A natural sedimentation type liquid-based cell preparation and single cylinder pathological staining device

Abstract

This invention discloses a natural sedimentation liquid-based cell preparation and single-cylinder pathological staining device, belonging to the field of pathological automation technology. The device includes a slide preparation unit, a staining unit, and connecting components. The slide preparation unit has both centrifugation-free and centrifugation modes. Cell enrichment is completed without centrifugation in a capless preservation bottle. Pushing the slide against its drain valve allows for directional and quantitative transfer of sample solution and cell sedimentation without opening the cap. After slide preparation, a pusher horizontally pushes the slides one by one into a slide holder, which then flips to a vertical position and descends into the single-cylinder staining tank. The staining unit / device uses a bidirectional liquid pump and a bidirectional liquid valve to control the alternating extraction and release of different reagents, completing multi-step sample staining within a single tank. This invention eliminates traditional methods such as robotic arm liquid transfer or slide transfer, and individual slide staining, employing advanced fluid control technology to significantly improve the efficiency of slide preparation and staining, while reducing manufacturing and usage costs.

Description

Technical Field

[0001] This invention relates to the field of pathological slide preparation and staining technology, specifically to an advanced fluid-controlled natural sedimentation liquid-based cell slide preparation technology and an automated single-cylinder immersion staining device, including improved consumables, reagents, and automation equipment. Background Technology

[0002] Clinical pathology is divided into cytopathology and histopathology. Its pre-diagnostic processing mainly includes slide preparation and staining. Gradient density centrifugation sedimentation separation technology is an ideal slide preparation method for cytopathology, involving multiple independent steps, including sample shaking, transfer, centrifugation, and slide preparation. This process requires manual transfer of samples between devices multiple times, making it cumbersome. Common semi-automatic traditional methods also require multiple instruments, such as shaking transfer machines, centrifuges, slide preparation and staining machines, and the instruments require repeated replacement of disposable pipette tips. Because the slides are in a dispersed, horizontal state after preparation, staining can only be done individually or in groups using drop staining. Low liquid pressure difference and insufficient permeability result in staining effects that are inferior to immersion staining, leading to very low efficiency. For example, the technology disclosed in "A Pathological Slide Preparation and Staining Device Based on Advanced Fluid Control Technology" (202411992108.3) solves the problem of low sample transfer efficiency in similar centrifugation sedimentation slide preparation equipment, but it does not solve the problems of low staining and overall efficiency.

[0003] In addition, traditional cell and tissue pathology staining machines use a multi-cylinder immersion method, requiring slide holders to be transferred from one staining cylinder to another multiple times. As a result, the instruments are inefficient, bulky, and consume large amounts of reagents, making them unsuitable for small-batch special staining or intraoperative frozen section staining. Furthermore, there is no automatic impurity separation device when reusing reagents, requiring frequent replacement of new reagents and resulting in waste.

[0004] In summary, traditional cytopathology slide preparation machines and pathology staining machines suffer from drawbacks such as low efficiency, large size, frequent malfunctions, high production and operating costs, and a high frequency of maintenance required by the manufacturer. However, advanced fluid control technology, coupled with complementary sample pretreatment and suitable slide adhesion techniques, can effectively solve these problems and facilitate full-process automation and high throughput. Summary of the Invention

[0005] The purpose of this invention is to provide a natural sedimentation liquid-based cell slide preparation and single-cylinder pathological staining device to solve the shortcomings of traditional cell pathological slide preparation and pathological staining machines mentioned in the background art, such as low efficiency, frequent failures, and high production and use costs.

[0006] The slide preparation unit of the present invention includes a slide preparation unit, a staining unit, and a connecting component between the two. After the sample solution is prepared in the slide preparation unit, the connecting component automatically transfers the slide to the staining unit. The slide preparation unit includes two modes: centrifugation-free slide preparation (mode 1) and centrifugation sedimentation slide preparation (mode 2). The staining unit can also be used independently as an immersion staining device for single-cylinder pathological sections.

[0007] 1. In slide preparation method 1, the traditional centrifugation pretreatment method is replaced. The slide preparation unit includes a pre-filled modified cell preservation solution, pretreatment materials, and a capless preservation solution bottle. The pretreatment materials can adsorb / filter impurities. Mechanical vibration of the preservation solution bottle causes heavier abnormal cells to detach and settle, achieving the enrichment of abnormal cells. This capless preservation solution bottle allows sample solution to be transferred without opening the cap: a drain valve is provided between the bottle body and the cap; the flow path of the sample solution includes several spaces formed between the bottle body, the cap, and the drain valve. The valve stem and valve disc of the drain valve are a flexible, integrated structure, with the edge of the valve disc fixed between the bottle body and the cap; under the pushing force of the valve stem, the inlet and outlet can be moved to the open state.

[0008] Furthermore, the valve stem protrudes outside the storage liquid bottle to form its pressure-bearing end, and its extension trajectory is in the shape of a weir, with the liquid outlet located on its weir wall; during liquid discharge, the glass slide pushes and presses the pressure-bearing end at a set position, forming a fixed-volume sealed space together with the weir, thereby limiting the amount and position of liquid discharged each time it is pushed.

[0009] Furthermore, in the centrifugation-free slide preparation unit described in slide preparation form 1, a preservation liquid bottle tray is provided, and a glass slide guide tray is provided below it, both of which can rotate under the drive of a motor; several of the cap-free preservation liquid bottles are placed in fixed positions on the preservation liquid bottle tray, with the valve stem and pressure-bearing end of the drain valve facing downwards; several glass slides are placed on the glass slide guide tray, and are fixed in a one-to-one correspondence with the positions of the cap-free preservation liquid bottles above.

[0010] Furthermore, in slide preparation form 1, a pressure plate is provided above the preservation solution bottle. When the pressure plate is activated to press down on the preservation solution bottle, the valve stem is pushed up by the glass slide to the open state of the drain valve, and the sample solution is transferred to the set position on the glass slide; the cells are allowed to settle naturally for a set time and adhere to the glass slide; conversely, when the pressure plate is lifted upward, the capless preservation solution bottle and its valve stem leave the corresponding glass slide; the drain valve returns to the normally closed state.

[0011] Furthermore, in slide preparation form 1, a vibration motor that can be linked to a centrifugation-free preservation bottle is installed on the slide preparation unit. The motor is activated when the sample flows out and settles to promote cell detachment from the bottle and uniform distribution, and finally adheres to the glass slide.

[0012] 2. In slide preparation type 2, the traditional pre-centrifugation method is retained, especially for samples requiring strict pre-treatment. Its features include: a centrifuge turntable at the top of the slide preparation unit and a slide guide tray below; pre-opened centrifugation preservation solution bottles are mounted on the turntable. After centrifugation, a lower pusher rotates the centrifugation preservation solution bottle outwards to dispose of waste liquid; an upper pusher rotates the centrifugation preservation solution bottle inwards to pour the sample liquid into the corresponding slide preparation chamber below for natural sedimentation.

[0013] In slide preparation method 2, the centrifugal slide preparation unit, as disclosed in the technology of "A Pathological Slide Preparation and Staining Device Based on Advanced Fluid Control Technology" (202411992108.3), adopts a method of transferring sample liquid by tilting the preservation liquid bottle after centrifugation. A centrifuge turntable is set above, and a fixed liquid path and liquid inlet are set above the preservation liquid bottle. Other different features are: a glass slide guide tray is set below, both of which can be rotated under the drive of a motor; the centrifugal preservation liquid bottle with its cap already opened is mounted on the centrifuge turntable through the lugs on both sides; several glass slides are placed on the glass slide guide tray, and their positions correspond one-to-one with the preservation liquid bottle; each glass slide is equipped with a slide preparation chamber to help with sample positioning; several push rods are set above and below the outer side of the centrifugal preservation liquid bottle; after sample centrifugation, the lower push rod pushes the centrifugal preservation liquid bottle to rotate, and when the bottle mouth is outward, the waste liquid is poured into the waste liquid tank; the upper push rod pushes the centrifugal preservation liquid bottle to rotate, and when the bottle mouth is inward, the sample liquid is poured into the corresponding slide preparation chamber below, and naturally settles for a set time to allow the cells to adhere to the corresponding glass slide.

[0014] Furthermore, in slide preparation type 2, the centrifugal preservation liquid bottle of the centrifugal slide preparation unit is equipped with a hanging ear, and the centrifugal turntable is equipped with a hanging ear slot for the preservation liquid bottle. The centrifugal motor is installed above the centrifugal turntable and also serves as the turntable positioning motor. The centrifugal preservation liquid bottle with the cap already opened is installed on the hanging ear slot of the preservation liquid bottle through the hanging ear and is swung outward when the centrifugal turntable rotates. The slide preparation tray can drive all slide preparation chambers to move up and down. During slide preparation, the slide preparation chambers are pressed down to press the slides tightly. Conversely, after the slide preparation is completed, all slide preparation chambers are lifted. Furthermore, in slide preparation method 2, several waste liquid dispensing levers and sample dispensing levers are respectively installed at different positions above and below the centrifugation preservation solution bottle; after sample centrifugation, the waste liquid dispensing lever pushes the mouth of the centrifugation preservation solution bottle to rotate to one side, and the waste liquid is poured into the waste liquid tank; the centrifuged sample is diluted with buffer solution, and the vibration motor linked to the preservation solution bottle is activated to disperse the sample cells; the turntable motor is activated to position the preservation solution bottle sequentially to the corresponding sample dispensing lever, and the sample dispensing lever pushes the mouth of the centrifugation preservation solution bottle to rotate to the other side, and the sample solution is poured into the corresponding slide preparation chamber below, allowing the cells to settle and adhere to the corresponding glass slide; then, the flushing system is activated, and the slide preparation chamber tray is raised.

[0015] 3. The staining unit in this invention can be used independently for staining pathological sections without relying on other components of this invention. The staining unit includes a single staining tank, a slide holder, and a liquid system. Staining is completed by alternating pumping and releasing of liquid in a single staining tank, eliminating the need to transfer slides between multiple staining tanks. The staining tank is connected to a bidirectional liquid pump, and the other end of the bidirectional liquid pump is connected to a bidirectional liquid valve group. The bidirectional liquid valve group is connected to corresponding reagent bottles, such as Papanicolaou staining buffer, ethanol, hematoxylin, EAOG, and waste bottles, through multiple pipes, realizing bidirectional transfer of reagents from the staining tank to the liquid bottle.

[0016] Furthermore, in the dyeing unit, the dyeing cylinder is equipped with several liquid level sensors to control the liquid level to a set height; the inlet and outlet of the liquid bottle are located in the middle of the liquid bottle, and a drain switch is provided at the bottom of the liquid bottle for periodic cleaning of sediment.

[0017] 4. The connecting component in this invention connects the slide preparation unit and the staining unit to achieve full automation of the slide preparation and staining processes. The connecting component includes a slide pusher component and a slide holder lifting and flipping component.

[0018] Furthermore, before transferring the slides, the slide guide tray is rotated and positioned, and the slide holder is raised and lowered to position itself, so that the guide grooves of the slide guide tray, the staining vat slide guide groove, and the slide holder slot are aligned in a straight line. The slide pusher pushes the slide into the slide holder slot along the two guide grooves until it reaches its end. The above actions are repeated one by one until the last slide.

[0019] Furthermore, the center of gravity of the slide holder and its rotatable lifting beam connection point have a horizontal positional difference before startup. After loading is completed, the flipping component is automatically triggered, and the slide holder's own gravity is used to automatically restore its center of gravity and its lifting beam connection point to vertical alignment. The slide holder flips from a horizontal slide receiving state to a vertical state, and then the slide holder descends to the staining position in the vat.

[0020] 5. In slide preparation methods 1 and 2, the slides used must have sufficient adhesion to the cells; the cell preservation solution used must be compatible with the slides to ensure that the preservation solution does not impair the adhesion of the slides; the cell preservation solution used in the centrifugation-free slide preparation method is sufficient to dissolve impurities such as red blood cells and protein mucus.

[0021] Furthermore, the slide guide tray is provided with a flushing channel on the inner side, with a flushing pipeline system and its outlet at the upstream, a slide guide in the middle, and a waste liquid tank at the downstream. After the sample liquid has settled naturally, the flushing system is turned on at regular intervals to flush away cells and impurities outside the set range and those that are not attached to the slide.

[0022] Technical effects of the invention: 1. This invention can quickly and conveniently achieve full automation of cell sample pretreatment, slide preparation and staining, and eliminates traditional pipetting arms, disposable pipette tips and other transfer methods that are prone to mechanical failure, which greatly reduces the manufacturing cost, use cost and maintenance cost of consumables and equipment of similar products.

[0023] 2. The centrifugation-free natural sedimentation liquid-based cell preparation technology of the present invention greatly improves efficiency while ensuring the quality of the prepared slides; the single-cylinder pathological staining technology of the present invention abandons the multi-cylinder transfer and immersion mode, improves staining efficiency, greatly reduces the size of the equipment, and is also suitable for small-batch special pathological staining, greatly saving reagents, and the reagents can be reused and impurities can be removed.

[0024] 3. The two technologies of this invention can be flexibly combined to meet the needs of different scenarios. For example, the two technologies can be combined to automate the preparation and staining of liquid-based cell slides by natural sedimentation, overcoming the low-throughput drip staining mode after the past automated liquid-based cell slide preparation, realizing batch automated staining, and greatly improving staining quality and efficiency.

[0025] 4. The single-cylinder pathological staining slide holder of this invention uses an innovative flat-push transport and gravity flipping structure, combined with a turntable, which can be easily expanded to a platform for front-end coding, back-end mounting and scanning, and AI slide reading, providing a solid hardware foundation for the intelligentization of the entire pathology process. Attached Figure Description

[0026] Figure 1 This is a structural diagram of the sedimentation-type, centrifugation-free, liquid-based cell preparation and staining integrated machine of the present invention; Figure 2 This is a structural diagram of the sample transfer structure of the capless preservation bottle of the present invention; Figure 3 This is an exploded view of the integrated machine of the present invention - centrifuge-free form 1; Figure 4 This is a structural diagram of the single-cylinder pathological staining device of the present invention; Figure 5A This is a structural diagram of the dyeing unit of the integrated machine of the present invention; Figure 5B This is a structural diagram showing the loading and lowering of the glass slide holder in the staining unit of the present invention; Figure 5C This is a structural diagram of the glass slide holder of the staining unit of the present invention rising and turning vertical; Figure 6 This is a structural diagram of the overall structure of the film preparation unit of the present invention - centrifugal form 2; Figure 7 This is a diagram showing the centrifugal turntable installation structure of the film-making unit type 2 of the present invention; Figure 8This is a diagram showing the installation structure of the film preparation compartment tray in form 2 of the present invention.

[0027] Labels: 1. Slide preparation unit; 2. Staining unit; 101. Bottle pressing plate; 102. Slide guide tray; 103. Slide; 104. No-opening preservation solution bottle; 1041. Preservation solution bottle body; 1042. Preservation solution bottle cap; 1043. Drain valve; 1044. Valve stem and pressure bearing end; 1045. Inlet; 1046. Outlet; 1047. Valve disc; 1048. Dike; 105. Preservation solution bottle tray; 1051. Preservation solution bottle tray hole seat; 1052. Positioning pin hole; 106. Waste liquid tank; 107. Bottle pressing plate vibration motor; 108. Bottle pressing motor; 109. Slide push rod; 110. Push rod motor A; 111. Slide tray motor; 112. Flushing pipeline system; 113. Flushing flow channel; 114. Tray positioning pin; 121. Centrifuge turntable; 1211. Preservative solution bottle hanger slot; 1212. Centrifuge vibration motor; 122. Centrifuge turntable motor; 123. Turntable motor mounting plate; 124. Centrifuge preservation solution bottle; 1241. Preservative solution bottle hanger; 1242. Inward pouring of sample solution; 1243. Outward pouring of waste liquid; 125. Centrifuge buffer solution inlet; 126. Separation solution inlet; 127. Slide preparation tray; 1271. Slide preparation tray hole and lock 128. Slide Compartment; 1281. Slide Compartment Lock; 129. Waste Liquid Discharge Push Rod; 130. Push Rod Motor B; 131. Sample Discharge Push Rod; 132. Push Rod Motor C; 141. Screw Positioning Pin; 142. Positioning Pin Spring; 143. Tray Push-Top Drive Assembly; 144. Tray Lifting Positioning Rod; 201. Slide Holder; 2011. Slide Holder Slot; 202. Staining Cylinder; 2021. Liquid Level Sensor; 203. Buffer Pump; 2031. Buffer pump - buffer valve piping; 2032. Buffer pump inlet connector; 204. Bidirectional liquid pump; 2041. Bidirectional liquid pump - liquid valve assembly piping; 2042. Bidirectional liquid pump - staining tank piping; 205. Buffer valve; 206. Bidirectional liquid valve assembly; 207. Reagent liquid multi-port connector; 2071. Reagent connector; 208. Buffer valve - staining tank piping; 209. Buffer valve - flushing system piping; 210. Slide holder lifting beam; 2101. Connection between slide holder and lifting beam; 211. Slide holder lifting beam hanging groove; 212. Slide holder horizontal lock; 213. Staining tank slide guide groove; 214. Slide holder lifting drive assembly; 220. Waste liquid discharge valve; 221. Staining tank drain pipe; 222. Waste liquid discharge pipe. Detailed Implementation

[0028] 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.

[0029] The pathological slide preparation and staining apparatus of the present invention mainly includes core technology modules such as centrifugation-free cell slide preparation, centrifuged cell slide preparation, single-cylinder pathological staining and their connection system, which can be used individually or in combination into different forms.

[0030] Example 1: Application of centrifugation-free cell slide preparation technology module and centrifugation-free cell slide preparation machine Combining the technical module structure and working principle of the centrifugation-free cell slide preparation unit (1) (Form 1) Figures 1 to 3 The slide preparation unit (1) is equipped with a slide guide tray (102), which is driven to rotate and be positioned by a slide tray motor (111) below it. Several slides (103) are placed on the slide guide tray (102). A preservation liquid bottle tray (105) is provided above it. The preservation liquid bottle tray (105) is positioned and can move freely up and down by the positioning pin (1052) of the elastically retractable tray positioning pin (114). The preservation liquid bottle cap (1042) is equipped with a drain valve (1043). The preservation liquid bottle (104) is inserted into the preservation liquid bottle tray hole seat (1051) without opening the cap. A bottle pressing plate (101) is provided on the top of the bottle pressing plate, which is driven to lift and lower by a bottle pressing motor (108). A bottle pressing plate vibration motor (107) is installed on the bottle pressing plate (101).

[0031] The centrifugation-free slide preparation unit (Form 1) can be implemented independently as a liquid-based cell slide preparation machine. Its usage process is as follows: the capless preservation liquid bottle (104) is pre-filled with adsorption / filtration material and pre-filled with the improved formula of cell preservation liquid; after the doctor takes a sample, the sampling brush is placed in the body of the preservation liquid bottle (1041), the cap of the preservation liquid bottle (1042) is tightened, and the preservation liquid bottle is sent to the laboratory for testing; several glass slides (103) are placed in the guide groove of the glass slide guide tray (102); the capless preservation liquid bottle (104) is inserted into the hole seat (1051) of the preservation liquid bottle tray without opening the cap, and then the entire preservation liquid bottle rack (105) is placed above the glass slide guide tray (102), and the positioning pin hole (1052) is aligned with the tray positioning pin (114), corresponding one-to-one with the position of the glass slide and the preservation liquid bottle below. After placement, start the bottle pressing motor (108). The bottle pressing plate (101) pushes the capless preservation solution bottle (104) downwards. The valve stem and pressure-bearing end (1044) at the bottom of the drain valve (1043) are pushed by the glass slide (103), causing the valve disc (1047) to undergo elastic deformation, which drives the inlet (1045) and outlet (1046) to move to the open state. The sample solution flows into the containment dam (1048) in a directional and quantitative manner, and the cells settle on the glass slide (103). Start the bottle pressing plate vibration motor (107); stay for a set time to allow the cells to settle and adhere to the set position on the glass slide naturally; turn on the flushing system to flush away impurities outside the set range and those that have not adhered, start the bottle pressing motor (108) to lift the preservation solution bottle rack, and at the same time, the drain valve (1043) returns to the normally closed state; the slide preparation is completed, and the glass slide (103) can be manually removed and transferred to the slide rack for the next staining step.

[0032] Example 2: Application of the centrifuged cell slide preparation technology module and centrifuged cell slide preparation machine The centrifugation slide preparation unit (1) (Form 2) is specifically designed for samples requiring rigorous pre-centrifugation treatment. Its structure and working principle are combined... Figures 6 to 8The centrifuge disc motor (122) drives the centrifuge disc (121) to rotate at high speed, while also enabling precise positioning at low speed. It is suspended from the top of the unit via a disc motor mounting plate (123), leaving more space below for other components. A centrifuge vibration motor (1212) is installed on the centrifuge disc (121). The open centrifuge preservation bottle (124) also functions as a centrifuge tube. It has preservation bottle hanging ears (1241) on both sides, which can be inserted into the preservation bottle hanging ear slots (1211) on the outside of the centrifuge disc (121) to suspend it and allow it to swing in and out (similar to the basket of a regular centrifuge). Additionally, sample liquid (1242) can be poured inwards, and waste liquid (1243) can be poured outwards. Several fixed liquid channels and inlets are provided above the centrifuge preservation bottle (124), such as a centrifuge buffer inlet (125) and a separation liquid inlet (126). The opening and closing control methods of the slide preparation compartment (128) and the slide (103) are as follows: the slide preparation compartment (128) is locked and fixed by the slide preparation compartment latch (1281) and the slide preparation compartment tray (127) tray hole and latch (1271); the slide (103) is positioned by the guide groove of the slide guide tray (102) and can slide outward in the guide groove; the slide preparation compartment tray (127) and the slide guide tray (102) are connected and fixed by the screw positioning pin (141) to fix their horizontal relationship, and the positioning pin spring (142) on the screw positioning pin (141), together with the tray push drive assembly (143) and the tray lifting positioning rod (144), can realize the elastic movement of the slide preparation compartment tray (127) in the vertical direction; the bottom of the tray is equipped with a slide preparation compartment tray push motor to drive the lifting; the tray lifting positioning rod (144) and the tray push drive assembly (143) work together to assist the vertical guide tray in moving up and down.

[0033] The centrifugal slide preparation unit (Form 2) can also be implemented independently as a centrifugal sedimentation liquid-based cell slide preparation machine. Its usage process is as follows: Cell preservation solution is pre-filled into the centrifugal preservation solution bottle (124). After the doctor takes a sample, a sampling brush is placed inside the preservation solution bottle, the cap is tightened, and the preservation solution bottle is sent to the laboratory for processing. The cap is unscrewed and installed on the centrifugal turntable (121) via the lugs on both sides. The corresponding slide (103) is placed on the slide guide tray (102), placed into the slide preparation chamber (128), and locked securely with the slide preparation chamber tray hole and the latch (1271). The tray (127) is placed on the slide guide tray (102) and positioned, and the screw positioning pin (141) is tightened to fix it. After assembling the reagents and consumables, the machine is started, and the centrifugation gradient density separation liquid is automatically added to the preservation liquid bottle first. The centrifugation turntable motor (122) is started to drive the centrifugation turntable (121) to centrifuge the sample liquid for several minutes. The centrifugation turntable motor (122) is started to make the position of the preservation liquid bottle correspond to the waste liquid push rod (129) in sequence, and the push rod motor B (130) is started to push the mouth of the preservation liquid bottle to rotate outward and pour out the waste liquid in sequence into the waste liquid tank (106). In order to achieve better separation effect, this centrifugation program can be repeated several times. After completion, buffer solution is automatically added to the centrifugation preservation bottle (124); the centrifugation vibration motor (1212) is started for several minutes to break up the sample cells; the centrifugation turntable motor (122) is started to make the preservation bottle position correspond to the sample pusher (131) in sequence, and the pusher motor C (132) is started to push the mouth of the preservation bottle to rotate inward and pour out the sample solution in sequence into the corresponding slide preparation chamber (128); after standing for several minutes, the cells settle, adhere and fix on the glass slide (103); after settling, the flushing pump (203) and flushing pipeline system (112) are started to flush the glass slide (103) with buffer solution along the flushing channel (113), while at the same time the tray pusher drive component (143) is started to lift the slide preparation chamber tray (127) to separate the slide preparation chamber (128) and the glass slide (103). Centrifugation preparation is completed, followed by the transfer and staining procedure of the glass slide (103).

[0034] Example 3: Application of staining unit technology module and single-cylinder pathological staining machine The application of staining unit (2) and single-cylinder pathological staining machine combined Figure 4The structure and working principle are explained as follows: The staining tank (202) is equipped with several liquid level sensors (2021) at different heights on its wall to detect and control different liquid levels. It is used in conjunction with the buffer pump (203). The buffer pump (203) includes a buffer pump-buffered valve pipeline (2031) and a buffer pump inlet connector (2032). Various staining reagents are used by a two-way liquid pump (204) and a two-way liquid valve group (206) to alternately pump and release liquid to complete the staining process. The two are connected through the two-way liquid pump-liquid valve group pipeline (2041). Several external reagents are connected to the two-way liquid valve group (206) through the reagent connector (2071). The two-way liquid pump (204) is directly connected to the staining tank (202) through the two-way liquid pump-staining tank pipeline (2042) and is operated in conjunction with the buffer valve (205). After the same reagent is added for reaction, it can be pumped back to the liquid bottle for recycling. Multiple staining and cleaning are completed in a single tank. In addition, the bottom of the dyeing tank (202) is connected to a waste liquid discharge valve (220) or a liquid pump. The waste liquid and sediment are discharged through the dyeing tank discharge pipe (221) and the waste liquid discharge pipe (222), which can realize simultaneous rinsing and waste discharge, or emptying of waste dyeing liquid without recycling. At the same time, this application also provides a buffer valve-dyeing tank pipeline (208) and a buffer valve-rinsing system pipeline (209) to cooperate with the above operations.

[0035] The staining unit technology module can be used independently as a single-cylinder pathological staining machine for routine and special staining of cytopathological smears and tissue sections. The specific operation process is as follows: Place the slide holder (201) containing the prepared slides (103) into the staining cylinder (202); connect different external reagent bottles as needed, taking Papanicolaou staining as an example, they are: buffer solution, ethanol, hematoxylin, EAOG, etc.; after setting the automatic staining program and duration, start the staining machine: ethanol fixation, adding buffer solution to water, hematoxylin staining, buffer solution blueing, ethanol dehydration, EAOG staining, ethanol elution, and then take out the slides (103) for clearing (xylene or other) and mounting. Users can set whether to flush and discharge waste simultaneously, and whether to circulate or not recycle the staining solution.

[0036] Example 4: Application of connection component technology modules and their combinations Combination Figure 3 , Figure 4 , Figure 5A , Figure 5B , Figure 5CThe structure and principle of the connecting component technology module between the slide preparation unit (1) and the staining unit (2) are explained. A staining tank slide guide groove (213) is added to the upper edge of the staining tank (202) in Example 3; a slide frame lifting drive assembly (214) for controlling the lifting and lowering is added to the slide frame (201); a slide frame lifting beam (210) is set in the middle, a slide frame lifting beam hanging groove (211) is set at the top, and a slide frame horizontal lock (212) is set; the slide frame lifting beam (210) is hung in the slide frame lifting beam hanging groove (211), and the connection between the slide frame and the lifting beam (2101) is located above the center of gravity of the slide frame (201) and allows the slide frame (201) to rotate freely; initially, the slide frame (201) is secured by the slide frame horizontal lock (212) to keep it in a horizontal state, at which time the connection between the slide frame and the lifting beam (2101) and the center of gravity of the slide frame are in different vertical positions.

[0037] In Example 1 or 2, a pusher motor A (110) and a slide pusher (109) are added to the slide guide tray (102) of the slide preparation unit. After the slide preparation is completed, the slide tray motor (111) rotates sequentially to control the guide groove of the slide guide tray (102), the staining tank slide guide groove (213), and the slide holder slot (2011) to be precisely aligned in a straight line; the pusher motor A (110) is started sequentially to drive the slide pusher (109) to push the slide (103) to move smoothly along the guide groove into the first slide holder slot (2011); then the slide holder (201) is controlled by the slide holder lifting drive assembly (214) to descend one slot position; then the slide (103) is pushed into the next slide holder slot (2011) again. After loading is completed, the slide holder lifting drive assembly (214) continues to drive the slide holder (201) to descend to the bottom. At this time, the slide holder horizontal lock (212) hits the edge of the staining tank (202) and triggers it to be released. When the slide holder (201) rises again, it flips to a vertical state under the action of the center of gravity offset and the gravity of the slide holder (201) itself. Then it descends again into the staining tank (202) to prepare for staining.

[0038] Examples of combined implementation applications and operation procedures are as follows: Combination (1) Centrifuge-free cell slide preparation and staining machine: The centrifugation-free slide preparation unit (1) (Form 1) and the staining unit (2) are connected by a connecting member. After the slides are prepared, the slides are pushed horizontally to the slide holder one by one by an electric pusher; the slide holder is flipped to a vertical position; the subsequent steps are the same as those of a single-cylinder pathology staining machine.

[0039] Combination (2) Cell centrifugation, slide preparation, and staining integrated machine: The centrifugation slide preparation unit (1) (Form 2) and the staining unit (2) are connected by a connecting member. After the slides are prepared, the slides are pushed horizontally to the slide holder one by one by an electric pusher; the slide holder is flipped to a vertical position; the subsequent steps are the same as those of a single-cylinder pathology staining machine.

[0040] Combination (3) Cell preparation and staining assembly line: The slide preparation unit (1) is changed to a ring and rotates in a synchronous belt. It is connected to the staining unit (2) through the connecting component to realize a continuous and uninterrupted feeding and unloading assembly line device without gripping. Scanning and coding can also be added at the front end; and sealing, scanning, and AI automatic slide reading modules can be added at the back end to realize full-function and intelligent cell pathology detection.

Claims

1. A natural sedimentation type liquid-based cell preparation and single-cylinder pathological staining device, characterized in that, The system includes a slide preparation unit, a staining unit, and connecting components between the two. Sample solution is prepared in the slide preparation unit, and the connecting components transfer the prepared slides to the staining unit for further staining. The slide preparation unit employs a centrifugation-free preparation method, characterized in that the sample solution undergoes enrichment pretreatment in a capless preservation bottle without centrifugation. The sample solution is directionally and quantitatively transferred, naturally settled, and cells adhere to the slide by pushing open the drain valve, thus completing liquid-based cell preparation. The staining unit is an independently usable single-cylinder pathological slide staining device. The staining process is completed within a single staining cylinder by alternately drawing and releasing reagents. The connecting components between the slide preparation unit and the staining unit include: a slide pusher device to push the slides into the slide holder, a device to flip the slide holder from a horizontal to a vertical position, and a device to drive its lifting and lowering.

2. The natural sedimentation type liquid-based cell preparation and single-cylinder pathological staining device according to claim 1, characterized in that, The capless preservation solution bottle allows for the directional and quantitative transfer of sample solution to a predetermined position on a glass slide without opening the cap. Specifically, the bottle is equipped with a drain valve; at least one of the inlet and outlet of the drain valve is normally closed; the valve stem and valve disc of the drain valve are an elastic, integrated structure, with the valve disc's edge fixed and the valve stem movable in the middle; under a pushing force, the valve stem moves the inlet and outlet to the open state; when the pushing force is released, the valve stem and valve disc return to their original positions, and the drain valve returns to its normally closed state; the valve stem protrudes beyond the preservation solution bottle to form its pressure-bearing end, and its extension trajectory forms a weir, with the outlet located on its weir wall; during draining, the glass slide pushes and presses against the pressure-bearing end at a predetermined position, forming a fixed-volume sealed space together with the weir.

3. The natural sedimentation type liquid-based cell preparation and single-cylinder pathological staining device according to claim 1, characterized in that, The aforementioned capless preservation bottle pre-treats the sample solution and enriches abnormal cells before discharge, replacing the centrifugation pre-treatment method. Specifically, it includes: pre-filling with a modified cell preservation solution; pre-placing with materials for adsorbing and filtering impurities; and mechanically vibrating the preservation bottle during slide preparation to detach and transfer more and heavier abnormal cells.

4. A natural sedimentation type liquid-based cell slide preparation and single-cylinder pathological staining device according to any one of claims 1 or 2, characterized in that, The centrifugation-free slide preparation unit includes a preservation liquid bottle tray with a slide guide tray below it, both of which can rotate under motor drive. Several capless preservation liquid bottles are fixedly positioned on the preservation liquid bottle tray, with their drain valve stems and pressure-bearing ends facing downwards. Several glass slides are placed on the slide guide tray, corresponding one-to-one with the positions of the capless preservation liquid bottles above. When a preservation liquid bottle is pressed downwards, the valve stem is pushed by the glass slide to the drain valve open state, transferring the sample liquid to the designated position on the glass slide. Conversely, when the capless preservation liquid bottle and its valve stem are lifted away from the pressed glass slide, the drain valve returns to its normally closed state. A vibration motor capable of actuating the centrifugation-free preservation liquid bottles is installed on the slide preparation unit.

5. The natural sedimentation type liquid-based cell preparation and single-cylinder pathological staining device according to claim 1, characterized in that, In addition to the centrifugation-free form, the slide preparation unit also includes a centrifugation form, characterized in that the centrifugation form includes a centrifugal preservation bottle for centrifuging and pouring the sample solution, and a centrifugal turntable for fixing and centrifugal movement; a fixed liquid path and a liquid inlet are provided above the preservation bottle; a slide preparation chamber and its slide preparation chamber tray are provided at corresponding positions below the centrifugal preservation bottle and the centrifugal turntable; a glass slide and its slide guide tray, consistent with claim 4, are fixedly located below the slide preparation chamber and its slide preparation chamber tray.

6. The natural sedimentation type liquid-based cell preparation and single-cylinder pathological staining device according to claim 5, characterized in that, The centrifugal slide preparation unit has a preservation solution bottle with a hanging loop, and the centrifugal turntable has a storage slot for the preservation solution bottle. The centrifugal motor is installed above the centrifugal turntable and also serves as the turntable positioning motor. The opened centrifugal preservation solution bottle is installed on the storage solution bottle storage slot through the preservation solution bottle hanging loop and is swung outward when the centrifugal turntable rotates. The slide preparation tray can drive all slide preparation chambers to move up and down. During slide preparation, the slide preparation chambers are pressed down to press the slides tightly, and conversely, after slide preparation is completed, all slide preparation chambers are lifted away from the slides. Several waste liquid dispensing pushers and sample dispensing pushers are respectively set on the top and bottom sides of the centrifugal preservation solution bottle. The waste liquid dispensing pushers push the mouth of the centrifugal preservation solution bottle to rotate to one side, and the waste liquid is poured into the waste liquid tank. The vibration motor linked to the preservation solution bottle can break up the sample cells. Starting the turntable motor allows the preservation solution bottle to be positioned sequentially to the corresponding inverted sample pusher; the inverted sample pusher pushes the mouth of the centrifuged preservation solution bottle to rotate to the other side, and the sample solution is poured into the corresponding slide preparation chamber below.

7. The natural sedimentation type liquid-based cell slide preparation and single-cylinder pathological staining device according to claim 1, characterized in that, The staining unit can be used independently for staining pathological sections without relying on other components of the present invention. The staining unit includes a single staining cylinder, a slide holder, and a liquid system. Staining is completed by alternating pumping and releasing of liquid in the single staining cylinder, as follows: one end of the staining cylinder is connected to a bidirectional liquid pump, and the other end is connected to a bidirectional liquid valve group, and then connected to the corresponding reagent bottles through multiple pipes; the staining cylinder is equipped with several liquid level sensors to control the liquid level to a set height; the inlet and outlet of the liquid bottle are in the middle of the liquid bottle, and a waste liquid discharge switch is set at the bottom.

8. The natural sedimentation type liquid-based cell preparation and single-cylinder pathological staining device according to claim 1, characterized in that, The connecting component connects the slide preparation unit and the staining unit, specifically including: a slide pusher component, a slide holder lifting and flipping component; when transferring slides, the slide guide tray rotates and positions itself, and the slide holder is lifted and positioned, so that the guide groove of the slide guide tray, the slide guide groove of the staining cylinder, and the slide holder slot are aligned into a straight line. The slide pusher is activated to push the slide into the slide holder slot along the two guide grooves until it reaches its end; before the flipping component is triggered, there is a horizontal positional difference between the center of gravity of the slide holder and the rotatable lifting beam connection point. After the vertical flipping component is triggered, the slide holder's own weight is used to restore the two to a vertically aligned position.

9. The natural sedimentation liquid-based cell preparation and single-cylinder pathological staining device according to claim 4, wherein the slide preparation unit is characterized in that the slide guide tray is provided with a flushing channel, and a flushing pipeline system and its outlet are provided upstream of the slide. The system is opened at regular intervals so that the flushing system can flush away cells and impurities outside the set range and those that are not adhered to the slide.

10. A natural sedimentation type liquid-based cell preparation and single-cylinder pathological staining device according to claim 2, characterized in that, The slides used have sufficient adhesion to the cells; the cell preservation solution used must be compatible with the slides to ensure that the preservation solution does not impair the adhesion of the slides; the cell preservation solution used in the centrifugation-free slide preparation method is sufficient to dissolve impurities such as red blood cells and protein mucus.

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