation, shaking, or pipetting. Integrating a shaking module into an integrated instrument typically involves ultrasonic vibration motors, increasing instrument cost and causing cell sample deformation that can affect diagnosis, resulting in low efficiency. Furthermore, long paths and numerous bends in the tubing can lead to leaks and air leaks, causing errors in liquid addition and aspiration. Therefore, traditional fluid control instruments require frequent maintenance and calibration to ensure stable and reliable operation. However, advanced fluid control methods and technologies can effectively solve these problems. Summary of the Invention

[0006] The purpose of this invention is to provide a pathological slide preparation and staining device based on advanced fluid control technology, so as to solve the problems mentioned in the background art, such as the cumbersome and unstable nature of traditional manual and various semi-automatic slide preparation and staining devices, the need for multiple devices, high manufacturing and use costs, and low efficiency.

[0007] To achieve the above objectives, this invention provides an automated device for pathological slide preparation and staining based on advanced fluid control technology. Its features include: a single integrated, fully automated system for pretreatment of centrifuged and sedimented cytological samples, slide preparation, and staining; the ability to be equipped with optional consumables for installation and use, switching between cytology, histology, tissue microarray, and high-throughput automated line configurations, and adapting to special staining requirements such as immunohistochemistry. Its structure includes an upper centrifugation assembly and a lower slide preparation and staining assembly. The centrifugation assembly includes a centrifugation drive component and an upper centrifugation fluid path component. The slide preparation and staining assembly includes an arc-shaped staining turntable component and an upper staining fluid path component. Several slide preparation and staining units and several waste liquid tanks are arranged on the staining turntable. The liquid after centrifugation is directly poured into the slide preparation and staining assembly or the waste liquid tank below.

[0008] As a preferred embodiment of the present invention, a plurality of centrifugal units are annularly mounted on the outer side of the centrifugal drive component, and the centrifugal unit includes a basket, and a plurality of centrifugal test tubes are disposed inside the basket.

[0009] As a preferred embodiment of the present invention, the upper centrifuge assembly and the lower slide preparation and staining assembly can be controlled by an external motor to move and rotate relative to each other. A lifting plate is installed on the staining turntable, and the lifting plate is located below the centrifuge unit. The lifting plate lifts the centrifuge unit, so that the positions of the slide preparation and staining unit or waste liquid tank and the centrifuge unit correspond one-to-one through positioning, and the centrifuge unit is flipped to directly pour and transfer the liquid in the centrifuge tube into the slide preparation and staining unit or waste liquid tank.

[0010] As a preferred embodiment of the present invention, the centrifuge tube can also serve as a cell sample preservation bottle; a sleeve is added close to the inner wall of the centrifuge tube, the lower end of the sleeve is close to the bottom of the centrifuge tube, and a filter screen is installed thereon, the filter screen is close to the bottom of the centrifuge tube, after sampling, a sampling brush or alternative stirring material is placed on the outside of the sleeve, the tip of the sampling brush or alternative stirring material is facing the bottom of the centrifuge tube; a vibration motor (328) is installed below the centrifuge tube (32), and the two work together to more thoroughly disperse the cell sample.

[0011] As a preferred embodiment of the present invention, the centrifugal liquid circuit component includes a centrifugal test tube dispensing needle, a drive pump, and matching pipes and reagent bottles; the centrifugal test tube dispensing needle is fixed above the centrifugal unit, and the corresponding dispensing position is positioned by rotating the centrifugal drive component through the centrifugal positioning motor.

[0012] As a preferred embodiment of the present invention, the liquid circuit components of the slide staining assembly are of two types: one type is used for traditional cytological staining, such as for Papanicolaou staining and HE staining; the other type is specifically used for immunohistochemistry and special staining (including tissue microarrays) in cytology and histology.

[0013] As a preferred embodiment of the present invention, the conventional staining liquid circuit component includes several liquid addition needles, several waste liquid aspiration needles, matching pipelines and drive pumps, reagent bottles / storage bottles, glass slides, and conventional staining-specific slide preparation chambers.

[0014] As a preferred embodiment of the present invention, a liquid circuit component specifically designed for immunohistochemistry and special staining includes several dedicated antibody reagent bottles and precision dispensing needles, several single-headed or multi-headed immunohistochemistry and special staining aspiration needles, matching tubing and drive pump and reagent bottles / storage bottles, special staining slides, and a slide preparation compartment-dispenser.

[0015] In a preferred embodiment of the present invention, the special staining slide is a slide with a hydrophobic coating separating several slide adhesion areas. The slide preparation chamber-dispenser is installed on the upper part of the special staining slide, and its upper layer is provided with a liquid storage tank, an overflow port, and several flow channels. The diameter and length of the flow channels are designed according to the flow rate. The ends of the flow channels have downward-facing holes, allowing liquid to be dripped onto the slide preparation holes. Excess liquid is discharged through the overflow channel to ensure consistent liquid addition each time. In addition, the suction needle is aligned with the channels to aspirate and remove waste liquid from the corresponding slide preparation holes and the slide preparation chamber-dispenser. The lower end of the drip channel is close to the slide preparation area, which serves to evenly distribute the liquid volume through multiple holes during dripping. The bottom of the slide preparation chamber-dispenser is provided with several steam holes, and a water bath is provided below the slide preparation chamber-dispenser. The adjustable heating liquid generates steam, which enters the upper part of the slide through the steam holes at the bottom of the slide preparation chamber-dispenser, thus keeping the sample warm and moist.

[0016] As a preferred embodiment of the present invention, the reagent bottle of the immunohistochemistry and special staining liquid circuit system is equipped with a piston, which also functions as an injection pump; the reagent bottle is equipped with a single-headed or multi-headed precision dispensing needle, and the immunohistochemistry and special staining liquid circuit system adopts a multi-headed immunohistochemistry and special staining aspiration needle.

[0017] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0018] 1. This pathological slide preparation and staining device, based on advanced fluid control technology, achieves a high degree of integration and automation in the slide preparation and staining process. By integrating key components such as centrifugation components, turntables, centrifugation units, slide preparation and staining plates, and pipetting components, this invention can complete the entire process from sample preparation and centrifugation to slide preparation and staining on a single device, greatly simplifying the cumbersome steps of traditional slide preparation and staining procedures. This not only significantly improves experimental efficiency and reduces operational complexity but also reduces equipment costs and laboratory space occupation, and lowers equipment failure rates. This device can be optionally equipped with different components and consumables to provide cytological, histological, immunohistochemical, and special staining, tissue microarray staining, and high-throughput automated line configurations, meeting different slide preparation and staining functions and improving the versatility of the equipment's functions.

[0019] 2. In this pathological slide preparation and staining device based on advanced fluid control technology, the centrifuge tube also serves as a cell sample preservation solution bottle; gradient density centrifugation and coarse filtration of impurities are performed simultaneously; moreover, cell samples do not require pre-shaking before centrifugation and can be directly loaded onto the machine; after centrifugation, a mechanical vibration motor disperses the sample, which is less expensive than an ultrasonic motor and does not cause cell deformation that would affect staining and morphological results; gradient density centrifugation and coarse filtration of impurities are performed simultaneously. For special staining processes such as immunohistochemistry, samples are added in one step to prepare slides (tissue / cell microarrays) containing multiple regions. This simplified workflow improves efficiency and reduces costs.

[0020] 3. In this pathological slide preparation and staining device based on advanced fluid control technology, the centrifuge motor, in addition to centrifugation, also has a positioning function during liquid addition, completing centrifugation and positioning in one step. The centrifuge motor can be installed above the centrifuge drive component, further reducing the space required for the equipment and lowering its size, complexity, and production costs.

[0021] 4. In this pathological slide preparation and staining device based on advanced fluid control technology, the liquid dispenser pipeline is designed based on advanced fluid control technology, which greatly shortens the liquid path travel. The multi-liquid path design driven by a peristaltic pump improves efficiency. It does not require the commonly used three-axis robotic arm, nor does it require liquid transfer consumables such as pipette tips. Liquid can be directly poured or dripped into the slide preparation chamber. Multiple liquid paths operate simultaneously, which greatly simplifies the complexity of mechanical actions, reduces the accuracy requirements of motors and liquid pumps, and allows users to easily replace tubing. This significantly improves efficiency, enhances the efficiency and stability of the equipment, and also reduces the maintenance and operating costs of the equipment.

[0022] 5. This pathological slide preparation and staining device, based on advanced fluid control technology, features a streamlined production line. The slide preparation and staining assembly is a large-circular streamline structure, allowing for the replacement of slide preparation and staining units without shutting down the centrifugal drive component. This significantly increases the equipment's throughput. Furthermore, it can be equipped with modules for scanning and printing slide barcodes, as well as subsequent mounting and scanning modules, further expanding its throughput and functionality. Attached Figure Description

[0023] Figure 1 This is a schematic diagram of the overall internal structure of the present invention;

[0024] Figure 2 This is a schematic diagram of the centrifugal component structure and motor installation in this invention;

[0025] Figure 3 This is a schematic diagram of the structure of the slide preparation and dyeing assembly with a support plate in the traditional dyeing process of this invention.

[0026] Figure 4 This is a schematic diagram of the slide preparation and staining components for immunohistochemistry and special staining in this invention;

[0027] Figure 5 This is a schematic diagram of the internal structure of the centrifuge tube in this invention;

[0028] Figure 6 This is a schematic diagram illustrating the effect of lifting and pouring the liquid from the centrifuge tube to the slide preparation chamber in this invention.

[0029] Figure 7 This is a schematic diagram illustrating the effect of sample gradient centrifugation and impurity removal in this invention.

[0030] Figure 8This is a schematic diagram illustrating the effect of sample oscillation, dispersion, and transfer in this invention;

[0031] Figure 9 This is a schematic diagram of the slide preparation chamber-dispenser and glass slide structure, as well as the sample solution being added, in this invention;

[0032] Figure 10 This is a cross-section of the tablet preparation compartment-liquid dispenser structure and a schematic diagram of the liquid addition and aspiration processes in this invention;

[0033] Figure 11 This is a schematic diagram of the assembly line configuration in this invention.

[0034] The meanings of the labels in the diagram are as follows:

[0035] 1. Centrifuge assembly; 11. Centrifuge drive component; 101. Centrifuge fluid path component; 102. Centrifuge tube dispensing needle; 2. Slide preparation and staining assembly; 21. Staining turntable; 22. Waste liquid tank; 23. Lifting plate; 201. Traditional staining fluid path component; 202. Immunohistochemistry and special staining fluid path component; 2021. Immunohistochemistry and special staining dispensing needle; 2022. Immunohistochemistry and special staining aspiration needle; 2023. Reagent bottle; 2024. Single-ended precision dispensing needle; 2025. Multi-ended precision dispensing needle; 2026. Piston; 3. Centrifuge unit; 31. Basket; 32. Centrifuge tube; 321. Sleeve; 322. Filter screen; 323, Sampling brush; 324, Gradient density separation solution; 325, Sample cells; 326, Upper impurities; 327, Cell suspension; 328, Vibration motor; 329, Diluent; 4, Slide preparation and staining unit; 5, Glass slides; 51, Traditional staining glass slides; 52, Special staining glass slides; 53, Slide preparation area; 6, Slide preparation chamber; 61, Traditional staining special slide preparation chamber; 62, Slide preparation chamber-dispenser; 621, Liquid storage tank; 622, Overflow outlet; 623, Flow channel; 624, Orifice; 625, Steam vent; 626, Water bath; 7, Centrifuge positioning motor; 8, Staining positioning motor; 9, Lifting motor. Detailed Implementation

[0036] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0037] This invention provides a pathological slide preparation and staining device based on advanced fluid control technology. The device adopts a layered design, such as... Figures 1-11As shown, the device includes an upper centrifugal assembly 1 and a lower slide preparation and staining assembly 2. The centrifugal assembly 1 includes a centrifugal drive component 11 and an upper centrifugal liquid path component. The slide preparation and staining assembly 2 includes an arc-shaped staining turntable component 21 and an upper staining liquid path component. Several slide preparation and staining units 4 and several waste liquid tanks 22 are arranged on the staining turntable 21. The liquid after centrifugation in the centrifugal assembly 1 is directly poured and transferred to the slide preparation and staining assembly 2 or the waste liquid tank 22 below. Through advanced fluid control technology, this invention cleverly combines the centrifugal assembly and the slide preparation and staining assembly, achieving precise control and efficient transfer of the liquid. This layout not only saves space but also makes the entire device more compact and rational. At the same time, the arc-shaped staining turntable design facilitates the arrangement and mechanical movement of the slide preparation and staining units and the waste liquid tank, improving work efficiency. This design allows multiple liquid transfer operations to be completed in one step. After the centrifugation unit completes the centrifugation operation, the liquid can be directly poured and transferred to the slide preparation and staining unit or the waste liquid tank. This process design simplifies the multiple transfer and operation steps in the traditional slide preparation and staining process, which not only improves work efficiency but also reduces the use of consumables and lowers the cost of use. It also helps to improve the consistency and quality of slide preparation.

[0038] The device employs a two-tiered design, with the centrifugation unit located at the top and the slide preparation and staining unit at the bottom. This layout not only saves space but also makes the entire device more compact and efficient. Furthermore, the arc-shaped staining turntable facilitates the arrangement and mechanical movement of the slide preparation and staining units and waste liquid tank, improving work efficiency.

[0039] Several waste liquid tanks are set on the dyeing turntable so that the waste liquid after multiple centrifugations can be directly poured into the designated location, which facilitates the collection and treatment of waste liquid.

[0040] In this embodiment, a plurality of centrifugal units 3 are installed in a ring around the outer side of the centrifugal drive component 11. The centrifugal unit 3 includes a basket 31, and a plurality of centrifugal test tubes 32 are arranged inside the basket 31.

[0041] Specifically, the upper centrifuge assembly 1 and the lower slide preparation and staining assembly 2 can be controlled by external motors for relative vertical movement and rotational positioning. These external motors include a centrifuge positioning motor 7, a staining positioning motor 8, and a lifting motor 9. The staining positioning motor 8 controls the rotational positioning, ensuring a one-to-one correspondence between the slide preparation and staining unit 4 or the waste liquid tank 22 and the centrifuge unit 3. A lifting plate 23 is installed on the staining turntable 21, located below the centrifuge unit 3. The relative vertical movement of the centrifuge assembly 1 and the slide preparation and staining assembly lifts the centrifuge unit 3, causing it to flip and directly pour the liquid from the centrifuge tube into the slide preparation and staining unit 4 or the waste liquid tank 22. After centrifugation by the centrifuge drive assembly 1, the liquid is directly poured into the slide preparation and staining assembly 2 or the waste liquid tank 22 below. In addition to centrifuging the sample, the centrifuge drive assembly 1 also functions to agitate and disperse the sample by shaking or vibrating the motor 328.

[0042] Furthermore, the centrifuge tube 32 can also serve as a cell sample preservation bottle. A sleeve 321 is attached to the inner wall of the centrifuge tube 32, with the lower outlet of the sleeve 321 near the bottom of the centrifuge tube 32. A filter 322 is installed on the sleeve 322, which is also near the bottom of the centrifuge tube 32. During sampling, a sampling brush is placed outside the sleeve 321, with the tip of the sampling brush 323 or an alternative stirring medium (such as an appropriately sized pipette tip) facing the bottom of the centrifuge tube. A vibration motor 328 is installed below the centrifuge tube 32. The two components work together to shake and stir, better dispersing and suspending the cell sample. Before centrifugation, a gradient density separation solution is added and slowly introduced into the bottom of the centrifuge tube 32 from the sleeve 321, ensuring that most of the suspended cells are in the upper part of the separation solution. After centrifugation and shaking, diluent or buffer solution is added to ensure the cell sample is fully suspended and evenly distributed.

[0043] Furthermore, the centrifugal liquid circuit component includes a centrifuge tube dispensing needle, a drive pump, and matching pipes and reagent bottles; the centrifuge tube dispensing needle is fixed above the centrifugation unit 3, and the centrifugation drive component 11 is rotated by the centrifugation positioning motor 7 to position the corresponding dispensing position.

[0044] Furthermore, the liquid path components of the slide preparation and staining assembly 2 are divided into two types: one type is used for conventional staining, such as Papanicolaou staining and HE staining; the other type is used specifically for immunohistochemistry and special staining.

[0045] Furthermore, the slide preparation and staining unit 4 includes slide preparation chambers 6, each containing glass slides 5. There are two types of slide preparation chambers 6: a conventional staining slide preparation chamber 61 and a special staining slide preparation chamber-dispenser 62 specifically for immunohistochemistry and other special staining processes. The glass slides are divided into two main categories: conventional staining slides 51 and special staining slides 52 used for immunohistochemistry and other processes.

[0046] Furthermore, the traditional staining circuit component 201 includes several injection needles, several waste injection needles, matching tubing, a drive pump, and reagent bottles / reservoir bottles. Furthermore, the immunohistochemistry and special staining dedicated circuit component 202 includes several dedicated antibody reagent bottles 2023, single-ended precision injection needles 2024, and multi-ended precision injection needles 2025; several immunohistochemistry and special staining aspiration needles 2022, and several injection needles 2021; other matching tubing, a drive pump, and reagent bottles / reservoir bottles; the antibody reagent bottle 2023 has a piston 2026 inside, which can also be used as an injection pump.

[0047] Furthermore, the liquid addition drive pump of the centrifugal liquid circuit component 101, as well as the liquid addition drive pump and waste liquid suction drive pump of the traditional dyeing liquid circuit component 201, are all sampling quantitative peristaltic pumps, which are lower in cost and designed to make it easy for users to replace the tubing.

[0048] Furthermore, the immunohistochemistry and special staining slides 52 have a hydrophobic coating that separates several slide adhesion areas 53. The slide preparation compartment-dispenser 62 has a liquid storage tank 621, an overflow outlet 622, and several flow channels 623 on its upper layer. The diameter and length of the flow channels 623 are set according to the flow rate. The ends of the flow channels 623 have downward-facing orifices 624, with the lower outlet of the orifices 624 directly facing the slide preparation area 53, serving to evenly distribute the liquid during dispensing. The bottom of the slide preparation compartment-dispenser 62 has several steam holes 625, and a water bath 626 is located below it. The water temperature is controllable and can be conducted to the immunohistochemistry and special staining slides 52 and the samples. Steam in the water bath can enter the interior of the slide preparation compartment-dispenser 62 through the steam holes at the bottom of the slide preparation compartment-dispenser 62, serving to keep the samples warm and moist.

[0049] Furthermore, the slide preparation and staining component 2 of the present invention can be designed as a large annular production line structure, with more slide preparation and staining units 4 installed, and the slide preparation and staining units 4 can be replaced up and down without stopping the centrifuge; to further expand the throughput and functions, it can also be equipped with scanning and printing glass slide barcode functions, subsequent sealing and scanning functions, etc.

[0050] The pathological slide preparation and staining device based on advanced fluid control technology of the present invention includes the following steps during use:

[0051] 1. Taking cell preparation and traditional staining – standalone protocol as an example:

[0052] S1. Sample and slide preparation: When sampling, place the sampling brush on the outside of the sleeve, with the tip of the sampling brush or the alternative stirring material facing the bottom of the centrifuge tube. Manually place the cell preservation solution bottle / centrifuge tube, install the filter, and install the slide and slide preparation compartment to the designated position.

[0053] S2. Cell sample shaking and centrifugation: Shake the centrifuge tube by rotating the centrifuge drive component back and forth to break up the cells in the tube; add the separation solution through the liquid addition device above, slowly entering from the bottom of the centrifuge tube, and start the centrifuge positioning motor to centrifuge;

[0054] S3. Sample transfer and sedimentation preparation: Lift the staining plate and pour the upper centrifugation waste liquid into the waste liquid tank; add diluent to the centrifuge tube through the liquid addition device above, start the vibration motor to shake the centrifuge tube, and use a cervical brush or stirring material to disperse the sample into a cell suspension state.

[0055] S4. Sedimentation Preparation: The cell suspension sample in the centrifuge tube is poured into the preparation chamber below by raising the preparation staining plate. It is left to stand for a certain period of time to allow the cells to settle and adhere to the glass slide.

[0056] S5. Traditional staining of cell slides (Papanicolaou staining or HE staining, etc.): Remove waste liquid with a waste liquid aspiration needle, set the program according to the reagent instructions, add staining solution and rinsing solution and remove waste liquid. In the last step, the slide will be kept at a certain humidity to prevent the slide from drying out.

[0057] S6. Remove the stained slides from the slide preparation chamber for subsequent sealing, scanning, or observation.

[0058] 2. Cellular slide immunohistochemical staining - standalone protocol as an example:

[0059] S1. Sample and slide preparation: When sampling, place the sampling brush on the outside of the sleeve, with the tip of the sampling brush or the alternative stirring material facing the bottom of the centrifuge tube. Manually place the cell preservation solution bottle / centrifuge tube, install the filter, install the slide, and select a suitable immunohistochemistry slide preparation compartment-dispenser to install it in the designated position.

[0060] S2-S4 are the same as the steps corresponding to 1 above;

[0061] S5. Immunohistochemical staining of cell slides: Turn on the water bath in advance and set the temperature according to the reagent instructions; remove the waste liquid on the slide using the waste liquid aspiration needle; set the procedure according to the reagent instructions, such as: add the primary antibody reagent using the reagent bottle and single-ended precision dispensing needle, incubate at constant temperature and humidity, add washing solution and remove the waste liquid using a multi-ended precision dispensing needle, add the secondary antibody reagent using the reagent bottle and multi-ended precision dispensing needle, incubate at constant temperature and humidity, add washing solution and remove the waste liquid. In the last step, the slide will be kept at a certain humidity to prevent the slide from drying out.

[0062] S6. Remove the stained slides from the slide preparation compartment-liquid dispenser for subsequent sealing, scanning, or observation.

[0063] 3. Histological immunohistochemical staining (using a standalone protocol as an example):

[0064] S1. Prepare slides manually according to the experimental procedure beforehand: such as sample dehydration, embedding, sectioning, bleaching, retrieval, baking, dewaxing, rehydration, antigen retrieval, etc. Precautions for slides and retrieval: Adhesive, non-detachable slides should be used. The slides should have a waterproof coating and be divided into several areas; during retrieval, the tissue section sample must fall within the adhesive area of ​​the waterproof isolation zone on the slide.

[0065] S2-S6 are the same as the steps corresponding to 2 above.

[0066] Finally, it should be noted that the electronic components in the centrifugal positioning motor 7 and other components in this embodiment are all general standard parts or parts known to those skilled in the art. Their structures and principles can be learned by those skilled in the art through technical manuals or conventional experimental methods. In the idle parts of this device, all the above-mentioned electrical components are connected by wires. The specific connection method should refer to the working order of each electrical component in the above working principle to complete the electrical connection. All of these are technologies known in the art. The centrifugal liquid circuit component includes pipe fittings connecting the centrifuge test tube liquid addition needle and the three-way valve, as well as reagent bottles / storage bottles; the staining liquid circuit component includes pipe fittings connecting the liquid addition needle, the liquid aspiration needle, and the staining needle, as well as reagent bottles / storage bottles and waste bottles. All of the above-mentioned components are general standard parts or parts known to those skilled in the art. Their structures and principles can be learned by those skilled in the art through technical manuals or conventional experimental methods. In the idle parts of this device, all the above-mentioned components are connected by pipes. The specific connection method should refer to the working order of each component in the above working principle to complete the physical connection. All of these are technologies known in the art.

[0067] The foregoing has shown and described the basic principles, main features, and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The embodiments and descriptions in the specification are merely preferred examples and are not intended to limit the invention. Various changes and modifications can be made to the invention without departing from its spirit and scope, and all such changes and modifications fall within the scope of the claimed invention.

Claims

1. A pathological slide preparation and staining device based on advanced fluid control technology, comprising an upper centrifugation assembly (1) and a lower slide preparation and staining assembly (2), characterized in that: The centrifuge assembly (1) includes a centrifuge drive component (11) and an upper centrifuge liquid path component (101). The slide preparation and staining assembly (2) includes an arc-shaped staining turntable (21) and an upper staining liquid path component. Several slide preparation and staining units (4) and several waste liquid tanks (22) are arranged on the staining turntable (21). The liquid after centrifugation by the centrifuge assembly (1) is directly poured and transferred to the slide preparation and staining assembly (2) or the waste liquid tank (22) below. Several centrifuge units (3) are installed in a ring on the outside of the centrifuge drive component (11). The centrifuge unit (3) includes a basket (31). Several centrifuge tubes (32) are arranged inside the basket (31). The upper centrifuge assembly (1) and the lower slide preparation and staining assembly (2) can be moved up and down relative to each other and rotated and positioned by an external motor, so that the slide preparation and staining unit (4) or waste liquid tank (22) and the centrifuge unit (3) are in a one-to-one correspondence.

2. The pathological slide preparation and staining device based on advanced fluid control technology according to claim 1, characterized in that: The staining turntable (21) is equipped with a lifting plate (23) and is located below the centrifuge unit (3); the lifting plate (23) lifts the centrifuge unit (3) by moving up and down relative to each other, and the centrifuge unit (3) flips over to directly pour the liquid in the centrifuge tube (32) into the slide staining unit (4) or the waste liquid tank (22).

3. The pathological slide preparation and staining device based on advanced fluid control technology according to claim 1, characterized in that: The centrifuge tube (32) can also serve as a cell sample preservation bottle; a sleeve (321) is attached to the inner wall of the centrifuge tube (32), the lower outlet of the sleeve (321) is close to the bottom of the centrifuge tube (32), and a filter screen (322) is installed thereon. The filter screen (322) is close to the bottom of the centrifuge tube (32). After sampling, a sampling brush (323) or a substitute stirring material is placed outside the sleeve (321), and the tip of the sampling brush (323) or the substitute stirring material is facing the bottom of the centrifuge tube; a vibration motor (328) is installed below the centrifuge tube (32).

4. The pathological slide preparation and staining device based on advanced fluid control technology according to claim 1, characterized in that: The centrifugal liquid circuit component (101) includes a centrifugal test tube liquid injection needle (102), a drive pump and matching pipes and reagent bottles, and a centrifugal positioning motor (7). The centrifugal test tube liquid injection needle (102) is fixed above the centrifugal unit (3). The centrifugal positioning motor (7) is installed below or above the centrifugal drive component (11). The centrifugal positioning motor (7) rotates the centrifugal drive component (11) to position the corresponding liquid injection position.

5. The pathological slide preparation and staining device based on advanced fluid control technology according to claim 1, characterized in that: The staining solution components of the slide preparation and staining assembly (2) are divided into two types: including traditional staining solution components (201) and immunohistochemistry and special staining solution components (202).

6. The pathological slide preparation and staining device based on advanced fluid control technology according to claim 5, characterized in that: The conventional staining liquid circuit component (201) includes several liquid addition needles, several waste liquid aspiration needles, matching pipelines, drive pumps and reagent bottles / storage bottles, slide preparation and staining unit (4) and conventional staining special slide preparation chamber (61).

7. The pathological slide preparation and staining apparatus based on advanced fluid control technology according to any one of claims 5 or 6, characterized in that: The immunohistochemistry and special staining liquid path component (202) includes several immunohistochemistry and special staining dispensing needles (2021), several immunohistochemistry and special staining aspiration needles (2022), several dedicated antibody reagent bottles (2023), several single-head precision dispensing needles (2024), and several multi-head precision dispensing needles (2025); the slide preparation and staining unit (4) includes special staining glass slides (52), slide preparation chamber-dispenser (62), matching pipelines, drive pump and reagent bottles.

8. The pathological slide preparation and staining device based on advanced fluid control technology according to claim 7, characterized in that: The slide preparation chamber-liquid dispenser (62) functions to distribute the liquid evenly to the slide preparation area (53) when it drips liquid. It is placed on the upper part of the special staining glass slide (52). The upper layer is provided with a liquid storage tank (621), an overflow outlet (622) and several flow channels (623). The diameter and length of the flow channels (623) are set according to the required flow rate. The end of the flow channel (623) has a downward drip channel (624), and its lower end is close to the slide preparation area (53).

9. The pathological slide preparation and staining device based on advanced fluid control technology according to claim 7, characterized in that: The immunohistochemistry and special staining solution circuit component (202) has a piston (2026) installed in the antibody reagent bottle (2023), which also serves as an injection pump; the antibody reagent bottle (2023) is equipped with a single-headed precision injection needle (2024) or a multi-headed precision injection needle (2025).

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