Integrated immunohistochemistry and fluorescence in situ hybridization staining machine with quality control

By integrating immunohistochemistry and fluorescence in situ hybridization into the instrument, the problems of high cost and large footprint caused by the separation of existing equipment have been solved, and the automation of the laboratory and the improvement of work efficiency have been achieved.

CN119827265BActive Publication Date: 2026-01-06图凌(杭州)生物医药有限公司
View PDF 2 Cites 0 Cited by

Patent Information

Application Number
CN202510006265.0
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2025-01-03
Publication Date
2026-01-06
Estimated Expiration
2045-01-03

AI Technical Summary

Technical Problem

The existing immunohistochemistry quality control instruments and fluorescence in situ hybridization instruments are separate devices, resulting in high equipment procurement costs, large space requirements, and additional sample transport operations, which affect work efficiency.

Method used

Design an integrated immunohistochemistry and fluorescence in situ hybridization staining machine with quality control, integrating reaction module, sample loading module, reagent storage module, sample needle storage module, sample needle disposal module, quality control calibration module and quality control calibration tray to realize automated operation of immunohistochemistry experiment and fluorescence in situ hybridization.

Benefits of technology

It has improved the level of laboratory automation, reduced the laboratory footprint, and increased work efficiency through automated operation, prevented contamination, and simplified the design of sample dispensing procedures.

✦ Generated by Eureka AI based on patent content.

Smart Images

  • Figure 0LKUMF9N1FSOTJ3EAP2ZYEGYFNA1TU46IUDOYROK
    Figure 0LKUMF9N1FSOTJ3EAP2ZYEGYFNA1TU46IUDOYROK
  • Figure BIAJ8WT7KFG32KZA4YIDYT6NJVV12MKNIGLJORZO
    Figure BIAJ8WT7KFG32KZA4YIDYT6NJVV12MKNIGLJORZO
  • Figure BZVE5VBGP7GKN8CPSIXIKYZXRC1T9DSM2JELL94I
    Figure BZVE5VBGP7GKN8CPSIXIKYZXRC1T9DSM2JELL94I
Patent Text Reader

Abstract

The application discloses a quality control integrated immunohistochemical and fluorescence in situ hybridization staining machine, comprising a plurality of reaction modules, a sample adding module, a reagent storage module, a sample adding needle storage module, a sample adding needle discarding module, a quality control calibration module and a quality control calibration liquid tray arranged in a machine box. The application integrates a series of automatic operations from quality control to staining treatment of the immunohistochemical experiment and fluorescence in situ hybridization in one device, improves the laboratory automation degree, and reduces the laboratory floor space.
Need to check novelty before this filing date? Find Prior Art

Description

Technical Field

[0001] This invention relates to the field of laboratory instruments, and in particular to an instrument that integrates immunohistochemical quality control, automated staining processing, and fluorescence in situ hybridization functions. Background Technology

[0002] Immunohistochemistry (IHCC) is a technique that applies the fundamental principles of immunology—antigen-antibody reactions, specifically the specific binding of antigens and antibodies—to identify antigenic peptides and proteins within tissue cells through chemical reactions that allow labeled antibodies to develop color using chromogenic agents such as fluorescein, enzymes, metal ions, or isotopes. It enables the localization, qualitative analysis, and relative quantification of these antigens. Immunohistochemical quality control systems and staining instruments are fully automated instruments used in immunohistochemistry.

[0003] Fluorescence in situ hybridization (FISH) is a molecular biology technique that uses fluorescently labeled nucleic acid probes to hybridize with target nucleic acid sequences in a sample to detect and locate specific DNA or RNA sequences. The most important factors in FISH are temperature, light, humidity, and the pH of various reagents. Temperature and humidity directly affect the hybridization efficiency between the probe and the target DNA; light affects the intensity of the fluorescent dye, therefore probes must be stored in the dark, and hybridized slides can be mounted with an anti-fluorescence quencher and stored in the dark; the pH of various reagents must also be precisely met, which directly affects the stability of FISH. Existing immunohistochemistry quality control instruments and immunohistochemistry staining instruments are separate devices, lacking integrated systems. This results in high equipment procurement costs, large space requirements, and additional sample transport operations, impacting work efficiency. Summary of the Invention

[0004] The present invention aims to overcome the above-mentioned shortcomings of existing instruments and equipment by providing an integrated immunohistochemistry and fluorescence in situ hybridization staining machine with quality control.

[0005] To achieve the above objectives, the present invention adopts the following technical solution:

[0006] This application discloses an integrated immunohistochemistry and fluorescence in situ hybridization staining machine with quality control, comprising several reaction modules, sample loading modules, reagent storage modules, sample needle storage modules, sample needle disposal modules, quality control calibration modules, and quality control calibration trays, all housed within the machine casing.

[0007] The sample dispensing module includes a sample dispensing robotic arm and a replaceable sample dispensing needle assembly. The end of the sample dispensing robotic arm is equipped with an electromagnet suction head, a negative pressure suction tube, and a negative pressure pump connected to the negative pressure suction tube. The negative pressure pump is connected to the negative pressure suction tube, and the electromagnet suction head is located on one side of the negative pressure suction tube. The sample dispensing needle assembly includes a needle head and a connecting part. The connecting part is used to connect with the negative pressure suction tube, and the connecting part is also equipped with a first iron plate for the electromagnet suction head to attract.

[0008] The sample needle storage module is used to store replaceable sample needle assemblies, and the sample needle disposal module is used to store discarded replaceable sample needle assemblies.

[0009] The quality control calibration module includes a hollow calibration tube, a core column movably sleeved inside the calibration tube, and a calibration mounting part. The calibration mounting part is provided with a second iron plate for adsorption by an electromagnet head. The calibration mounting part is provided with a pipe communicating with the calibration tube. A second piston is provided at the upper end of the calibration tube. The movable second piston is located inside the pipe. A spring is also sleeved below the second piston in the calibration tube. The upper end of the core column passes through the second piston and is fixedly connected to the calibration mounting part.

[0010] Preferably, the connecting part is provided with a liquid storage chamber, and the liquid storage chamber is provided with a first piston that blocks the two ends of the liquid storage chamber. One end of the liquid storage chamber is connected to the needle head, and the other end of the liquid storage chamber is detachably connected to the negative pressure suction tube.

[0011] Preferably, the top of the connecting part is threaded with a threaded sleeve, and a sealing ring is embedded between the threaded sleeve and the connecting part. When the negative pressure suction tube is inserted into the connecting part, the side of the sealing ring is exposed and closely attached to the outer wall of the negative pressure suction tube; the top surface of the first iron plate is provided with several anti-slip stripes; the sample needle storage module is provided with a rotating fixture.

[0012] Preferably, each reaction module includes a slide tray, a tray loading track, a heating base, a pressing mechanism, a glass slide, and a liquid cover film.

[0013] The slide tray includes a long strip main tray and a long strip slide holder. The slide holder and the main tray are slidably connected, allowing the slide holder to slide out to one side perpendicular to the length of the main tray. The slide holder is used to hold slides, and the liquid cover film is detachably rotatably connected to the main tray.

[0014] The clamping mechanism is height-adjustable and mounted above the heating base. The pallet loading track is mounted below the clamping mechanism. The bottom of the main pallet and the pallet loading track are detachably and slidably connected, allowing the main pallet to slide between the connecting pallet loading track and the clamping mechanism.

[0015] The pressing mechanism is used to press down the liquid cover film to make it fit against the glass slide;

[0016] Each reaction module is equipped with an ejection mechanism, which is used to drive the slide holder to slide out or retract the main tray.

[0017] The main tray includes a first frame and a second frame;

[0018] The second frame structure is set inside the first frame and has rotating shafts at both ends that are rotatably connected to the first frame; the slide holder has positioning grooves for arranging and placing slides, the bottom of the slide holder is slidably connected to the second frame, and the second frame has a buckle on the other side away from the sliding direction of the slide holder, and the buckle and the liquid cover film correspond one-to-one.

[0019] The bottom of the first frame is slidably connected to the tray loading track. The first frame includes a first limiting beam and a second limiting beam located on both sides of the rotating shaft and extending along the direction of the tray loading track. The first limiting beam is located on the side of the slide holder sliding out direction and is used to limit the slide holder to be placed horizontally when the second frame rotates to this side at the maximum angle. The second limiting beam is located on the side away from the slide holder sliding out direction and is used to limit the maximum tilt angle of the slide holder when the second frame rotates to this side.

[0020] The liquid cover film is provided with a handle end with a rotating shaft structure. The buckle is used to rotate and connect the handle end of the liquid cover film, so that the liquid cover film covers one by one on the glass slide and the liquid cover film can be flipped upward relative to the second frame.

[0021] The slide holder has guide protrusions on both sides corresponding to each liquid cover film, and the guide protrusions are used to lift the liquid cover film when the slide holder slides out.

[0022] Preferably, a light shield is provided on one side of the reaction module, and an opening for accommodating the reaction module is provided on one or both sides of the light shield; the light shield is connected to the inside of the chassis through an electrically controlled slide rail mechanism, which is used to drive the light shield to block the reaction module.

[0023] Preferably, the guide protrusion is lower on one side of the slide holder in the sliding direction than on the other side, so that its upper edge forms a bevel structure. The liquid cover film has limiting protrusions on both sides of its end, and the limiting protrusions overlap the upper edge of the guide protrusion.

[0024] Preferably, the clamping mechanism includes a cover disposed on the upper part and a spring pressure head disposed on the lower surface of the cover. The spring pressure head is located on the side of the second frame away from the slide holder when the rotating shaft is slid out. The clamping mechanism presses down to cause the spring pressure head to push the second frame downward to rotate to the maximum limit angle away from the slide holder when it is slid out.

[0025] Preferably, the clamping mechanism is provided with a cam mechanism at both ends, which is used to drive the clamping mechanism to rise and fall.

[0026] Preferably, the ejection mechanism includes an ejection frame and a pair of electromagnetic push rods. The ejection frame is located below the heating base of each reaction module and is slidably connected to the heating base. The electromagnetic push rods are located below the heating base and are connected to the ejection frame. A detachable connection structure is provided between the end of the ejection frame and the slide holder. The electromagnetic push rods are used to eject and retract the slide holder through the ejection frame.

[0027] Preferably, the detachable connection structure includes a first hook and a second hook. The first hook is provided on both sides of the end of the ejector frame, and the end of the first hook is a hook-shaped structure that bends towards the slide holder in the direction of sliding out and opens downward. The first hook located at the inner end in the direction of insertion of the main tray is further away from the main tray than the first hook at the other end. The second hook is provided below the slide holder in the direction of sliding out. The end of the second hook is a hook-shaped structure that bends towards the inner end in the direction of insertion of the main tray and is further away from the main tray than the second hook at the other end.

[0028] Therefore, the present invention has the following beneficial effects:

[0029] (1) The automation of a series of operations from quality control to staining in immunohistochemistry experiments, as well as fluorescence in situ hybridization, is integrated into one device, which improves the automation level of the laboratory and reduces the laboratory footprint.

[0030] (2) The slides in the slide tray are placed on the slide holder that can slide out. During the operation of adding samples for quality control, they will not be interfered with by the liquid cover film. At this time, the slides are in a horizontal state. When the slide holder is put into the main tray, the liquid cover film repeatedly covers the slides and works with the pressing mechanism to make the liquid cover film and the slides tilt at a certain angle at the same time, so as to facilitate the formation of liquid film by using the siphon principle.

[0031] (3) The end of the robotic arm and the replaceable needle assembly are automatically connected and disconnected; this allows for direct replacement of the needle assembly when switching between different experimental modes, preventing contamination; the reservoir provides additional space for reagent aspiration, ensuring uniform needle tip length, which not only facilitates storage within the device but also simplifies the design of the robotic arm positioning program, as it simplifies adjustments on the height coordinates. Furthermore, the first piston prevents reagent backflow into the negative pressure pipette, thus avoiding contamination.

[0032] (4) The quality control calibration module is also a component that can be magnetically adsorbed and disassembled. Its function is to dip into the hydrophobic liquid used for calibration in the quality control calibration liquid tray, which is usually paraffin. When pressed onto the surface of the glass slide, it can form a hollow ring calibration area. Attached Figure Description

[0033] Figure 1 This is a structural diagram of the integrated immunohistochemistry and fluorescence in situ hybridization staining machine with quality control according to the present invention.

[0034] Figure 2 This is a structural diagram of the sample dispensing robotic arm 201 and the replaceable sample dispensing needle assembly 202.

[0035] Figure 3 This is a structural diagram of the sample loading robotic arm 201 and the quality control calibration module 6.

[0036] Figure 4 This is a schematic diagram of the immunohistochemical staining process of the reaction module.

[0037] Figure 5 This is a schematic diagram of the reaction module during the quality control sample addition process.

[0038] Figure 6 This is an exploded view of the main tray and slide holder.

[0039] Figure 7 This is a cross-sectional view of the reaction module in the working state of immunohistochemical staining.

[0040] Figure 8 This is a cross-sectional view of the reaction module during the quality control sample addition process. Detailed Implementation

[0041] The present invention will be further described below with reference to the accompanying drawings and specific embodiments.

[0042] like Figure 1 As shown, this application discloses an integrated immunohistochemistry and fluorescence in situ hybridization staining machine with quality control, characterized in that it includes several reaction modules 1, sample loading modules 2, reagent storage modules 3, sample needle storage modules 4, sample needle disposal modules 9, quality control calibration modules 6, quality control calibration liquid trays 7, and movable light shields 8, all arranged inside the machine casing.

[0043] The sample application module 2 includes a sample application robotic arm 201 and a replaceable sample application needle assembly 202. The sample application robotic arm 201 is equipped with an electromagnet suction head 2011, a negative pressure suction tube 2012, and a negative pressure pump 2013 connected to the negative pressure suction tube. The negative pressure pump 2013 is connected to the negative pressure suction tube 2012. The electromagnet suction head 2011 is located on one side of the negative pressure suction tube 2012. The sample application needle assembly 202 includes a needle head 2021 and a connecting part 2022. The connecting part 2022 is used to connect with the negative pressure suction tube 2012. The connecting part 2022 is also provided with a first iron plate 2023 for adsorption by the electromagnet suction head 2011. The electromagnet suction head 2011 and the first iron plate 2023 achieve controllable magnetic adsorption, thereby enabling automatic connection and disassembly of the end of the sample dispensing robotic arm 201 and the replaceable sample dispensing needle assembly 202. This allows for direct replacement of the sample dispensing needle assembly 202 when switching to different experimental modes, preventing contamination. The sample dispensing robotic arm 201 can place the replaceable sample dispensing needle assembly 202 into the sample dispensing needle disposal module 9 for unified recycling and cleaning.

[0044] The sample needle storage module 4 is used to store the replaceable sample needle assembly 202, and the sample needle disposal module 9 is used to store the discarded replaceable sample needle assembly 202. After the experiment, the sample needles in the sample needle disposal module 9 can be taken out, cleaned, and then put back into the sample needle storage module 4 for the next use.

[0045] The quality control calibration module 6 includes a hollow calibration tube 601, a core column 602 movably sleeved inside the calibration tube 601, and a calibration mounting part 603. The calibration mounting part 603 is provided with a second iron sheet 6031 for adsorption by an electromagnet head 2011. The calibration mounting part 603 is provided with a pipe communicating with the calibration tube 601. A second piston 6021 is provided at the upper end of the calibration tube 601. The second piston 6021 is located inside the pipe. A spring 6022 is also sleeved below the second piston 6021 in the calibration tube 601. The upper end of the core column 602 passes through the second piston 6021 and is fixedly connected to the calibration mounting part 603.

[0046] The quality control calibration liquid tray 7 is located inside the chassis, inside the reagent storage module 3. A recessed cavity is provided on one side of the quality control calibration liquid tray 7 for placement; when in use, the quality control calibration module 6 is placed in the recessed cavity and kept upright.

[0047] The quality control calibration module 6 is also a component that can be magnetically attracted and disassembled. Its function is to dip into the hydrophobic liquid used for calibration in the quality control calibration liquid tray 7, which is usually paraffin wax.

[0048] The hydrophobic liquid can be paraffin, and the corresponding calibration tube 601 needs to be equipped with a heating wire with heating function. Other hydrophobic materials can also be used, such as the pen ink commonly used in immunohistochemistry pens. Common pen inks include resins, ketones, esters, etc., in which case no additional heating wire is required.

[0049] The upper end of the core column 602 is fixedly connected to the pipe opening of the calibration mounting part 603, and their positions are relatively fixed. When the second piston 6021 is attracted by the negative pressure suction tube 2012, it causes the calibration tube 601 to move upward and the lower end of the core column 602 to extend out of the lower end of the calibration tube 601. This can scrape off excess hydrophobic liquid inside the calibration tube 601 and make it adhere to a ring edge of the calibration tube 601. When pressed on the surface of the glass slide, a hollow ring calibration area can be formed. In addition, the spring 6022 can also play a buffering role during the pressing contact process to prevent the calibration tube 601 from damaging the surface of the glass slide.

[0050] Preferably, the connecting part 2022 has a liquid storage chamber 2024 inside, and the liquid storage chamber 2024 has a first piston 2025 that blocks the two ends of the liquid storage chamber 2024. One end of the liquid storage chamber 2024 is connected to the needle tip 2021, and the other end of the liquid storage chamber 2024 is detachably connected to the negative pressure pipette 2012. The volume of the liquid storage chamber 2024 can be set according to different needs. The liquid storage chamber 2024 in the sample dispensing needle assembly 202 provides additional space for aspirating reagents, which can reduce the length of the needle tip 2021 to a certain extent and compress the overall height of the device. At the same time, in the prior art, the length of the sample dispensing needle cannot be standardized for instruments of different experimental modes such as immunohistochemistry, quality control, and FIFO, because they are adapted to different liquid dispensing volume requirements. The liquid storage chamber 2024 provides additional space for aspirating reagents, which can make the length of the needle tip 2021 uniform, which not only facilitates its storage in the device, but also simplifies the positioning program design of the sample dispensing robotic arm 201, because it simplifies the adjustment on the height coordinate. In addition, the first piston 2025 prevents reagents from flowing back into the negative pressure pipette 2012 and causing contamination.

[0051] Preferably, the top of the connecting part 2022 is threadedly connected to a threaded sleeve 2026, and a sealing ring 2027 is embedded between the threaded sleeve 2026 and the connecting part 2022. When the negative pressure suction tube 2012 is inserted into the connecting part 2022, the side of the sealing ring 2027 is exposed and closely attached to the outer wall of the negative pressure suction tube 2012; the top surface of the first iron sheet 2023 is provided with several anti-slip stripes; the sample needle storage module 4 is provided with a rotating fixture.

[0052] The sealing ring 2027 seals the space between the negative pressure suction tube 2012 and the connecting part 2022, maintaining a stable negative pressure. This allows the replaceable sample needle assembly 202 to stably draw up trace amounts of liquid. The threaded sleeve 2026 can rotate relative to the connecting part 2022. This relative rotation further compresses the sealing ring 2027, thereby secondary tightening of the connection and sealing effect between the negative pressure suction tube 2012 and the connecting part 2022. When it is necessary to replace the sample needle assembly 202, simply release the attraction of the electromagnet suction head 2011 to the first iron plate 2023, thus achieving a quick disassembly solution that balances stable connection and sealing performance.

[0053] The sample dispensing needle storage module 4 includes a rotating fixture. When the electromagnet suction head 2011 at the end of the sample dispensing robotic arm 201 and the sample dispensing needle assembly 202 are engaged and installed, the sample dispensing needle assembly 202 is placed on the rotating fixture. The rotating fixture is used to rotate the connecting part 2022 to achieve the above-mentioned secondary fastening of the negative pressure suction tube 2012 and the connecting part 2022 when the electromagnet suction head 2011 at the end of the sample dispensing robotic arm 201 and the sample dispensing needle assembly 202 are engaged and installed.

[0054] Preferably, each reaction module 1 includes a glass slide tray, a tray loading track 12, a heating base 13, a pressing mechanism, a glass slide 5, and a liquid cover film 103.

[0055] The slide tray includes a long strip main tray and a long strip slide holder 11. The slide holder 11 is slidably connected to the main tray, so that the slide holder 11 can slide out to one side perpendicular to the length of the main tray. The slide holder 11 is used to place the slide 5. The liquid cover film 103 is detachably rotatably connected to the main tray.

[0056] The clamping mechanism is mounted above the heating base 13 in a height-adjustable manner, and the pallet loading track 12 is mounted below the clamping mechanism. The bottom of the main pallet and the pallet loading track 12 are detachably and slidably connected, so that the main pallet can slide between the connecting pallet loading track 12 and the clamping mechanism.

[0057] The pressing mechanism is used to press down the liquid cover film 103 to make it fit against the glass slide 5.

[0058] Each reaction module 1 is equipped with an ejection mechanism, which is used to drive the slide holder 11 to slide out or retract the main tray.

[0059] The main tray includes a first frame 101 and a second frame 102.

[0060] The second frame 102 is set inside the first frame 101 and has rotating shafts 1021 at both ends that are rotatably connected to the first frame 101; the slide holder 11 is provided with positioning grooves for arranging and placing the slides 5, the bottom of the slide holder 11 is slidably connected to the second frame 102, and the second frame 102 is provided with a buckle 104 on the other side away from the sliding direction of the slide holder 11, and the buckle 104 corresponds one-to-one with the liquid cover film 103.

[0061] The bottom of the first frame 101 is slidably connected to the tray loading track 12. The first frame 101 includes a first limiting beam 1011 and a second limiting beam 1012 located on both sides of the rotating shaft 1021 and extending along the direction of the tray loading track 12. The first limiting beam 1011 is located on the side of the slide holder 11 sliding out, and is used to limit the slide holder 11 to be placed horizontally when the second frame 102 rotates to this side at the maximum angle. The second limiting beam 1012 is located on the side away from the slide holder 11 sliding out, and is used to limit the maximum tilt angle of the slide holder 11 when the second frame 102 rotates to this side.

[0062] The liquid cover film 103 is provided with a handle end with a rotating shaft structure. The buckle 104 is used to rotatably connect the handle end of the liquid cover film 103, so that the liquid cover film 103 covers the glass slide 5 one by one and the liquid cover film 103 can be flipped upward relative to the second frame 102.

[0063] The slide holder 11 is provided with guide protrusions 111 on both sides corresponding to each liquid cover film 103. The guide protrusions 111 are used to lift the liquid cover film 103 when the slide holder 11 slides out.

[0064] The slides in the slide tray are placed on a slide holder that can slide out. During the quality control sample addition operation, they will not be interfered with by the liquid cover film. At this time, the slides are in a horizontal position. When the slide holder is put back into the main tray, the liquid cover film is repeatedly placed on top of the slides. With the help of the clamping mechanism, the liquid cover film and the slides are tilted at a certain angle at the same time, which facilitates the formation of liquid film by using the siphon principle.

[0065] The reaction module 1 is equipped with a light shield 8 on one side, and the light shield 8 has openings on one or both sides to accommodate the reaction module 1. The light shield 8 is connected to the inside of the chassis via an electrically controlled slide rail mechanism, which is used to drive the light shield 8 to block the reaction module 1. The light shield 8 is used to provide a light-protected environment by covering the reaction module 1 during the FISH process. The design of the light shield 8 with openings on both sides can accommodate the reaction modules 1 on both sides respectively, simplifying the equipment structure.

[0066] The reaction module and light shield 8 provide three different application modes. The first mode involves the slide holder 11 extending between the light shield 8 and the liquid cover film 103, allowing the slides to unfold for FISH sample loading. Then, an electrically controlled sliding mechanism drives the light shield 8 to move towards one side of the reaction module 1 and cover it, creating the third mode: FISH incubation. The third mode involves the slide holder 11 being retrieved after sample loading and entering the immunohistochemical staining incubation mode.

[0067] Preferably, the guide protrusion 111 is lower on one side of the slide holder 11 in the sliding direction than on the other side, so that its upper edge forms a bevel structure. The liquid cover film 103 has limiting protrusions 106 on both sides of its end, and the limiting protrusions 106 overlap the upper edge of the guide protrusion 111.

[0068] Preferably, the pressing mechanism includes a cover 141 disposed on the upper part and a spring pressure head 142 disposed on the lower surface of the cover 141. The spring pressure head 142 is located on the side of the second frame 102 away from the slide holder 11. The pressing mechanism presses down to make the spring pressure head 142 push the second frame 102 downward to rotate to the maximum limit angle away from the slide holder 11.

[0069] Preferably, the clamping mechanism is provided with a set of cam mechanisms 16 at both ends, and the cam mechanisms 16 are used to drive the clamping mechanism to rise and fall.

[0070] Preferably, the ejection mechanism includes an ejection frame 153 and a pair of electromagnetic push rods 15. The ejection frame 153 is disposed below the heating base 13 of each reaction module 1 and is slidably connected to the heating base 13. The electromagnetic push rods 15 are located below the heating base 13 and are connected to the ejection frame 153. A detachable connection structure is provided between the end of the ejection frame 153 and the slide holder 11. The electromagnetic push rods 15 are used to eject and retract the slide holder 11 through the ejection frame 153.

[0071] Preferably, the detachable connection structure includes a first hook 151 and a second hook 152. The first hook 151 is provided on both sides of the end of the push-out frame 153. The end of the first hook 151 is a barbed structure that bends toward the slide holder 11 in the sliding direction and opens downward. The first hook 151 located at the inner end in the main tray insertion direction is further away from the main tray than the first hook 151 at the other end. The second hook 152 is provided below the slide holder 11 in the sliding direction. The end of the second hook 152 is a hook-shaped structure that bends toward the inner end in the main tray insertion direction and latches 104. The second hook 152 located at the inner end in the main tray insertion direction is further away from the main tray than the second hook 152 at the other end.

[0072] The technical solution of this invention integrates a series of automated operations from quality control to staining in immunohistochemistry experiments, as well as fluorescence in situ hybridization, into one device, thereby improving the level of laboratory automation and reducing the laboratory footprint.

Claims

1. A quality-controlled immunohistochemistry and fluorescence in situ hybridization staining integrated machine, characterized in that, The reaction module (1), the sample adding module (2), the reagent storage module (3), the sample adding needle storage module (4), the sample adding needle discarding module (9), the quality control calibration module (6) and the quality control calibration liquid tray (7) are arranged in the cabinet. The sample adding mechanical arm (201) is provided with an electromagnet suction head (2011), a negative pressure suction pipe (2012) and a negative pressure pump (2013) connected with the negative pressure suction pipe (2012) at the end, the electromagnet suction head (2011) is arranged on one side of the negative pressure suction pipe (2012), the sample adding needle assembly (202) comprises a needle head (2021) and a connecting part (2022), the connecting part (2022) is used for being connected with the negative pressure suction pipe (2012), and the connecting part (2022) is further provided with a first iron sheet (2023) used for adsorbing the electromagnet suction head (2011). The sample adding needle storage module (4) is used for storing the replaceable sample adding needle assembly (202), and the sample adding needle discarding module (9) is used for storing the discarded replaceable sample adding needle assembly (202). The quality control calibration module (6) comprises a hollow calibration pipe (601), a core column (602) movably sleeved in the calibration pipe (601) and a calibration mounting part (603), the calibration mounting part (603) is provided with a second iron sheet (6031) used for adsorbing the electromagnet suction head (2011), the calibration mounting part (603) is provided with a pipeline communicating with the calibration pipe (601), an upper end of the calibration pipe (601) is provided with a second piston (6021), the second piston (6021) is located in the pipeline, the calibration pipe (601) is further sleeved with a spring (6022) below the second piston (6021), and the core column (602) passes through the second piston (6021) at the upper end and is fixedly connected with the calibration mounting part (603).

2. The integrated machine for immunohistochemistry and fluorescence in situ hybridization staining with quality control according to claim 1, characterized in that, The connecting part (2022) is internally provided with a liquid storage cavity (2024), the liquid storage cavity (2024) is internally provided with a first piston (2025) blocking two ends of the liquid storage cavity (2024), one end of the liquid storage cavity (2024) communicates with the needle head (2021), and the other end of the liquid storage cavity (2024) is detachably connected with the negative pressure suction pipe (2012).

3. The integrated machine for immunohistochemistry and fluorescence in situ hybridization staining with quality control according to claim 1, characterized in that, The connecting part (2022) is threadedly connected with a threaded sleeve (2026) at the top, a sealing ring (2027) is embedded between the threaded sleeve (2026) and the connecting part (2022), when the negative pressure suction pipe (2012) is inserted into the connecting part (2022), the sealing ring (2027) exposes the side surface and tightly abuts the outer side wall of the negative pressure suction pipe (2012), the top surface of the first iron sheet (2023) is provided with a plurality of anti-skid stripes, and the sample adding needle storage module (4) is provided with a rotating tool (401).

4. The immunohistochemical and fluorescence in situ hybridization staining integrated machine with quality control according to claim 1, characterized in that, The reaction module (1) includes a slide tray, a tray loading track (12), a heating base (13), a pressing mechanism, a slide (5), and a liquid cover film cover (103) The slide tray includes a long strip-shaped main tray and a long strip-shaped slide rack (11), the slide rack (11) and the main tray are slidingly connected, the slide rack (11) can slide out to one side of the length direction of the main tray, the slide rack (11) is used for placing the slide (5), and the liquid cover film cover (103) is detachably and rotationally connected to the main tray The pressing mechanism is installed above the heating base (13), the tray loading track (12) is installed below the pressing mechanism, the bottom of the main tray is detachably and slidingly connected to the tray loading track (12), and the main tray can slide into the connection between the tray loading track (12) and the pressing mechanism The pressing mechanism is used for pressing the liquid cover film cover (103) to make the liquid cover film cover (103) adhere to the slide (5) Each reaction module (1) is provided with a set of ejection mechanism, and the ejection mechanism is used for driving the slide rack (11) to slide out or retract into the main tray The main tray includes a first frame (101) and a second frame (102) The second frame (102) is arranged in the first frame (101) and rotationally connected to the first frame (101) through rotation shafts (1021) arranged at two ends of the second frame (102), the slide rack (11) is provided with positioning grooves for arranging and placing the slides (5), the bottom of the slide rack (11) is slidingly connected to the second frame (102), the second frame (102) is provided with buckles (104) on the side away from the slide-out direction of the slide rack (11), and the buckles (104) correspond to the liquid cover film covers (103) one by one The bottom of the first frame (101) is slidingly connected to the tray loading track (12), the first frame (101) includes first limiting beams (1011) and second limiting beams (1012) extending along the direction of the tray loading track (12) and located on the two sides of the rotation shafts (1021), the first limiting beams (1011) are located on the side of the slide-out direction of the slide rack (11) and used for limiting the slide rack (11) to be horizontally placed when the second frame (102) is rotated to the maximum angle on this side, and the second limiting beams (1012) are located on the side away from the slide-out direction of the slide rack (11) and used for limiting the maximum inclination angle of the slide rack (11) when the second frame (102) is rotated on this side The liquid cover film cover (103) is provided with a handle end with a rotation shaft structure, the buckles (104) are used for rotationally connecting the handle end of the liquid cover film cover (103), the liquid cover film cover (103) covers the slide (5) one by one, and the liquid cover film cover (103) can be flipped upward relative to the second frame (102) The slide rack (11) is provided with guide protrusions (111) on the two sides corresponding to each liquid cover film cover (103), and the guide protrusions (111) are used for lifting the liquid cover film cover (103) when the slide rack (11) slides out.

5. The immunohistochemical and fluorescence in situ hybridization staining integrated machine with quality control according to claim 4, characterized in that, The reaction module (1) is provided with a light shield (8) on one side, and the light shield (8) is provided with an opening for accommodating the reaction module (1) on one side or both sides; the light shield (8) is connected to the inside of the cabinet through an electric control sliding rail mechanism, and the electric control sliding rail mechanism is used for driving the light shield (8) to shield the reaction module (1).

6. The integrated machine for immunohistochemistry and fluorescence in situ hybridization staining with quality control according to claim 4, characterized in that, The height of the guide protrusion (111) on one side in the slide-out direction of the slide rack (11) is lower than that on the other side, so that the upper edge thereof forms a slope structure, and the ends of the liquid cover film cover sheet (103) are provided with limiting protrusions (106), which are overlapped on the upper edge of the guide protrusion (111).

7. The IHC and FISH staining integrated machine with quality control according to claim 4, wherein, The pressing mechanism includes a cover (141) arranged above and a spring pressing head (142) arranged on the lower surface of the cover (141), the spring pressing head (142) is located on the side of the rotation shaft (1021) of the second frame (102) away from the slide-out direction of the slide rack (11), and the pressing mechanism is pressed downward to make the spring pressing head (142) push the second frame (102) to rotate to the maximum limit angle away from the slide-out direction of the slide rack (11).

8. The IHC and FISH staining integrated machine with quality control according to claim 7, characterized in that, Both ends of the pressing mechanism are provided with a set of cam mechanisms (16), which are used for driving the pressing mechanism to lift and lower.

9. The IHC and FISH staining integrated machine with quality control according to claim 4, wherein, The ejection mechanism includes a push-out frame (153) and a pair of electromagnetic push rods (15), the push-out frame (153) is arranged below the heating base (13) of each reaction module (1) and is in sliding connection with the heating base (13), the electromagnetic push rod (15) is located below the heating base (13) and is connected with the push-out frame (153), and a detachable connection structure is arranged between the end of the push-out frame (153) and the slide rack (11), and the electromagnetic push rod (15) is used for pushing out and retracting the slide rack (11) through the push-out frame (153).

10. The integrated machine for immunohistochemistry and fluorescence in situ hybridization staining with quality control according to claim 9, characterized in that, The detachable connection structure includes a first clamping hook (151) and a second clamping hook (152), the end of the push-out frame (153) is provided with the first clamping hook (151) on both sides upward, the end of the first clamping hook (151) is a barb-shaped structure curved to the side of the slide-out direction of the slide rack (11) and opening downward, and the first clamping hook (151) located at the inner end of the main tray insertion direction is farther away from the main tray than the other end; the lower side of the slide-out direction of the slide rack (11) is provided with the second clamping hook (152), the end of the second clamping hook (152) is a clamping hook-shaped structure curved to the clamping buckle (104) at the inner end of the main tray insertion direction, and the second clamping hook (152) located at the inner end of the main tray insertion direction is farther away from the main tray than the other end.

Citation Information

Patent Citations

  • Automatic chemistry analyzer

    CA2501895A1

  • Immunohistochemical quality control and dyeing all-in-one machine

    CN119086954A