Full-automatic dyeing system and dyeing process
By introducing a large-capacity reagent warehouse, a transfer waiting area and an automatic reagent replacement mechanism into the fully automatic staining system, the problem of the existing system's inability to meet the high daily throughput and frequent reagent replacement is solved, and unattended high-throughput samples are achieved. deal with.
Patent Information
- Application Number
- CN202411608567.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-11-12
- Publication Date
- 2025-01-24
AI Technical Summary
The existing automatic staining system cannot meet the daily processing needs of hospital pathology departments, research institutes or laboratories, and needs to frequently replace and supplement small reagents during the staining process, resulting in high-throughput processing obstacles and unattended difficulties.
A fully automatic dyeing system is designed, including a reagent warehouse with large capacity and high stability, a transfer waiting area and a refrigeration mechanism. It can store hundreds of small reagents and automatically replace reagents through a second transfer mechanism to achieve unattended operation. high-throughput processing.
It achieves high-throughput sample processing, can work continuously without any supervision, reduces the intervention of human factors, improves sample stability and consistency, and meets the needs of high daily processing volume.
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Figure CN119354660A_ABST
Abstract
Description
Technical Field
[0001] The invention relates to a full-automatic staining system, in particular to a full-automatic staining system and a staining process for processing biological samples. Background Art
[0002] Biological samples need to be processed and tested for purposes such as medical diagnosis or experimental research. The processing of biological samples is usually a long process, including collecting samples, processing samples, preparing microscope slides, staining, examining, retesting or re-staining; collecting additional samples, re-examining samples, and finally providing a diagnosis.
[0003] At present, there are automatic staining systems for biological sample processing, which can realize the processing of human or animal samples for histology or pathology. However, the existing automatic staining systems have many defects. For example, the daily processing capacity of the fully automatic staining system instruments in the relevant field is small, which cannot meet the daily processing capacity requirements of hospital pathology departments, various scientific research institutes or laboratories.
[0004] In addition, due to the wide variety of reagents needed in the staining process, early staining systems mostly used batch processing of samples based on sample index classification (for example, samples that required the same type of reagents were processed in the same batch), so fewer types of antibody reagents were required, which also reduced the frequency of antibody reagent replacement.
[0005] However, with the development of precision diagnosis and treatment, at present, more and more clinical cases need to be put on the machine according to the patient's case. Generally speaking, the slice index of a patient generally requires 8-10 slices, or even higher. In addition, the types of reagents required for the analysis and processing of samples are different, and the diagnosis link requires the simultaneous presentation of all the index stains of the case. At the same time, the types of indicators for precision diagnosis and treatment have continued to grow in recent years, and the types and numbers of proteins and nucleic acids required for corresponding research, testing or diagnosis have also continued to increase. Similarly, the number of targets and genes of concern is also increasing. Therefore, during the operation of domestic and foreign competitive instruments on the market, they are alarmed to frequently replace and supplement the required small reagents, which has become an obstacle to high-throughput processing. And in this process of constantly replenishing reagents or samples, it is required to arrange manual duty. This makes continuous work at night more difficult or brings a greater workload to the staff. Summary of the invention
[0006] In order to overcome the above-mentioned shortcomings, the purpose of the present invention is to provide a fully automatic staining system that can increase the number of samples processed per day and meet the daily processing volume requirements of hospital pathology departments, various scientific research institutes or experimental research.
[0007] In order to achieve the above purpose, the technical solution adopted by the present invention is: a fully automatic dyeing system, including a processing chamber, an incubation area is arranged in the processing chamber, the incubation area is provided with a plurality of incubation positions, the number of the incubation positions is n, and further comprising: A transfer waiting area, which is arranged in the processing chamber and is used to place slides to be processed and slides to be sent out after processing. Before the fully automatic staining system starts working, the number of slides located in the transfer waiting area is N, and N / n≥1. The slides to be processed refer to slides that have been attached to the slides but have not been pre-treated such as immersion staining. A reagent warehouse is arranged in the processing chamber, a refrigeration mechanism is arranged in the reagent warehouse, and the reagent warehouse can accommodate several kinds of small reagents.
[0008] The dyeing system of the present invention has the following beneficial effects: ① The types or quantities of small reagents in the reagent bin of the present application can reach hundreds, even hundreds or thousands. This is significantly different from the prior art, which has only dozens of small reagents. In addition, in order to solve the high-throughput and unattended problems raised in the background technology, the present application not only greatly increases the number and types of small reagents, but also cooperates with the setting of the transfer waiting area, so that a sufficient number of samples can be accommodated in the processing chamber. Therefore, on the basis of ensuring the use requirements of various reagent varieties and quantities, with sufficient samples and sample placement areas, truly unattended is achieved, and high-throughput processing effects are fully realized.
[0009] ② Since the present application is provided with a reagent warehouse with large storage capacity and high stability, as well as a transfer waiting area, the entire staining system is in a closed state (i.e., there is no need to open the door of the reagent warehouse or the door or shell of the loading area) during a long experimental process. Therefore, it reduces the accidental touch caused by the semi-open setting of the staining system in the prior art; and effectively reduces the intervention and influence of human factors in the entire process of staining, so that the accuracy and credibility of the production result data are higher, which is crucial for medical devices and scientific instruments.
[0010] ③ The present application can ensure the stability of the biochemical titers of dozens or even hundreds of small reagents in the reagent warehouse by setting a refrigeration mechanism in the reagent warehouse. Since the staining system of the present application can achieve the effect of unattended operation and even non-stop operation at night, the staining system of the present application can process up to 100-600 or even higher number of slides in a cycle of work. Therefore, the titer stability of small reagents is crucial to the consistency of the sample processing effect of the present application. Therefore, by setting a refrigeration mechanism in the reagent warehouse of the present application, and cooperating with the large-capacity reagent warehouse and the transfer waiting area, the high throughput of the staining system of the present application and the sufficiently high sample stability and consistency in the unattended process are achieved.
[0011] Furthermore, the transfer waiting area is provided with a waiting fixed slot, and the waiting fixed slot can fix the glass slide to be processed; there are multiple waiting fixed slots, and each waiting fixed slot can accommodate at least one slide rack with a glass slide. By setting multiple waiting fixed slots, the ratio of N / n is improved. The more waiting fixed slots there are, the greater the ratio of N / n, so that the unattended time that the glass slide can support is longer, and the round of slide production is higher.
[0012] Furthermore, the reagent compartment is provided with a second transfer mechanism and a small reagent transfer mechanism, and the second transfer mechanism can transfer the small reagent to the small reagent transfer mechanism, waiting for the sampling mechanism to take samples. When a small reagent is needed, the second transfer mechanism provided in the reagent compartment automatically transfers the small reagent to the small reagent transfer area, eliminating the need for staff to frequently replace small reagents, thereby extending the time that staff can leave the machine, and allowing the staining system to process samples uninterruptedly without supervision.
[0013] Further, the small reagent transfer mechanism includes a transfer support plate, which forms a transfer cavity connected to the inside of the reagent compartment. The small reagent can be accommodated in the transfer cavity under the action of the second transfer mechanism. The transfer support plate is provided with a plurality of sampling through holes, and the sampling mechanism can pass through the sampling through holes for sampling. Through the setting of multiple sampling through holes, when a reagent bottle under one of the sampling through holes is being sampled, the reagent management system issues instructions to the second transfer mechanism, so that the second transfer mechanism transfers the second reagent bottle to be sampled next to the transfer cavity in advance to wait for sampling. After the reagent needle completes a sampling, it does not need to wait for the second reagent bottle to be transferred from the reagent rack to the small reagent transfer mechanism. The reagent needle can continuously sample the reagent in the second reagent bottle, saving the time of the second transfer mechanism to transfer the reagent bottle, improving the efficiency of the reagent needle sampling in the incubation stage, improving the incubation efficiency of the staining system, shortening the processing time of a single glass slide, and improving the efficiency of the staining system in processing glass slides.
[0014] Furthermore, the second transfer mechanism includes a second linear module, the second linear module is connected to the heat preservation shell of the reagent compartment, and also includes a second clamp connected to the second linear module, the second linear module can drive the second clamp to move in the X-axis, Y-axis and Z-axis directions, and the second clamp can clamp a small reagent bottle. Through the arrangement of the second linear module and the second clamp, the second transfer mechanism can transfer the small reagent bottle in the X-axis, Y-axis and Z-axis directions.
[0015] Further, the second transfer mechanism also includes a second driving member, the second driving member is connected to the second clamping claw, the second driving member can drive the second clamping claw to clamp the small reagent bottle, and then transfer the position of the small reagent bottle through the second linear module; the second transfer mechanism also includes a second motor, the second motor is connected to the second linear module, the output shaft of the second motor is connected to the second driving member, and the second motor can drive the second clamping claw to rotate by driving the second driving member to rotate. Through the setting of the second motor, the direction in the second clamping claw can be adjusted according to the position of the small reagent bottle to ensure that the second clamping claw can accurately grasp the small reagent bottle.
[0016] Furthermore, the reagent compartment is provided with a reagent inlet and outlet, a reagent rack is provided in the reagent compartment, the reagent rack can accommodate hundreds of small reagents, and the second transfer mechanism can transfer the reagents located at the reagent inlet and outlet and the small reagent bottles located on the reagent rack. When the small reagent is used up, the small reagent bottle is transferred to the reagent inlet and outlet by the second transfer mechanism, and the staff takes out the small reagent bottle from the reagent inlet and outlet; the staff places the replacement small reagent bottle at the reagent inlet and outlet, and transfers the small reagent bottle to the reagent rack by the second transfer mechanism, thereby completing the replacement or replenishment of the small reagent.
[0017] Furthermore, a second code scanning component is provided in the reagent compartment, the second code scanning component is connected to the second transfer mechanism, and the second code scanning component can scan the information on the small reagent bottle and enter it into the reagent management system. Through the setting of the second code scanning component, before the second driving member grabs the small reagent bottle, the second code scanning component scans the information on the small reagent bottle and enters it into the reagent management system, and then transfers the small reagent to the corresponding position of the reagent rack through the second transfer mechanism.
[0018] Furthermore, a sample loading area, a staining area, an incubation area, and a sealing area are provided in the processing chamber, and the slides can be transferred between different areas through a first transfer mechanism, and different stages of processing can be performed in different areas. By respectively providing the sample loading area, the staining area, the incubation area, and the sealing area in different spaces in the processing chamber, the sample tissue is processed at different stages in different areas, so that the sample tissue is processed in an assembly line mode, the number of slides that can be accommodated by the staining system at the same time can be increased, and the efficiency of the staining system in processing slides can also be improved.
[0019] Furthermore, a sample loading mechanism is provided in the sample loading area, and the sample loading mechanism includes a sample loading fixing groove, and the sample loading fixing groove can accommodate a slide rack with a glass slide. During the sample loading process, the technician simply places the slide rack with the glass slide in the sample loading fixing groove, which is convenient for operation.
[0020] Furthermore, the loading mechanism includes a lifting component and a first code scanning component, wherein the lifting component can drive the glass slide to move upward, and the first code scanning component can scan the glass slide driven by the lifting component. Through the cooperation between the lifting component and the first code scanning component, it is ensured that the QR code of each lifted glass slide can be clearly scanned.
[0021] Furthermore, a driving component is included, and the driving component can drive the lifting component and the first code scanning component to move synchronously. Through the setting of the driving component, the position between the lifting component and the first code scanning component is relatively fixed, ensuring that the distance between the first code scanning component and each lifted glass slide is the same.
[0022] Furthermore, the lifting assembly includes a lifting cylinder fixedly connected to the driving assembly, and a lifting piece is provided on the telescopic rod of the lifting cylinder. The lifting cylinder can drive the lifting piece to move up and down, and a limiting groove is provided at one end of the lifting piece close to the sample fixing groove. In the process of lifting the glass slide by the lifting assembly, a partial area of the lifted glass slide is accommodated in the limiting groove.
[0023] Furthermore, a drying and dipping mechanism is provided in the dipping area, and the drying and dipping mechanism includes a drying and dipping tank, and the glass slides on the slide rack are transferred as a whole to the drying and dipping tank through the first transfer mechanism, and can be accommodated as a whole in the drying and dipping tank for baking or soaking.
[0024] Furthermore, the sealing area is provided with a sealing mechanism, which is used to seal the incubated sample tissue. Through the setting of the sealing mechanism, the sealing of the slide can be completed in the staining system, and the technicians do not need to do post-processing of the sealing outside the staining system, which saves the technicians' post-processing workload, and at the same time saves the cost of purchasing the sealing machine in the laboratory and saves the floor space occupied by the sealing machine.
[0025] Furthermore, the slide rack includes two fixing plates arranged at the ends, and stopper protrusions are arranged on the outer sides of the two fixing plates, and the stopper protrusions are arranged close to the upper ends of the fixing plates. By setting the stopper protrusions, the first transfer mechanism prevents the slide rack from falling off the first transfer mechanism during the process of clamping the slide rack, thereby increasing the safety during the slide transfer process.
[0026] Furthermore, the first transfer mechanism includes a first linear module and a first clamp connected to the first linear module, and the first linear module is a three-axis linear module that can drive the first clamp to move in the X-axis, Y-axis and Z-axis directions.
[0027] Furthermore, the first transfer mechanism also includes a clamping rotation assembly connecting the first linear module and the first clamping jaw, and the clamping rotation assembly can drive the first clamping jaw to clamp the slide rack, and can rotate the slide rack to change the angle of the slide rack.
[0028] Furthermore, the clamping rotation assembly includes a first motor and a first gear, the output shaft of the first motor is connected to the first gear, the first motor can drive the first gear to rotate, the first clamp includes two symmetrically arranged clamp members, the clamp member includes a clamping portion for clamping the slide rack, and a connecting portion connected to the first gear, a linearly arranged sawtooth is provided on one side of the connecting portion close to the first gear, the saw teeth respectively connected to the two clamp members are located on opposite sides of the first gear, and are respectively meshed with the first gear, and during the rotation of the first gear, the two clamp members can be driven to approach or move away from each other through the saw teeth.
[0029] Furthermore, the clamping rotating assembly also includes a guide member, which is provided with two parallel guide grooves, and the connecting part is arranged in the guide grooves. During the process of the connecting part moving toward each other under the action of the first gear, the connecting part moves along the guide groove in the guide groove; the guide member is provided with an avoidance groove, the position of the avoidance groove is adapted to the position of the first gear, the avoidance groove and the guide groove are connected, the first gear is accommodated in the avoidance groove, and can drive the first clamping jaw to clamp the slide rack through the saw teeth.
[0030] By setting up the clamping and rotating assembly, both the action of clamping the slide rack and the action of adjusting the angle of the slide rack can be completed. One assembly completes multiple functions, reducing the parts of the first transfer mechanism and making the structure of the first transfer mechanism simpler.
[0031] Furthermore, the bottom layer of the processing chamber is provided with a waste liquid area and a large-capacity reagent area, a first working area is provided above the large-capacity reagent area, the first working area is provided with at least one of a loading area, a transfer waiting area, a drying and dyeing area, and a sealing area, a second working area is provided above the first working area, and at least an incubation area is provided in the second working area. By arranging the first working area and the second working area in layers in height, the floor space occupied by the dyeing system is reduced, and the floor efficiency ratio of the dyeing system is improved.
[0032] A dyeing process, based on the fully automatic dyeing system as described in any one of the above items, the dyeing process comprises the following steps being performed continuously and uninterruptedly: S1: In the first working area, a slide rack carrying a slide is loaded onto a loading mechanism; S2: Directly transfer the slide rack to the transfer waiting area to wait for processing; S3: placing the first slide rack carrying the slides into the drying and staining mechanism, and performing batch baking and antigen repair on the slides; S4: transporting the first slide rack to a second working area, wherein the second working area is at a different height from the first working area; S5: sending the glass slides on the first glass slide rack to the incubation mechanism for incubation in sequence, and placing the second glass slide rack carrying the glass slides into the drying and staining mechanism; S6: Recover the glass slides on the first glass slide rack from the incubation mechanism to the first glass slide rack and then transport them back to the first working area, transport the second glass slide rack carrying the glass slides to the second working area for incubation; place the third glass slide rack carrying the glass slides into the drying and staining mechanism; S7: After sealing the first slide rack carrying the slides in the first working area, the first slide rack is transported to the transfer waiting area; the slides on the second slide rack are recovered to the second slide rack and then transported back to the first working area for sealing; the third slide rack carrying the slides is transported to the second working area for incubation, and the fourth slide rack carrying the slides is transported from the transfer waiting area to the drying and staining mechanism, thereby continuously repeating the above steps S3-S6.
[0033] The dyeing system of the present invention has the following beneficial effects: 1) Through the setting of the transfer waiting area, the staining system can complete the loading of hundreds or even several hundred slides at a time. After the slides are loaded, the staining system can perform continuous and uninterrupted processing on its own. Even if the staff is away from the machine for a long time, it will not affect the processing efficiency of the staining system. Therefore, the staining system can continue to work during the day at night, making full use of the night time. 2) Through the setting of the reagent warehouse, the reagent warehouse has a low-temperature storage function and can store hundreds or even thousands of small reagents to meet the types of small reagents required for daily processing. There is no need for staff to frequently change the types of small reagents, which prolongs the time when the staff is away from the machine, and it is not easy to stop the machine due to insufficient reagent types.
[0034] 3) By setting up a transfer waiting area and reagent warehouse, the staff's time away from the machine is extended, and samples can continue to be processed unattended at night, increasing the number of samples processed per day, thus achieving a high-throughput effect.
[0035] 4) The loading module directly uses a slide rack for loading, and uses the slide rack to drive the slides to move in various areas, which improves the transfer efficiency and has flexibility. There is no need to transfer the slides to a dedicated transport carrier for the staining system, nor is there a need to configure a dedicated transport carrier for the staining system, which effectively improves space utilization and floor efficiency.
[0036] 5) By arranging the sample loading area, the staining area, the incubation area and the sealing area in different spaces in the processing chamber, the sample tissue is processed at different stages in different areas, so that the sample tissue is processed in an assembly line mode, which can increase the number of slides that the staining system can accommodate at the same time and improve the efficiency of the staining system in processing slides.
[0037] 7) Through the setting of the sealing mechanism, the sealing of the slides can be completed in the staining system, and the technicians do not need to do post-processing of the sealing outside the staining system, which saves the technicians' post-processing workload, and at the same time saves the laboratory the cost of purchasing the sealing machine and the floor space occupied by the sealing machine.
[0038] 8) The staining system of the present invention can support the function of freely loading samples according to cases, so as to meet the diverse and complex clinical testing requirements to a greater extent, without having to perform separate tests according to the types of small reagents, and truly realizes the random loading of the staining system, breaking the limitations of clinical use. It is also friendly to the staff, and there is no need to frequently load materials or perform night duty. BRIEF DESCRIPTION OF THE DRAWINGS
[0039] The drawings constituting a part of this application are used to provide a further understanding of the present invention. The illustrative embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute improper limitations on the present invention.
[0040] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the following briefly introduces the drawings required for use in the description of the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.
[0041] Figure 1 A three-dimensional diagram of a dyeing system according to an embodiment of the present invention; Figure 2 A three-dimensional diagram of a dyeing system without a shell according to an embodiment of the present invention; Figure 3 This is a schematic diagram of the connections of various mechanisms in the first working area of an embodiment of the present invention; Figure 4 A three-dimensional diagram of a sample loading mechanism according to an embodiment of the present invention; Figure 5A three-dimensional diagram of a sample loading mechanism from another perspective of an embodiment of the present invention; Figure 6 for Figure 5 A partial enlarged view of Figure 7 A three-dimensional diagram of a transfer waiting area according to an embodiment of the present invention; Figure 8 A three-dimensional diagram of a drying and dyeing mechanism according to an embodiment of the present invention; Figure 9a A three-dimensional diagram of a film sealing mechanism according to an embodiment of the present invention; Figure 9b A three-dimensional diagram of a film sealing mechanism from another perspective of an embodiment of the present invention; Fig.10 is a three-dimensional diagram of a first transfer mechanism according to an embodiment of the present invention; Fig.11 for Fig.10 A partial enlarged view of Fig.12 A three-dimensional diagram of a first transfer mechanism without a guide member according to an embodiment of the present invention; Fig.13 for Fig.12 A partial enlarged view of Fig.14 A three-dimensional diagram of a guide member according to an embodiment of the present invention; Fig.15 A three-dimensional diagram of a guide member of an embodiment of the present invention from another perspective; Fig.16 is a three-dimensional diagram of a slide holder according to an embodiment of the present invention; Fig.17 A three-dimensional diagram of a reagent compartment according to an embodiment of the present invention; Fig.18 A three-dimensional diagram of a reagent compartment without a heat-insulating layer according to an embodiment of the present invention; Fig.19 Another stereoscopic view of a reagent compartment without a heat-insulating layer according to an embodiment of the present invention; Fig. 20 It is a three-dimensional diagram of a second transfer mechanism according to an embodiment of the present invention.
[0042] In the figure: 1. Sample loading mechanism; 11. Sample loading workbench; 12. Sample loading fixing groove; 13. Sample loading bracket; 14. Driving assembly; 141. Sample loading driving motor; 142. Slide rail; 143. Sliding block; 144. Lifting and scanning support plate; 15. Lifting assembly; 151. Lifting cylinder; 152. Lifting part; 153. Limiting groove; 16. First scanning assembly; 2. Transit waiting area; 21. Waiting for fixed slot; 3. Drying and dyeing mechanism; 31. Drying and dyeing tank; 32. Dipping cover; 33. Driving cylinder; 34. Liquid inlet and outlet channels; 4. Sealing mechanism; 41. Lifting assembly; 42. Ejecting assembly; 43. Sealing assembly; 44. Adsorption assembly; 45. Tank body; 5. first transfer mechanism; 51. first linear module; 52. clamping and rotating assembly; 521. first motor; 522. first gear; 523. guide member; 5231. guide groove; 5232. avoidance groove; 53. first clamping claw; 531. clamping part; 532. connecting part; 533. sawtooth; 6. slide holder; 61. fixing plate; 62. fixing rod; 63. spacer block; 64. stopper protrusion; 65. slide; 7. Reagent bin; 71. Insulated shell; 72. Reagent inlet and outlet; 73. Small reagent transfer mechanism; 731. Transfer lower support plate; 732. Transfer upper support plate; 7321. Sampling through hole; 733. Connecting plate; 734. Transfer cavity; 74. Reagent rack; 75. Second transfer mechanism; 751. Second linear module; 752. Second motor; 753. Second driving member; 754. Second clamp; 76. Second code scanning component; 77. Small reagent bottle; 78. Refrigeration mechanism; 8. Support frame; 81. Elevator; 9. Shell; 100, large-capacity reagent area; 200, waste liquid area; 300, first working area; 400, second working area; 500, small reagent area. DETAILED DESCRIPTION
[0043] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the specific embodiments of the present invention are described in detail below in conjunction with the accompanying drawings. In the following description, many specific details are set forth to facilitate a full understanding of the present invention. However, the present invention can be implemented in many other ways different from those described herein, and those skilled in the art can make similar improvements without violating the connotation of the present invention, so the present invention is not limited by the specific embodiments disclosed below.
[0044] In addition, the term "and / or" in this article is only a description of the association relationship of associated objects, indicating that there can be three relationships. For example, A and / or B can represent: A exists alone, A and B exist at the same time, and B exists alone. In addition, the character " / " in this article, unless otherwise specified, generally means that the associated objects before and after are in an "or" relationship.
[0045] Explanation of terms: The "small reagents" of this application include but are not limited to: antibodies, samples, nucleic acids, dyes, ligands, ligand receptors, enzymes or enzyme substrates, conjugates (for example, biotin, avidin, streptavidin, etc.), metals (such as silver or gold particles) and metal enhancers, signal molecules or any other molecules suitable for the desired application, as well as various other auxiliary reagents, etc.
[0046] The "bulk reagents" in this application include, but are not limited to: reagents required for sample processing and staining or reagents used for dissolution, cleaning and detection, such as distilled water, cleaning solution, buffer solution, repair solution, dewaxing solution, alcohol, etc.
[0047] The fully automatic staining system of the present application can be applied to the positioning, qualitative and quantitative tests, research or diagnosis of various biological samples. The fully automatic staining system of the present application can be used to provide biological sample processing and detection for pathological diagnosis, and is suitable for a variety of staining methods for pathological specimens, including but not limited to immunohistochemistry IHC, ICC, in situ hybridization ISH, RNAscope, fluorescence in situ hybridization FISH, multiple staining mIHC, conventional drip staining HE, special staining and various rapid freezing staining, etc.
[0048] See attached Figure 1-3 As shown, the fully automatic staining system of the present application includes a support frame 8 and a shell 9, and the shell is fixed by the support frame. A processing cavity is formed inside the shell. The fully automatic staining system of the present application includes a reagent bin with a cooling function and multiple storage positions, so that it can ensure that the system has an adequate supply of reagents during uninterrupted operation, without the need for manual replenishment of reagents; at the same time, in conjunction with the transit waiting area of the system, by temporarily storing a large number of slides to be processed in the transit waiting area, a large number of samples that may be needed during long-term uninterrupted film making and staining work can be prepared, and there is no need for frequent manual loading of samples. As a result, the system of the present invention can achieve uninterrupted operation for a long time without manual intervention, thereby achieving the unattended effect of the entire system, especially for nighttime operation, and can also achieve the effect of the same system not stopping day and night, thereby achieving a high-throughput processing effect.
[0049] Regarding the relationship between the number of samples in the transfer waiting area and the number of incubation positions, currently, most of them are done by placing the same number of slides as the incubation positions, or slightly more than the number of incubation positions, into the processing chamber. Therefore, after one batch of slides is processed, it is necessary to manually load the second batch of slides. In some embodiments of the present invention, the number of incubation positions in the processing chamber is n, and the number of slides located in the transfer waiting area before the automatic staining system starts working is N, N / n ≥ 1, for example, n is 30, N is 360; or n is 40, N is 100; or n is 20, N is 200.
[0050] In some embodiments, N / n ≥ 2, or 3, or 4, or 5, or other ratios. Of course, N / n can also be a decimal ratio. Obviously, the larger the ratio of N / n, the longer the unattended time that the slide can support, and the higher the number of slide production rounds.
[0051] Different from the prior art, the present application sets a special transfer waiting area in the processing chamber. Please note that it is not a glass slide rack in the prior art, but an area for carrying the glass slide rack. The present application has a larger space for setting the transfer waiting area, and it is necessary to set such an area separately in the processing chamber, thereby providing sufficient space and position for the temporary storage of subsequent glass slides in the processing chamber. It also provides a basis for supporting the unattended effect of the whole machine of the present invention.
[0052] In some embodiments, when the fully automatic staining system of the present application is in working state, the shell fully encloses the processing chamber to form a closed processing chamber. The present invention is based on the setting of multi-position reagent warehouse and transfer waiting area, so that it can achieve that the shell does not need to be opened during the operation of the system, and the safety hazards caused by intentional or unintentional intervention of human body parts during the operation of the machine (such as accidental touch when laboratory technicians are working) can be effectively prevented. And due to the fully enclosed setting, the intentional or unintentional human factors in the whole process of making stains can be effectively avoided. Intervention and influence, thereby minimizing the impact of the external environment on the sample processing process, thereby improving the safety, effectiveness and objective credibility required by the quality of medical scientific instruments. It should be noted that the present application is different from the prior art in that, in ensuring a long-term (for example, it can be ≥4 hours, specifically, it can be 24 hours, 12 hours, 6 hours, etc.) continuous and uninterrupted film making process, there is no need to open the shell or need to add any reagents or slides in the middle. In the existing staining systems, although there have been reports that continuous operation can be achieved, most of them require opening the shell or cover in the middle of the experiment to replenish reagents or slides, which requires personnel to operate, especially at night, and it is difficult to do it unmanned.
[0053] See attached Figure 3 and attached Figure 7 As shown, in some embodiments, a waiting area is provided in the processing chamber, and a transfer waiting area 2 is provided in the waiting area. The transfer waiting area 2 includes a waiting support plate, and a waiting fixing groove 21 is provided on the waiting support plate. The waiting fixing groove 21 is used to fix the slide rack 6 holding the glass slide 65, and the slide rack 6 can accommodate multiple glass slides 65.
[0054] In some embodiments, the waiting fixed slots 21 are provided with a plurality of slide racks 6, and a plurality of slide racks 6 can be placed at the same time. After the slide 65 is loaded by the loading mechanism 1, when there are slides 65 being processed in the drying and dyeing area, the first transfer mechanism 5 transfers the loaded slide 65 together with the slide rack 6 and places them in the waiting fixed slot 21, so that the slide 65 is in a queue processing state, and the loading mechanism 1 can load other slides 65, thereby increasing the number of slides 65 information entered at one time, and increasing the number of slides 65 that can be accommodated by the staining system at the same time. After the information of the slide 65 is entered, the staining system can perform continuous and uninterrupted processing by itself, without the need for staff to load samples continuously, which can reduce the workload of staff, extend the time when staff are off the machine, and reduce the burden of labor.
[0055] In some embodiments, the waiting fixed slots 21 can be set to 2, 4, 6, 8, 10, 12 or other numbers. Taking the setting of 10 waiting fixed slots 21 as an example, 10 slide racks 6 can be placed in the waiting area at the same time, together with the 2 sample loading fixed slots 12 of the sample loading mechanism 1 itself, 12 slide racks 6 can be accommodated, and the staining system can complete the loading of 12 slide racks 6 and 360 slides 65 (taking 30 slides 65 that can be accommodated in each slide rack 6 as an example) at a time. After completing the loading of 360 slides, the staining system can perform continuous and uninterrupted processing by itself, and even if the staff is away from the machine for a long time, it will not affect the processing efficiency of the staining system.
[0056] The staining system can complete the processing of 180 slides within a standard day's working period (such as 9:00-17:00). Before the staff finishes the daytime sample processing (such as 17:00 or other time), the information of the glass slides 65 can be entered in batches, so there is no need for staff to be on duty. At night, the staining system will also perform continuous and uninterrupted processing based on the input information, which can increase the daily throughput to more than 500 slides. Compared with the prior art, the daily throughput of the staining system is 90 to 180 slides. This application increases the processing rate through zoning processing, and increases the daily throughput to more than 500 slides by setting up a waiting area and extending the processing time, which greatly increases the daily processing volume of 65 slides and reduces the sample processing pressure of the hospital.
[0057] See attached Figure 17-20 As shown, in some embodiments, a reagent bin 7 is also included, and the reagent bin 7 is used to load small reagents used for incubation. Since there are many types of small reagents used for incubation, the commonly used method is to store the small reagents in a refrigerator. Before the dyeing system works, the staff will place the small reagents needed in the dyeing system for incubation, and the staff cannot leave the machine for a long time. The present application sets a small reagent bin 7 in the dyeing system, and the reagent bin 7 can accommodate hundreds of small reagents to meet the demand for small reagent types in normal incubation.
[0058] In some embodiments, the reagent bin 7 includes an insulation shell 71, which forms a storage space. A refrigeration mechanism 78 is provided in the storage space to cool the storage space in the reagent bin 7, and the temperature in the reagent bin 7 is reduced to 4°C, which is suitable for long-term storage of small reagents, so that the small reagents can be stored in the reagent bin 7. When a small reagent is needed, the second transfer mechanism 75 provided in the reagent bin 7 automatically transfers the small reagent to the small reagent transfer area, so that the staff does not need to frequently replace the small reagents, thereby extending the time when the staff is off the machine, so that the staining system can work uninterruptedly without being supervised.
[0059] In some embodiments, the second transfer mechanism 75 includes a second linear module 751, which is connected to a support frame of the reagent chamber 7, and the support frame supports and fixes the second linear module 751. It also includes a second clamping jaw 754 connected to the second linear module 751, and the second linear module 751 can drive the second clamping jaw 754 to move in the X-axis, Y-axis and Z-axis directions.
[0060] In some embodiments, the second transfer mechanism 75 further includes a second driving member 753, which is connected to the second clamping claw 754. The second driving member 753 can drive the second clamping claw 754 to clamp the small reagent bottle 77, and then transfer the position of the small reagent bottle 77 through the second linear module 751, so that the small reagent bottle 77 can be transferred from the reagent rack 74 to the small reagent transfer area. The second driving member 753 can be a driving cylinder or a driving motor, which can drive the second clamping claw 754 to clamp the small reagent bottle 77, and this application does not limit this.
[0061] In some embodiments, the second transfer mechanism 75 also includes a second motor 752, which is connected to the second linear module 751, and the output shaft of the second motor 752 is connected to the second driving member 753. The second motor 752 can drive the second driving member 753 to rotate, and then drive the second clamp 754 to rotate, and adjust the angle of the second clamp 754 so that the second clamp 754 can accurately grasp the small reagent bottle 77.
[0062] In some embodiments, a reagent inlet and outlet 72 is provided on the reagent compartment 7, and a reagent rack 74 is provided in the reagent compartment 7. The reagent rack 74 can accommodate multiple (for example, more than one hundred) small reagents. When the small reagents are used up, the small reagent bottles 77 are transferred to the reagent inlet and outlet 72 by the second transfer mechanism 75, and the staff takes out the small reagent bottles 77 from the reagent inlet and outlet 72; the staff places the replacement small reagent bottles 77 on the reagent inlet and outlet 72, and transfers the small reagent bottles 77 to the reagent rack 74 by the second transfer mechanism 75 to complete the replacement or replenishment of the small reagents.
[0063] In some embodiments, a second code scanning component 76 is provided in the reagent compartment 7, and the second code scanning component 76 is connected to the second driving member 753. Before the second driving member 753 grabs the small reagent bottle 77, the second code scanning component 76 scans the information on the small reagent bottle 77 and enters it into the reagent management system, and then transfers the small reagent to the corresponding position of the reagent rack 74 through the second transfer mechanism 75.
[0064] In some embodiments, the reagent chamber 7 includes a small reagent transfer area protruding toward the incubation area, and the small reagent transfer area is provided with a small reagent transfer mechanism 73. The small reagent transfer mechanism 73 includes a transfer lower support plate 731 for supporting reagent bottles. The transfer lower support plate 731 is connected to the insulation shell 71 of the reagent chamber 7, and the insulation shell 71 protrudes toward the incubation area. The reagent bottle is placed on the transfer lower support plate 731, waiting for the sampling needle in the incubation area to take samples.
[0065] In some embodiments, the small reagent transfer area is further provided with a transfer upper support plate 732 located directly above the transfer lower support plate 731, a gap for placing reagent bottles is left between the transfer upper support plate 732 and the transfer lower support plate 731, and the areas where the transfer upper support plate 732 and the transfer lower support plate 731 protrude from the heat preservation shell 71 are connected by a connecting plate 733, so that the transfer upper support plate 732, the transfer lower support plate 731 and the connecting plate 733 form a transfer cavity 734 connected to the reagent chamber 7. When the reagent needle needs to take a sample, the second transfer mechanism 75 transfers the reagent bottle to the transfer cavity 734, waiting for the sampling needle to take a sample.
[0066] In some embodiments, a sampling through hole 7321 is provided on the transfer upper support plate 732, and a reagent bottle is placed directly below the sampling through hole, and a reagent needle passes through the through hole for sampling. An opening membrane is provided in the sampling through hole 7321, and during the process of the reagent needle sampling, the reagent needle can pass through the opening of the opening membrane for sampling, and the opening membrane is a cross membrane, a rice film, etc.
[0067] In some embodiments, there are multiple sampling through holes 7321, which are arranged in a straight line on the transfer support plate 732, and a reagent bottle waiting for sampling can be placed under each sampling through hole 7321. Through the provision of multiple sampling through holes 7321, when a reagent bottle under one of the sampling through holes 7321 is being sampled, the reagent management system issues instructions to the second transfer mechanism 75, so that the second transfer mechanism 75 transfers the next reagent bottle to be sampled to the transfer cavity 734 in advance to wait for sampling. After the reagent needle completes one sampling, it can continuously sample another bottle of reagent, which saves the time of the second transfer mechanism 75 to transfer the reagent bottle, improves the efficiency of the reagent needle sampling in the incubation stage, improves the incubation efficiency of the staining system, shortens the processing time of a single glass slide 65, and improves the efficiency of the staining system in processing the glass slide 65.
[0068] See attached Figure 3 As shown, in some embodiments, a sample loading area, an impregnation area, an incubation area, and a sealing area are provided in the processing chamber. The sample loading area is used to load the glass slide 65 to which the sample has been attached, and input the information of the sample tissue on the glass slide 65 into the staining system; the impregnation area is used to impregnate the sample tissue; the incubation area incubates the sample tissue with a small reagent, the sealing area seals the glass slide 65, and the sample is unloaded through the sample loading area to complete the sample tissue staining process.
[0069] Unlike the prior art, with the fully automatic staining system of the present invention, the samples to be processed will not undergo all the reaction processes at the same position. Instead, by arranging the sample loading area, the impregnation area, the incubation area and the sealing area in different spaces in the processing chamber, the sample tissue is processed at different stages in different areas, so that the sample tissue is processed in an assembly line mode, the number of slides 65 that can be accommodated by the staining system at the same time can be increased, and the efficiency of the staining system in processing the slides 65 can also be increased. For example, the first batch of slides 65 have passed through the sample loading area, the impregnation area and the incubation area, and are sealed in the sealing area at this time. At the same time, the second batch of slides 65 have passed through the sample loading area and the impregnation area, and are incubated in the incubation area, and the third batch of slides 65 are impregnated in the impregnation area for impregnation treatment. After the first batch of slides 65 are sealed, they can be temporarily stored in the transfer waiting area 2 or unloaded through the sample loading area, the second batch of slides 65 that have completed incubation enter the sealing area for sealing, and the third batch of slides 65 that have completed impregnation enter the incubation area for incubation, and so on.
[0070] Compared with the traditional slide 65, the loading, staining and incubation are all in one area. Only when a batch of slides 65 are fully processed from loading to incubation to unloading, can the next batch of slides 65 be processed. The staining system of the present application can perform operations such as staining, incubation, and sealing on different slides 65 at the same time, forming an assembly line processing mode, greatly improving the efficiency of processing sample tissues, and increasing the number of slides 65 processed per unit time, thereby increasing the number of slides 65 processed by the staining system per day, solving the problem of small daily specimen processing capacity of current instruments.
[0071] See attached Figure 4-6 As shown, in some embodiments, the loading area is provided with a loading mechanism 1, and the loading mechanism 1 includes a loading table 11, and the loading table 11 is fixedly connected to the support frame of the staining system, and the loading table 11 is supported and fixed by the support frame. A loading fixing groove 12 is provided above the loading table 11, and the loading fixing groove 12 is fixedly connected to the loading table 11 through a loading bracket 13. The loading fixing groove 12 is used to support and fix the slide rack 6 equipped with a glass slide 65. During the loading process, the technician can place the slide rack 6 equipped with the glass slide 65 in the loading fixing groove 12.
[0072] In some embodiments, the sample loading area is also the sample unloading area. After the sample tissue on the glass slide 65 is loaded through the sample loading area, it is processed in different areas and finally returned to the sample loading fixing groove 12 of the sample loading area together with the slide rack 6. The technician can take out the staining system from the sample loading fixing groove 12 by taking out the slide rack 6 with the processed glass slide 65. The technician can unload the glass slide 65 on the same slide rack 6 at one time, which increases the workload of the staff in unloading and reduces the staff's work intensity.
[0073] In some embodiments, a gap is left between the bottom of the sample loading fixing groove 12 and the workbench, and a lifting hole is provided at the bottom of the sample loading fixing groove 12. The width of the lifting hole is smaller than the width of the fixing groove, and a groove bottom step is formed between the lifting hole and the bottom of the fixing groove, and the slide rack 6 is supported by the groove bottom step.
[0074] See attached Figure 5 and attached Figure 6 As shown, in some embodiments, the fully automatic dyeing system of the present invention also includes a drive assembly 14 arranged on the sample loading workbench 11, and the drive assembly 14 includes a slide rail 142 arranged on the sample loading workbench 11 and a slider 143 that can slide along the slide rail 142, and the slide rail 142 is arranged in parallel with the length direction of the sample loading fixed groove 12. The drive assembly 14 also includes a sample loading drive motor 141 arranged on the sample loading workbench 11, and the sample loading drive motor 141 is connected to the slider 143, and the sample loading drive motor 141 can drive the slider 143 to slide along the slide rail 142. A lifting code scanning support plate 144 is arranged on the slide rail 142, and the slide rail 142 can drive the lifting code scanning support plate 144 to slide synchronously along the slide rail 142. A lifting assembly 15 is arranged at one end of the lifting code scanning support plate 144 close to the sample loading fixed groove 12, and the lifting assembly 15 can slide along the slide rail 142 with the lifting code scanning support plate 144 under the action of the drive motor. A first code scanning assembly 16 is disposed at the other end of the lifting code scanning support plate 144 , and the lifting code scanning support plate 144 can drive the lifting assembly 15 and the first code scanning assembly 16 to slide synchronously along the slide rail 142 .
[0075] See attached Figure 5As shown, the lifting assembly 15 is located in the gap directly below the sample fixing groove 12. When the lifting assembly 15 slides along the slide rail 142, the glass slide 65 on the slide rack 6 can be lifted up in sequence, so that the glass slide 65 can move vertically upward. During the upward movement of the lifted glass slide 65, its height is higher than that of other glass slides 65. The QR code on the lifted glass slide 65 is scanned by the first code scanning assembly 16, and the sample tissue information on the glass slide 65 is input into the staining system. Since the lifting assembly 15 and the first code scanning assembly 16 are connected to the same lifting code scanning support plate 144, the position between the lifting assembly 15 and the first code scanning assembly 16 is relatively fixed, ensuring that the distance between the first code scanning assembly 16 and each lifted glass slide 65 is the same, ensuring that the QR code of each lifted glass slide 65 can be clearly scanned.
[0076] See attached Figure 6 As shown, the lifting assembly 15 includes a lifting cylinder 151 fixedly connected to the lifting code scanning support plate 144, and a lifting member 152 is arranged on the telescopic rod of the lifting cylinder 151, and the lifting cylinder 151 can drive the lifting member 152 to move up and down. A limiting groove 153 is arranged at one end of the lifting member 152 close to the sample loading fixed groove 12, and the limiting groove 153 is a "V"-shaped structure that is wide at the top and narrow at the bottom. In the process of lifting the glass slide 65, the glass slide 65 is located in the limiting groove 153, and the glass slide 65 is guided and limited by the limiting groove 153, ensuring that the lifting member 152 can accurately lift the glass slide 65.
[0077] In some embodiments, one or more sample loading fixed slots 12 are provided, and each sample loading fixed slot 12 is to be provided with a corresponding first code scanning component 16 to enter the information of the glass slide 65 in the fixed slot. Exemplarily, one, two, three, or four sample loading fixed slots 12 can be provided, which are specifically determined according to the processing capacity and loading speed of the staining system. The more sample loading fixed slots 12 are provided, the higher the loading efficiency is, and accordingly, the larger the internal space of the staining system occupied by the loading mechanism 1 is. In this embodiment, in combination with factors such as the processing speed of the staining system, the loading efficiency, and the space occupied by the loading mechanism 1, the number of sample loading fixed slots 12 provided is two.
[0078] In some embodiments, the first code scanning component 16 is electrically connected to the control system of the staining system. The first code scanning component 16 transmits the code scanning information to the control system. The control system analyzes the code scanning information, such as analyzing the staining liquid suitable for the sample tissue on the glass slide. If it is found that the sample tissue on the same slide rack cannot be suitable for the same staining liquid, the control system will activate the alarm system, sound an alarm through the status light, etc., and wait for the technician to handle it.
[0079] In some embodiments, the slide rack 6 is a universal staining rack for technicians to pre-process samples outside the staining system. The technicians need to pre-process the sample tissue. During the pre-processing process, after the technicians process the sample tissue on a glass slide 65, they place the glass slide 65 on a universal staining rack in the laboratory and fix it, and then process the next glass slide 65. After the pre-processing of a batch of glass slides 65 is completed, the glass slide 65 is loaded into the staining system for processing. In the process of loading samples in the traditional staining system, the technicians transfer the glass slides 65 on the universal slide rack 6 in the laboratory to the dedicated slide rack 6 of the staining system or the incubation room in turn. Therefore, it is necessary to set up several dedicated transfer racks separately in the staining system, which wastes the internal space of the staining system and wastes a lot of manpower and time. In addition, in order to match the staining rack matched with the staining system, the cost of consumables is increased. For example, if there are 30 glass slides 65 on a slide rack 6, the technicians need to transfer 30 glass slides 65 in turn 30 times before all the glass slides 65 on a slide rack 6 can be transferred to the staining system. The staining system of the present application directly uses the existing universal slide rack 6 as a carrier for the turnover of glass slides within the staining system. After the technician completes the pre-treatment of the sample, the universal slide rack 6 loaded with glass slides 65 is directly loaded, and the slide rack 6 and several glass slides 65 are placed in the sample loading fixed groove 12 at one time, without relying on the special transfer carrier equipped with the staining system, which greatly improves the space utilization rate inside the staining system, improves the floor efficiency ratio of the staining system, and reduces the labor burden and the turnover time of the glass slides. In addition, by using the universal slide rack 6 of the hospital, there is no need to specially equip the staining rack with a special slide rack 6, which reduces the consumables cost of the staining system.
[0080] Alternatively, the slide rack 6 provided in the staining system is a commonly used slide rack in laboratories, which can be used by experimenters to fix slides outside the staining system, and can be used as a commonly used slide rack in hospitals, thereby reducing the consumables cost of purchasing the slide rack 6 in hospitals.
[0081] See attached Fig.16 As shown, in some embodiments, the slide rack 6 includes two fixing plates 61 disposed at the ends, and the two fixing plates 61 at the ends are connected by a plurality of fixing rods 62 disposed in parallel, and the fixing rods 62 fix the glass slide 65 in the left and right directions. A plurality of spacer blocks 63 are disposed symmetrically on the fixing rods 62, and the glass slide 65 is placed between adjacent spacer blocks 63. Through the provision of the spacer blocks 63, a certain distance is ensured between two adjacent glass slides 65, so that the adjacent glass slides 65 will not be contaminated with each other, and in the later staining process, the sample tissue on each glass slide 65 can be immersed in the macroreagent.
[0082] In some embodiments, stopper protrusions 64 are disposed on the outer sides of the two fixing plates 61, and the stopper protrusions 64 are disposed near the upper ends of the fixing plates 61. By disposing the stopper protrusions 64, the first transfer mechanism 5 prevents the slide rack 6 from falling off from the first transfer mechanism 5 during the process of clamping the slide rack 6, thereby increasing the safety of the slide 65 during the transfer process.
[0083] The slide rack 6 is composed of a fixing plate 61 and a fixing rod 62, and has a simple structure and light weight, which reduces the workload of technicians when loading and unloading samples. In the staining system, when the slide rack 6 is transferred, the power of the first transfer mechanism 5 is reduced.
[0084] In some embodiments, the first transfer mechanism 5 includes a first linear module 51, which is connected to a frame and supported and fixed by the frame. It also includes a first clamp 53 connected to the first linear module 51, which is a three-axis linear module that can drive the first clamp 53 to move in the X-axis, Y-axis and Z-axis directions. It is used to transfer the slide rack 6 from the loading workbench 11 to the transfer waiting area 2, and from the transfer waiting area 2 to the drying and dyeing mechanism 3; or transfer the glass slide that has been incubated and loaded on the slide rack 6 to the drying and dyeing mechanism again, or transfer it to the transfer waiting area 2, and transport the slide rack 6 to the loading mechanism 1 for unloading.
[0085] In some embodiments, the first transfer mechanism 5 also includes a clamping rotation assembly 52, which connects the first linear module 51 and the first clamp, can drive the first clamp 53 to clamp the slide rack 6 and can rotate the slide rack 6 to change the direction of the slide rack 6.
[0086] See attached Figure 10-15 As shown, in some embodiments, the clamping rotation assembly 52 includes a first motor 521 and a first gear 522, the output shaft of the first motor 521 is connected to the first gear 522, and the first motor 521 can drive the first gear 522 to rotate. The first clamping jaw 53 includes two symmetrically arranged clamping jaws, and the clamping jaws include a clamping portion 531 for clamping the slide rack 6, and a connecting portion 532 connected to the first gear 522. A linearly arranged sawtooth 533 is provided on one side of the connecting portion 532 close to the first gear 522, and the sawtooth 533 respectively connected to the two clamping jaws is located on the opposite sides of the first gear 522, and is respectively meshed with the first gear 522. During the rotation of the first gear 522, the sawtooth 533 drives the two clamping jaws to move closer or farther from each other, and then the slide rack 6 is clamped or loosened through the clamping portion 531, so that the first clamping jaw can clamp the slide rack 6.
[0087] In some embodiments, the clamping rotating assembly 52 also includes a guide member 523, which is provided with two parallel guide grooves 5231, and the connecting portion 532 is arranged in the guide groove 5231. When the connecting portion 532 moves toward each other under the action of the first gear 522, the connecting portion 532 moves in the guide groove 5231 along the guide groove 5231, which is more stable.
[0088] The guide member 523 is provided with a position-avoiding groove 5232, the position of which matches the position of the first gear 522, the position-avoiding groove 5232 and the guide groove 5231 are connected, the first gear 522 is accommodated in the position-avoiding groove 5232, and can drive the first clamping claw 53 to clamp the slide rack 6 through the sawtooth 533. Through the arrangement of the guide member 523, the connecting portion 532 moves along the guide groove 5231 in the guide groove 5231 more stably; and the position-avoiding groove 5232 is provided to accommodate the first gear 522, so that the first gear 522 drives the first clamping claw 53 to clamp the slide rack 6 more safely.
[0089] After the clamping rotating assembly 52 drives the first clamping claw 53 to clamp the slide rack 6, the first linear module 51 drives the slide rack 6 and the glass slide 65 to transfer. After being transferred to another processing area, the first motor 521 drives the clamping rotating assembly 52 to continue rotating through the rotating shaft, which can drive the first clamping claw to clamp the slide rack 6 and continue rotating, adjust the angle of the slide rack 6, and enable the slide rack 6 to be accurately placed in another processing area. By setting the clamping rotating assembly 52, the action of clamping the slide rack 6 and the action of adjusting the angle of the slide rack 6 can be completed. One assembly completes multiple functions, reducing the parts of the first transfer mechanism 5, making the structure of the first transfer mechanism 5 simpler, and reducing the manufacturing cost.
[0090] See attached Figure 3 and attached Figure 8 As shown, in some embodiments, a drying and dyeing mechanism 3 is provided in the dyeing area, and the drying and dyeing mechanism 3 includes a drying and dyeing tank 31, and the length, width and height of the drying and dyeing tank 31 are respectively greater than the length, width and height of the slide rack 6. The glass slide 65 on the slide rack 6 is transferred to the drying and dyeing tank 31 as a whole through the first transfer mechanism 5, and can be accommodated in the drying and dyeing tank 31 as a whole. In the process of transferring the glass slide 65, the first transfer mechanism 5 transfers together with the slide rack 6, and can transfer multiple (30) glass slides 65 at one time, realizing batch transfer of the glass slides 65, improving the transfer efficiency at different processing stages, and thus improving the processing efficiency of the staining system.
[0091] In some embodiments, a plurality of slides 65 on the slide rack 6 can be simultaneously accommodated in the drying and dyeing tank 31. The drying and dyeing tank 31 is first heated, and then the slides 65 in the tank are heated to achieve the purpose of baking. By setting the drying and dyeing tank 31, the technician does not need to bake the slides during the pre-treatment of the slides 65 outside the staining system. The staining system of the present invention can automatically bake the slides after loading the sample, saving the workload of the technicians in pre-treatment, and no baking machine is required in the laboratory, saving the purchase cost and floor space of the baking machine.
[0092] In some embodiments, the drying and dyeing tank is provided with an inlet and outlet liquid channel 34, and a large reagent can be input into the drying and dyeing tank to dye the sample tissue on the glass slide 65 in the dyeing tank, thereby completing the first dyeing of the sample tissue. By dyeing 30 glass slides 65 on a slide rack 6 at the same time, the first dyeing efficiency of the glass slide 65 can be improved compared with the current single-slide dripping or single-slide immersion. In the process of the first code scanning component 16 scanning the QR code of the glass slide 65, it has been ensured that the sample tissue on the same slide rack 6 is suitable for the same large reagent when being dyed. If there is a sample tissue that is not suitable for the same large reagent, the control system will alarm and wait for the staff to handle it to ensure that the glass slide 65 on the same slide rack 6 is suitable for the same large reagent.
[0093] In some embodiments, the shape of the drying and immersion tank is compatible with the shape of the slide rack 6 for loading the glass slide 65. In this embodiment, the drying and immersion tank is narrow at the bottom and wide at the top, which is compatible with the slide rack 6, and can save the amount of large reagents.
[0094] In some embodiments, a dyeing cover 32 is provided above the drying and dyeing tank. During the drying or dyeing process, the dyeing cover 32 can be automatically closed by driving the cylinder 33 to improve the drying efficiency and prevent the volatilization of large reagents during the dyeing stage.
[0095] See attached Figure 3 , Attachment Figure 9a , Attachment Figure 9b As shown, in some embodiments, the sealing area is provided with a sealing mechanism 4, which includes a lifting assembly 41, which is connected to the slide rack 6, and the slide 65 in the slide rack 6 is in a horizontal position. The lifting assembly 41 can change the vertical height of the slide rack 6, thereby changing the height of the slide on the slide rack 6.
[0096] In some embodiments, the sealing mechanism 4 includes an ejection assembly 42, and the ejection assembly 42 is flush with the glass slide 65 to be sealed on the glass slide rack 6. The ejection assembly 42 ejects the glass slide 65 to the sealing assembly 43 for sealing. When the sealing is completed, the ejection assembly 42 resets the glass slide 65 to the glass slide rack 6. At this time, the height of the glass slide rack 6 is adjusted by the lifting assembly 41 so that the next glass slide 65 to be sealed is flush with the ejection mechanism.
[0097] In some embodiments, the sealing mechanism 4 further includes an adsorption assembly 44 for adsorbing the glass slide 65 cover from the groove body 45 for receiving the glass slide 65 cover to the sealing assembly 43 to seal the glass slide 65 .
[0098] By setting up the sealing mechanism 4, the sealing work of the glass slide 65 can be completed in the staining system, and the technicians do not need to do post-processing of the sealing outside the staining system, which saves the technicians' post-processing workload, and at the same time saves the laboratory's cost of purchasing a sealing machine and saves the floor space occupied by the sealing machine.
[0099] The dyeing system of the present application has the functions of baking and sealing the slices by setting up a drying and dyeing mechanism 3 and a sealing mechanism 4. The dyeing system is an all-in-one machine for baking, dyeing and sealing the slices, which makes the dyeing system have more automated functions and can save the workload of technical personnel in pre-processing and post-processing.
[0100] In some embodiments, a large-capacity reagent area 100 and a waste liquid area 200 are also included. The large-capacity reagent area 100 can accommodate multiple large-capacity reagent bottles to reduce the frequency of replenishing large-capacity reagents, and the large-capacity reagent area 100 is provided with a liquid shortage alarm system, which automatically alarms when the large-capacity reagent is short of liquid, and replenishes liquid without stopping the machine. The waste liquid area 200 can accommodate large-capacity waste liquid bottles, reduce the frequency of pouring out waste liquid, and increase the time that staff members leave the machine.
[0101] In some embodiments, the support frame divides the staining system into multiple areas, including a waste liquid area 200 and a large-capacity reagent area 100 located at the bottom layer. Since the large-capacity reagent in the large-capacity reagent area 100 and the waste liquid in the waste liquid area 200 are relatively large, placing them at the bottom layer lowers the center of gravity of the staining system, making the staining system more stable. Placing them at the bottom layer is conducive to adding large-capacity reagents and pouring out waste liquids, making replacement more labor-saving.
[0102] In some embodiments, the volume of the large-capacity reagent bottles in the large-capacity reagent area 100 can be set larger, for example, 1L, 5L or 10L, so as to meet the high-throughput and unattended use requirements of the staining system, and avoid having to interrupt the staining system due to the need to stop and add large-capacity reagents due to excessive sample processing volume, thereby reducing the impact of human factors on the staining process and ensuring the stability of the preparation process.
[0103] In some embodiments, a first working area 300 is arranged directly above the large-capacity reagent area 100, and the first working area 300 is provided with a sample loading area, a waiting area, a drying and immersion area, and a sealing area. By setting the drying and immersion area for using large-capacity reagents directly above the large-capacity reagents, the distance between the large-capacity reagents and the drying and immersion tank is shortened, and the pipeline channel between the large-capacity reagents and the drying and immersion tank is shortened, the pipeline cost is reduced, and the waste of large-capacity reagents in the pipeline is reduced. A second working area 400 is arranged above the first working area 300, and an incubation area is arranged in the second working area 400. The first working area 300 and the second working area 400 transport the slide rack 6 and the glass slide 65 through the elevator 81. The first working area 300 and the second working area 400 are arranged in layers in height, which reduces the floor space occupied by the staining system and improves the floor efficiency ratio of the staining system. In addition, by placing the loading area close to the waiting area and the drying and impregnation area, it is more convenient for the dyeing system to pre-process the sample. The present application integrates the drying and impregnation area and the sealing area for pre-processing and post-processing the sample in one area, and realizes the centralization of the internal area of the dyeing system to the greatest extent. By placing the sealing area and the drying and impregnation area close to the transfer waiting area, it is convenient to temporarily store the finally processed sample in the transfer waiting area without frequently opening and closing the door of the dyeing system. In other embodiments, the specific functional areas in the first working area 300 and the second working area 400 can adopt other layout methods.
[0104] In some embodiments, a small reagent area 500 is provided in the processing chamber, and the small reagent area 500 is provided on one side of the second working area 400. By providing the small reagent area 500 on one side of the second working area, it is ensured that the sampling mechanism located in the second working area can conveniently perform sampling in the small reagent area.
[0105] In some embodiments, the fully automatic staining system of the present invention also includes a film scanning mechanism, which is used to scan and photograph the film before sealing, and store the photo information in the management system of the staining system, thereby facilitating the fully automatic staining system to electronically present the film production results. The present application is conducive to improving the quality of digital images by setting up a film scanning mechanism to scan the film before sealing. The staining system of the present application can complete image digital scanning and conventional physical sealing under the premise of high-throughput film output. The function call of the film scanning mechanism can be selected according to actual needs. Working process: The pre-treated glass slide (referring to the glass slide with the sample attached to the surface of the glass slide) is placed on the slide rack, and the slide rack is used to load the sample to the loading mechanism. The loading mechanism scans the information of the sample tissue on the glass slide and transmits it to the control system. The glass slide that has completed the loading is transferred to the drying and staining area through the first transfer mechanism along with the slide rack, and the sample tissue on the glass slide is dried and stained by the drying and staining mechanism; if there are glass slides being processed in the drying and staining area, the glass slide that has completed the loading is transferred to the transfer waiting area 2 along with the slide rack through the first transfer mechanism, and enters the drying and staining area after waiting for the drying and staining area to complete the processing.
[0106] The glass slides that have been dried and stained are transported by the elevator 81 to the incubation area for incubation; after the incubation is completed, the glass slides of the previous glass slide rack are returned to the first working area by the elevator again, and then transferred to the sealing mechanism by the first transfer mechanism for sealing. It should be noted that in the processing chamber, multiple rounds of slide preparation procedures are carried out simultaneously. For example, after the previous glass slide rack has been sent out from the immersion area, the glass slides of the next glass slide rack are sent to the immersion area; after the previous glass slide rack has been sent back from the incubation area to the first working area, the glass slides of the next glass slide rack are sent from the immersion area to the incubation area, and the subsequent glass slide rack is sent to the empty immersion area. In this way, multiple rounds of glass slide staining and / or sealing processing are achieved.
[0107] After the sealing is completed, the slides are transferred through the first transfer mechanism into the transfer waiting area 2 to wait for sample unloading, or into the sample loading area to wait for the staff to take out the processed slides and the slide rack as a whole.
[0108] In the description of the present invention, it should be understood that the terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include at least one of the features. In the description of the present invention, the meaning of "plurality" is at least two, such as two, three, etc., unless otherwise clearly and specifically defined.
[0109] The above implementation modes are only for illustrating the technical concept and features of the present invention, and their purpose is to enable people familiar with this technology to understand the content of the present invention and implement it, and they cannot be used to limit the protection scope of the present invention. Any equivalent changes or modifications made according to the spirit of the present invention should be included in the protection scope of the present invention.
Claims
1. A fully automatic dyeing system, comprising a processing chamber, wherein an incubation area is arranged in the processing chamber, wherein the incubation area is arranged with a plurality of incubation positions, and the number of the incubation positions is n, characterized in that: Also includes: A transfer waiting area, which is arranged in the processing chamber and is used to place slides to be processed and slides to be sent out after processing. Before the fully automatic staining system starts working, the number of slides located in the transfer waiting area is N, and N / n≥1; A reagent warehouse is arranged in the processing chamber, a refrigeration mechanism is arranged in the reagent warehouse, and the reagent warehouse can accommodate several kinds of small reagents.
2. The fully automatic dyeing system according to claim 1, characterized in that: The transfer waiting area is provided with a waiting fixing groove, and the waiting fixing groove can fix the glass slide to be processed. There are multiple waiting fixing grooves, and each of the waiting fixing grooves can accommodate at least one slide rack with a glass slide.
3. The fully automatic dyeing system according to claim 1, characterized in that: The reagent compartment is provided with a second transfer mechanism and a small reagent transfer mechanism, and the second transfer mechanism can transfer the small reagent to the small reagent transfer mechanism to wait for the sampling mechanism to perform sampling.
4. The fully automatic dyeing system according to claim 3, characterized in that: The small reagent transfer mechanism includes a transfer support plate, which forms a transfer cavity connected to the interior of the reagent compartment. Small reagents can be accommodated in the transfer cavity under the action of the second transfer mechanism. A plurality of sampling through holes are provided on the transfer support plate, and the sampling mechanism can sample through the sampling through holes.
5. The fully automatic dyeing system according to claim 3, characterized in that: The second transfer mechanism includes a second linear module, which is connected to the insulating shell of the reagent chamber, and also includes a second clamp connected to the second linear module. The second linear module can drive the second clamp to move in the X-axis, Y-axis and Z-axis directions, and the second clamp can clamp a small reagent bottle.
6. The fully automatic dyeing system according to claim 5, characterized in that: The second transfer mechanism also includes a second driving member, which is connected to the second clamp, and the second driving member can drive the second clamp to clamp the small reagent bottle, and then transfer the position of the small reagent bottle through the second linear module; the second transfer mechanism also includes a second motor, which is connected to the second linear module, and the output shaft of the second motor is connected to the second driving member, and the second motor can drive the second clamp to rotate by driving the second driving member to rotate.
7. The fully automatic dyeing system according to claim 3, characterized in that: The reagent compartment is provided with a reagent inlet and outlet, a reagent rack is provided in the reagent compartment, and the reagent rack can accommodate hundreds of small reagents. The second transfer mechanism can transfer the reagents located at the reagent inlet and outlet and the small reagent bottles located on the reagent rack.
8. The fully automatic dyeing system according to claim 3, characterized in that: A second code scanning component is arranged in the reagent compartment, and the second code scanning component is connected to the second transfer mechanism. The second code scanning component can scan the information on the small reagent bottle and enter it into the reagent management system.
9. The fully automatic dyeing system according to claim 1, characterized in that: The processing chamber is provided with a sample loading area, a staining area, an incubation area and a sealing area. The slide can be transferred between different areas through a first transfer mechanism, and different stages of processing can be performed in different areas.
10. The fully automatic dyeing system according to claim 9, characterized in that: A sample loading mechanism is arranged in the sample loading area, and the sample loading mechanism comprises a sample loading fixing groove, and the sample loading fixing groove can accommodate a slide glass rack equipped with a glass slide.
11. The fully automatic dyeing system according to claim 10, characterized in that: The sample loading mechanism includes a lifting component and a first code scanning component. The lifting component can drive the glass slide to move upward, and the first code scanning component can scan the glass slide driven by the lifting component.
12. The fully automatic dyeing system according to claim 111, characterized in that: It also includes a driving component, which can drive the lifting component and the first code scanning component to move synchronously.
13. The fully automatic dyeing system according to claim 12, characterized in that: The lifting assembly includes a lifting cylinder fixedly connected to the driving assembly, a lifting piece is arranged on the telescopic rod of the lifting cylinder, the lifting cylinder can drive the lifting piece to move up and down, a limiting groove is arranged at one end of the lifting piece close to the sample fixing groove, and during the process of the lifting assembly lifting the glass slide, a partial area of the lifted glass slide is accommodated in the limiting groove.
14. The fully automatic dyeing system according to claim 9, characterized in that: A drying and dipping mechanism is provided in the dipping area, and the drying and dipping mechanism comprises a drying and dipping tank. The glass slides on the slide rack are transferred as a whole to the drying and dipping tank through the first transfer mechanism, and can be accommodated as a whole in the drying and dipping tank for baking or dipping.
15. The fully automatic dyeing system according to claim 2, characterized in that: The slide rack comprises two fixing plates arranged at the ends, and stop protrusions are arranged on the outer sides of the two fixing plates, and the stop protrusions are arranged close to the upper ends of the fixing plates.
16. The fully automatic dyeing system according to claim 9, characterized in that: The first transfer mechanism includes a first linear module and a first clamp connected to the first linear module. The first linear module is a three-axis linear module that can drive the first clamp to move in the X-axis, Y-axis and Z-axis directions.
17. The fully automatic dyeing system according to claim 16, characterized in that: The first transfer mechanism also includes a clamping rotation component connecting the first linear module and the first clamping jaw. The clamping rotation component can drive the first clamping jaw to clamp the slide rack and can rotate the slide rack to change the angle of the slide rack.
18. The fully automatic dyeing system according to claim 17, characterized in that: The clamping rotation assembly includes a first motor and a first gear, the output shaft of the first motor is connected to the first gear, the first motor can drive the first gear to rotate, the first clamp includes two symmetrically arranged clamp members, the clamp member includes a clamping portion for clamping the slide rack, and a connecting portion connected to the first gear, a linearly arranged sawtooth is provided on one side of the connecting portion close to the first gear, the saw teeth respectively connected to the two clamp members are located on opposite sides of the first gear, and are respectively meshed with the first gear, and during the rotation of the first gear, the two clamp members can be driven to approach or move away from each other through the saw teeth.
19. The fully automatic dyeing system according to claim 18, characterized in that: It also includes a film scanning mechanism, which can scan and photograph the film before sealing, and store the photo information in the management system of the staining system.
20. The fully automatic dyeing system according to any one of claims 1 to 19, characterized in that: A waste liquid area and a large-capacity reagent area are arranged at the bottom layer of the processing chamber, a first working area is arranged above the large-capacity reagent area, at least one of a loading area, a transfer waiting area, a drying and staining area and a sealing area is arranged on the first working area, a second working area is arranged above the first working area, and at least an incubation area is arranged in the second working area.
21. A dyeing process, based on the fully automatic dyeing system according to any one of claims 1 to 20, characterized in that: The dyeing process comprises the following steps which are performed continuously and uninterruptedly: S1: In the first working area, a slide rack carrying a slide is loaded onto a loading mechanism; S2: Directly transfer the slide rack to the transfer waiting area to wait for processing; S3: placing the first slide rack carrying the slides into the drying and staining mechanism, and performing batch baking and antigen repair on the slides; S4: transporting the first slide rack to a second working area, wherein the second working area is at a different height from the first working area; S5: sending the glass slides on the first glass slide rack to the incubation mechanism for incubation in sequence, and placing the second glass slide rack carrying the glass slides into the drying and staining mechanism; S6: Recover the glass slides on the first glass slide rack from the incubation mechanism to the first glass slide rack and then transport them back to the first working area, transport the second glass slide rack carrying the glass slides to the second working area for incubation; place the third glass slide rack carrying the glass slides into the drying and staining mechanism; S7: After sealing the first slide rack carrying the slides in the first working area, the first slide rack is transported to the transfer waiting area; the slides on the second slide rack are recovered to the second slide rack and then transported back to the first working area for sealing; the third slide rack carrying the slides is transported to the second working area for incubation, and the fourth slide rack carrying the slides is transported from the transfer waiting area to the drying and staining mechanism, thereby continuously repeating the above steps S3-S6.
Citation Information
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