Immunohistochemical and fluorescence in-situ hybridization dyeing all-in-one machine with quality control

Abstract

The invention discloses an immunohistochemical and fluorescence in-situ hybridization dyeing all-in-one machine with quality control. The all-in-one machine comprises 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 which are arranged in a case. A series of automatic operations of immunohistochemical experiments from quality control to dyeing treatment and fluorescence in-situ hybridization are integrated in one device, so that the automation degree of a laboratory is improved, and the occupied space of the laboratory is reduced.

Description

Technical Field

[0001] The present invention relates to the field of experimental instruments, and in particular to an instrument with integrated immunohistochemical quality control, automated staining processing and fluorescence in situ hybridization functions. Background Art

[0002] Immunohistochemistry is a technique that uses the basic principle of immunology - antigen-antibody reaction, that is, the principle of specific binding between antigen and antibody, to determine the antigenic peptides and proteins in tissue cells through chemical reactions to make the color developing agents such as fluorescein, enzymes, metal ions, and isotopes of labeled antibodies develop color, and to conduct localization, qualitative and relative quantitative research on them. Immunohistochemistry quality control instruments and immunohistochemistry staining instruments are fully automatic instruments for immunohistochemistry technology.

[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 samples to detect and locate specific DNA or RNA sequences. The most important factors in FISH are temperature, light, humidity, and the pH value of various reagents. Temperature and humidity directly affect the hybridization efficiency of the probe and the target DNA; light affects the intensity of the fluorescent dye, so the probe should be kept away from light, and the hybridized slides can be sealed with anti-fluorescence quenching agents and kept away from light; the pH of various reagents must also meet the requirements accurately, which is also directly related to the stability of FISH.

[0004] The existing immunohistochemistry quality control instruments and immunohistochemistry staining instruments are separate devices, lacking an instrument that organically integrates the two. This results in high equipment procurement costs, large space occupied, and additional sample transfer operations, affecting work efficiency. Summary of the invention

[0005] The present invention aims to overcome the above-mentioned deficiencies of the instruments and equipment in the prior art and provides an immunohistochemistry and fluorescent in situ hybridization staining all-in-one machine with quality control.

[0006] To achieve the above object, the present invention adopts the following technical solutions:

[0007] The present application discloses an integrated immunohistochemistry and fluorescent in situ hybridization staining machine with quality control, 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 chassis;

[0008] The sample loading module comprises a sample loading mechanical arm and a replaceable sample loading needle assembly, wherein the end of the sample loading mechanical arm is provided with an electromagnet suction head, a negative pressure suction pipe and a negative pressure pump connected to the negative pressure suction pipe, the negative pressure pump is connected to the negative pressure suction pipe, the electromagnet suction head is arranged on one side of the negative pressure suction pipe, the sample loading needle assembly comprises a needle head and a connecting part, the connecting part is used to be connected to the negative pressure suction pipe, and the connecting part is also provided with a first iron sheet for adsorption of the electromagnet suction head;

[0009] 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;

[0010] The quality control calibration module includes a hollow calibration tube, a core column movably mounted inside the calibration tube, and a calibration mounting part. The calibration mounting part is provided with a second iron sheet for adsorption by the electromagnet suction head. The calibration mounting part is provided with a pipeline connected to the calibration tube. A piston is provided at the upper end of the calibration tube. The piston is located in the pipeline. The calibration tube is also provided with a spring under the piston. The upper end of the core column passes through the piston and is fixedly connected to the calibration mounting part.

[0011] Preferably, a liquid storage cavity is provided inside the connecting portion, and a piston is provided in the liquid storage cavity to block the two ends of the liquid storage cavity. One end of the liquid storage cavity is connected to the needle head, and the other end of the liquid storage cavity is detachably connected to the negative pressure suction tube.

[0012] Preferably, a threaded sleeve is threadedly connected to the top of the connecting part, and a sealing ring is embedded between the threaded sleeve and the connecting part. When the negative pressure straw is inserted into the connecting part, the side of the sealing ring is exposed and tightly attached to the outer wall of the negative pressure straw; a plurality of anti-slip stripes are provided on the top surface of the first iron sheet; and the sample needle storage module is provided with a rotating tooling.

[0013] Preferably, the reaction module comprises a slide tray, a tray loading track, a heating base, a clamping mechanism, a slide, a liquid cover film cover

[0014] The slide tray comprises a long main tray and a long slide rack, the slide rack and the main tray are slidably connected, so that the slide rack can slide out to one side perpendicular to the length of the main tray, the slide rack is used to place the slide, and the liquid cover film cover is detachably connected to the main tray by rotation;

[0015] The clamping mechanism is installed above the heating base in a liftable manner, the tray loading track is installed below the clamping mechanism, and the bottom of the main tray and the tray loading track are detachably connected to each other in a sliding manner, so that the main tray can slide into the connection between the tray loading track and the clamping mechanism;

[0016] The pressing mechanism is used to press down the liquid cover film cover sheet to make it fit with the glass slide;

[0017] Each reaction module is equipped with a set of ejection mechanisms, and the ejection mechanisms are used to drive the slide rack to slide out or retract the main tray;

[0018] The main tray includes a first frame and a second frame;

[0019] The second frame structure is arranged in the first frame and has rotating shafts at both ends thereof and is rotatably connected to the first frame; the slide rack is provided with positioning grooves for arranging and placing slides, the bottom of the slide rack is slidably connected to the second frame, and the second frame is provided with a buckle on the other side away from the sliding direction of the slide rack, and the buckle corresponds to the liquid cover film cover one by one;

[0020] The bottom of the first frame is slidably connected to the tray loading track, and 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, wherein the first limiting beam is located on the side of the slide rack sliding out direction, and is used to limit the slide rack to be placed horizontally when the second frame rotates to the side at the maximum angle, and the second limiting beam is located on the side away from the slide rack sliding out direction, and is used to limit the maximum inclination angle of the slide rack when the second frame rotates to the side;

[0021] The liquid cover film cover sheet is provided with a handle end with a rotating shaft structure, and the buckle is used to rotate the handle end connected to the liquid cover film cover sheet so that the liquid cover film cover sheets are covered on the glass slide one by one and the liquid cover film cover sheet can be turned upward relative to the second frame;

[0022] The slide rack is provided with guide protrusions on both sides corresponding to each liquid cover film cover sheet, and the guide protrusions are used to lift the liquid cover film cover sheet when the slide rack slides out.

[0023] 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 side or both sides of the light shield; the light shield is connected to the inside of the chassis through an electric control slide mechanism, and the electric control slide mechanism is used to drive the light shield to shield the reaction module.

[0024] Preferably, the guide protrusion is lower on one side than the other side in the sliding direction of the glass slide rack so that its upper edge forms a slope structure, and limiting protrusions are provided on both sides of the end of the liquid cover film cover, and the limiting protrusions overlap the upper edge of the guide protrusion.

[0025] Preferably, the clamping mechanism includes a cover body arranged at the top and a spring pressure head arranged on the lower surface of the cover body, and the spring pressure head is located on the side of the rotating shaft of the second frame away from the sliding out glass slide rack. The clamping mechanism presses down to cause the spring pressure head to push the second frame downward to rotate to the maximum limit angle on the side away from the sliding out glass slide rack.

[0026] Preferably, a set of cam mechanisms are provided at both ends of the clamping mechanism, and the cam mechanisms are used to drive the clamping mechanism to rise and fall.

[0027] Preferably, the ejection mechanism includes an ejection frame and a pair of electromagnetic push rods, the ejection frame is arranged below the heating base of each reaction module and is slidably connected to the heating base, the electromagnetic push rod is located below the heating base and connected to the ejection frame, a detachable connecting structure is provided between the end of the ejection frame and the glass slide rack, and the electromagnetic push rod is used to push out and retract the glass slide rack through the ejection frame.

[0028] Preferably, the detachable connection structure includes a first hook and a second hook, the first hooks are provided upward on both sides of the end of the push-out frame, the end of the first hook is a hook-shaped structure that is bent toward one side of the sliding out direction of the glass slide rack and opens downward, and the first hook located at the inner end in the insertion direction of the main tray is farther away from the main tray than the first hook at the other end; a second hook is provided below one side of the sliding out direction of the glass slide rack, the end of the second hook is a hook-shaped structure that is bent and buckled toward the inner end in the insertion direction of the main tray, and the second hook located at the inner end in the insertion direction of the main tray is farther away from the main tray than the second hook at the other end.

[0029] Therefore, the present invention has the following beneficial effects:

[0030] (1) A series of automated operations from quality control to staining processing of immunohistochemistry experiments and fluorescence in situ hybridization are integrated into one device, which improves the degree of laboratory automation and reduces the laboratory space occupied.

[0031] (2) The slides in the slide tray are placed on a slide rack that can slide out. During the quality control sample addition operation, the slides will not be disturbed by the liquid cover film, and the slides are in a horizontal state at this time. When the slide rack is put into the main tray, the liquid cover film repeatedly covers the top of the slide, and cooperates with the clamping mechanism to make the liquid cover film and the slide tilt at a certain angle at the same time, so as to facilitate the formation of the liquid film by the siphon principle.

[0032] (3) The end of the sample loading robot arm and the replaceable sample loading needle assembly are automatically connected and disassembled; in this way, the sample loading needle assembly can be directly replaced when switching to different experimental modes to prevent contamination; the liquid storage chamber 2024 provides an additional space for absorbing reagents, so that the length of the needle head 2021 can be unified, which is not only convenient for its storage in the device, but also simplifies the positioning program design of the sample loading robot arm 201, because it simplifies the debugging on the height coordinate. In addition, the piston 2024 blocks the reagent from flowing back to the negative pressure pipette 2012 and causing contamination.

[0033] (4) The quality control calibration module is also a component that can be adsorbed and removed by magnetic force. Its function is to dip the hydrophobic liquid used for calibration in the quality control calibration liquid tray 7, usually paraffin, and then press it on the surface of the glass slide to form a hollow circular calibration area. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 It is a structural diagram of the immunohistochemistry and fluorescent in situ hybridization staining all-in-one machine with quality control of the present invention.

[0035] Figure 2 It is a structural diagram of the sample loading robot arm 201 and the replaceable sample loading needle assembly 202.

[0036] Figure 3 It is a structural diagram of the sample loading robot 201 and the quality control calibration module 6.

[0037] Figure 4 Schematic diagram of the immunohistochemical staining working status of the reaction module.

[0038] Figure 5 This is a schematic diagram of the structure of the reaction module during the quality control sample addition process.

[0039] Figure 6 Schematic diagram of the exploded structure of the main tray and slide rack.

[0040] Figure 7 This is a cross-sectional view of the reaction module during immunohistochemical staining.

[0041] Figure 8 This is a cross-sectional view of the reaction module during the quality control sample addition process. DETAILED DESCRIPTION

[0042] The present invention is further described below in conjunction with the accompanying drawings and specific embodiments.

[0043] like Figure 1 As shown, the present application is an all-in-one immunohistochemistry and fluorescent in situ hybridization staining machine with quality control, which is characterized in that it includes a plurality of reaction modules 1, a sample adding module 2, a reagent storage module 3, a sample adding needle storage module 4, a sample adding needle discard module 5, a quality control calibration module 6, a quality control calibration liquid tray 7, and a movable light shielding cover 8 arranged in a chassis.

[0044] The sample loading module 2 includes a sample loading robot arm 201 and a replaceable sample loading needle assembly 202. The end of the sample loading robot arm 201 is provided with an electromagnet suction head 2011, a negative pressure pipette 2012 and a negative pressure pump 2013 connected to the negative pressure pipette. The negative pressure pump 2013 is connected to the negative pressure pipette 2012. The electromagnet suction head 2011 is arranged on one side of the negative pressure pipette 2012. The sample loading needle assembly 202 includes a needle head 2021 and a connecting part 2022. The connecting part 2022 is used to be connected to the negative pressure pipette 2022. The connecting part 2022 is also provided with a first iron sheet 2023 for adsorbing the electromagnet suction head 2011. The electromagnet suction head 2011 and the first iron sheet 2023 realize controllable magnetic adsorption, so that the end of the sample loading robot 201 and the replaceable sample loading needle assembly 202 can be automatically connected and disassembled; in this way, when switching to different experimental modes, the sample loading needle assembly 202 can be directly replaced to prevent contamination; the sample loading robot 201 can place the replaced sample loading needle assembly 202 into the sample loading needle disposal module 5 for recycling and unified cleaning.

[0045] The sample needle storage module 4 is used to store the replaceable sample needle assembly 202, and the sample needle disposal module 5 is used to store the discarded replaceable sample needle assembly 202; after the experiment, the sample needles in the sample needle disposal module 5 can be taken out, cleaned, and then put back into the sample needle storage module 4 for next use.

[0046] The quality control calibration module 6 includes a hollow calibration tube 601, a core column 602 movably mounted inside the calibration tube 601, and a calibration mounting portion 603. The calibration mounting portion 603 is provided with a second iron sheet 6031 for adsorption by the electromagnet suction head 2011. The calibration mounting portion 603 is provided with a pipeline connected to the calibration tube 601. A piston 6021 is provided at the upper end of the calibration tube 601. The piston 6021 is located in the pipeline. The calibration tube 601 is also provided with a spring 6022 under the piston 6021. The upper end of the core column 602 passes through the piston 6021 and is fixedly connected to the calibration mounting portion 603.

[0047] The quality control calibration liquid tray 7 is arranged in the chassis, and is located inside the reagent storage module 3. A concave cavity for placement is arranged on one side of the quality control calibration liquid tray 7; the quality control calibration module 6 is placed in the concave cavity when in standby, and maintains an upright posture.

[0048] The quality control calibration module 6 is also a component that can be adsorbed and disassembled by magnetic force. Its function is to dip the hydrophobic liquid used for calibration in the quality control calibration liquid tray 7, and paraffin is commonly used.

[0049] The hydrophobic liquid can be paraffin, and the corresponding calibration tube 601 needs to be provided with a heating wire with a heating function. Other hydrophobic substances can also be used, such as the pen liquid commonly used in immunohistochemistry pens, which include gums, ketones, esters, etc., and no additional heating wire is required.

[0050] The upper end of the core column 602 is fixedly connected to the pipe mouth of the calibration mounting part 603 and its position is relatively fixed. When the piston 6021 is adsorbed by the negative pressure suction tube 2012, the calibration tube 601 moves upward and the lower end of the core column 602 extends relatively out of the lower pipe mouth of the calibration tube 601, thereby scraping off excess hydrophobic liquid on the inside of the calibration tube 601 and making it adhere to a circle of the edge of the calibration tube 601. In this way, when it is pressed on the surface of the glass slide, a hollow circular calibration area can be formed, and 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.

[0051] Preferably, a liquid storage chamber 2024 is provided inside the connecting portion 2022, and a piston 2025 is provided inside the liquid storage chamber 2024 to block the two ends of the liquid storage chamber 2024. One end of the liquid storage chamber 2024 is connected to the needle head 2021, and the other end of the liquid storage chamber 2024 is detachably connected to the negative pressure suction pipe 2012. The volume of the liquid storage chamber 2024 can be set according to different needs. The liquid storage chamber 2024 in the sample addition needle assembly 202 provides an additional space for absorbing reagents, which can reduce the length of the needle head 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 addition needle cannot be unified for instruments with different experimental modes such as immunohistochemistry, quality control, and fish because they adapt to different liquid addition requirements. The liquid storage chamber 2024 provides an additional space for absorbing reagents, which can make the length of the needle head 2021 uniform, which is not only convenient for its storage in the device, but also simplifies the positioning program design of the sample addition mechanical arm 201, because it simplifies the debugging on the height coordinate. In addition, the piston 2024 blocks the reagent from flowing back into the negative pressure pipette 2012 and causing contamination.

[0052] Preferably, a threaded sleeve 2026 is threadedly connected to the top of the connecting portion 2022, and a sealing ring 2027 is embedded between the threaded sleeve 2026 and the connecting portion 2022. When the negative pressure straw 2012 is inserted into the connecting portion 2022, the side of the sealing ring 2027 is exposed and tightly attached to the outer wall of the negative pressure straw 2012; a plurality of anti-slip stripes are provided on the top surface of the first iron sheet 2023; and the sample adding needle storage module 4 is provided with a rotating tooling.

[0053] The sealing ring 2027 seals the space between the negative pressure pipette 2012 and the connecting part 2022, maintains a stable negative pressure, and enables the replaceable sample needle assembly 202 to stably absorb a trace amount of liquid. The threaded sleeve 2026 can rotate relative to the connecting part 2022, and the sealing ring 2027 can be further compressed by relative rotation, thereby secondary tightening the connection and sealing effect between the negative pressure pipette 2012 and the connecting part 2022. When the sample needle assembly 202 needs to be replaced, the electromagnetic suction head 2011 only needs to release the attraction to the first iron sheet 2023, thereby realizing a quick disassembly solution that takes into account both stable connection and sealing performance.

[0054] The sample needle storage module 4 includes a rotating fixture. When the electromagnet suction head 2011 at the end of the sample adding mechanical arm 201 and the sample adding needle assembly 202 are engaged and installed, the sample adding needle assembly 202 is placed on the rotating fixture. The rotating fixture is used to rotate the connecting part 2022 to realize the above-mentioned secondary tightening operation of the negative pressure pipette 2012 and the connecting part 2022 when the electromagnet suction head 2011 at the end of the sample adding mechanical arm 201 and the sample adding needle assembly 202 are engaged and installed.

[0055] Preferably, the reaction module 1 includes a glass slide tray, a tray loading track 12 , a heating base 13 , a clamping mechanism, a glass slide 5 , and a liquid cover film cover 103 .

[0056] The slide tray includes a long main tray and a long slide rack 11. The slide rack 11 is slidably connected to the main tray so that the slide rack 11 can slide out to one side perpendicular to the length of the main tray. The slide rack 11 is used to place the slide 5, and the liquid cover film cover 103 is detachably rotatably connected to the main tray.

[0057] The clamping mechanism is installed above the heating base 13 in a liftable manner, and the pallet loading track 12 is installed below the clamping mechanism. The bottom of the main pallet and the pallet loading track 12 are detachably slidably connected, so that the main pallet can slide into the connection between the pallet loading track 12 and the clamping mechanism.

[0058] The pressing mechanism is used to press down the liquid cover film cover sheet 103 to make it fit with the slide glass 5.

[0059] Each reaction module 1 is equipped with a set of ejection mechanisms, and the ejection mechanisms are used to drive the slide rack 11 to slide out or retract the main tray.

[0060] The main tray includes a first frame 101 and a second frame 102 .

[0061] The second frame 102 structure is arranged in the first frame 101 and has rotating shafts 1013 at both ends to be rotatably connected to the first frame 101; the glass slide rack 11 is provided with positioning grooves for arranging and placing the slides 5, and the bottom of the glass slide rack 11 is slidably connected to the second frame 102. The second frame 102 is provided with a buckle 104 on the other side away from the sliding direction of the glass slide rack 11, and the buckle 104 corresponds to the liquid cover film cover 103 one by one.

[0062] 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 1013 and extending along the direction of the tray loading track 12. The first limiting beam 1011 is located on the side of the sliding-out direction of the glass slide rack 11, and is used to limit the glass slide rack 11 to be horizontally placed 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 sliding-out direction of the glass slide rack 11, and is used to limit the maximum inclination angle of the glass slide rack 11 when the second frame 102 rotates to this side.

[0063] The liquid cover film cover sheet 103 is provided with a handle end with a rotating shaft structure, and the buckle 104 is used to rotate the handle end connected to the liquid cover film cover sheet 103 so that the liquid cover film cover sheet 103 can be covered on the glass slide 5 one by one and the liquid cover film cover sheet 103 can be flipped upward relative to the second frame 102.

[0064] The slide rack 11 is provided with guide protrusions 111 on both sides corresponding to each liquid cover film cover sheet 103 , and the guide protrusions 111 are used to lift the liquid cover film cover sheet 103 when the slide rack 11 slides out.

[0065] The slides in the slide tray are placed on a slide rack that can slide out. During the operation of quality control sample addition, they will not be disturbed by the liquid cover film cover, and the slides are in a horizontal state at this time. When the slide rack is put into the main tray, the liquid cover film cover is repeatedly covered on the top of the slide, and cooperates with the clamping mechanism to make the liquid cover film cover and the slide tilted at a certain angle at the same time, so as to facilitate the formation of the liquid film by the siphon principle.

[0066] A light shield 8 is provided on one side of the reaction module 1, and an opening for accommodating the reaction module 1 is provided on one side or both sides of the light shield 8; the light shield 8 is connected to the inside of the chassis through an electric control slide mechanism, and the electric control slide mechanism is used to drive the light shield 8 to shield the reaction module 1. The light shield 8 is used to cover the reaction module 1 in the FISH process to provide a light-proof environment. The design of the light shield 8 with openings on both sides can take into account the reaction modules 1 on both sides respectively, simplifying the equipment structure.

[0067] The reaction module and the light shield 8 provide three different application modes. The first is that the slide rack 11 is pushed out and positioned between the light shield 8 and the liquid cover film cover 103, the slide is unfolded for FISH loading, and then the electric control slide mechanism drives the light shield 8 to move to one side of the reaction module 1 and covers the reaction module 1, and one side becomes the third mode, i.e., the FISH incubation mode. The third mode is that after loading, the slide rack 11 is recovered and enters the immunohistochemical staining incubation mode.

[0068] Preferably, the height of the guide protrusion 111 on one side in the sliding direction of the glass slide rack 11 is lower than that on the other side so that its upper edge forms a slope structure, and limiting protrusions 106 are provided on both sides of the end of the liquid cover membrane cover 103, and the limiting protrusions 106 overlap the upper edge of the guide protrusion 111.

[0069] Preferably, the clamping mechanism includes a cover body 141 arranged on the top and a spring pressure head 142 arranged on the lower surface of the cover body 141, and the spring pressure head 142 is located on the side of the rotating shaft 1013 of the second frame 102 away from the slide rack 11 that slides out. The clamping mechanism presses down to cause the spring pressure head 142 to push the second frame 102 downward to rotate to the maximum limit angle on the side away from the slide rack 11 that slides out.

[0070] Preferably, a set of cam mechanisms 16 are provided at both ends of the clamping mechanism, and the cam mechanisms 16 are used to drive the clamping mechanism to rise and fall.

[0071] Preferably, the ejection mechanism includes an ejection frame 153 and a pair of electromagnetic push rods 15, the ejection frame 153 is arranged below the heating base 13 of each reaction module 1 and is slidably connected to the heating base 13, the electromagnetic push rod 15 is located below the heating base 13 and is connected to the ejection frame 153, and a detachable connection structure is provided between the end of the ejection frame 153 and the glass slide rack 11, and the electromagnetic push rod 15 is used to push out and retract the glass slide rack 11 through the ejection frame 153.

[0072] Preferably, the detachable connection structure includes a first hook 151 and a second hook 152, and the first hook 151 is provided on both sides of the end of the push-out frame 153, and the end of the first hook 151 is a barbed hook structure that is bent toward one side of the sliding out direction of the glass slide rack 11 and opens downward, and the first hook 151 located at the inner end of the main tray in the insertion direction is farther away from the main tray than the first hook 151 at the other end; a second hook 152 is provided below one side of the sliding out direction of the glass slide rack 11, and the end of the second hook 152 is a hook-shaped structure of the buckle 104 that is bent toward the inner end of the insertion direction of the main tray, and the second hook 152 located at the inner end of the main tray in the insertion direction is farther away from the main tray than the second hook 152 at the other end.

[0073] The technical solution of the present invention integrates a series of automated operations of immunohistochemistry experiments from quality control to staining processing, as well as fluorescence in situ hybridization into one device, thereby improving the degree of laboratory automation and reducing laboratory space occupation.

Claims

1. An all-in-one immunohistochemistry and fluorescence in situ hybridization staining machine with quality control, characterized in that: It comprises a plurality of reaction modules (1), a sample adding module (2), a reagent storage module (3), a sample adding needle storage module (4), a sample adding needle discarding module (5), a quality control calibration module (6), and a quality control calibration liquid tray (7) arranged in a chassis; The sample loading module (2) comprises a sample loading mechanical arm (201) and a replaceable sample loading needle assembly (202); the end of the sample loading mechanical arm (201) is provided with an electromagnet suction head (2011), a negative pressure suction pipe (2012), and a negative pressure pump (2013) connected to the negative pressure suction pipe; the negative pressure pump (2013) is connected to the negative pressure suction pipe (2012); the electromagnet suction head (2011) is arranged on one side of the negative pressure suction pipe (2012); the sample loading needle assembly (202) comprises a needle head (2021) and a connecting part (2022); the connecting part (2022) is used to be connected to the negative pressure suction pipe (2022); the connecting part (2022) is also provided with a first iron sheet (2023) used for adsorption by the electromagnet suction head (2011); The sample needle storage module (4) is used to store the replaceable sample needle assembly (202), and the sample needle disposal module (5) is used to store the discarded replaceable sample needle assembly (202); The quality control calibration module (6) comprises a hollow calibration tube (601), a core column (602) movably mounted inside the calibration tube (601), and a calibration installation part (603). The calibration installation part (603) is provided with a second iron sheet (6031) for adsorption by the electromagnet suction head (2011). The calibration installation part (603) is provided with a pipeline connected to the calibration tube (601). A piston (6021) is provided at the upper end of the calibration tube (601). The piston (6021) is located in the pipeline. The calibration tube (601) is also provided with a spring (6022) below the piston (6021). The upper end of the core column (602) passes through the piston (6021) and is fixedly connected to the calibration installation part (603).

2. The immunohistochemistry and fluorescent in situ hybridization staining machine with quality control according to claim 1 is characterized in that: A liquid storage chamber (2024) is provided inside the connecting portion (2022), and a piston (2025) is provided inside the liquid storage chamber (2024) for blocking the two ends of the liquid storage chamber (2024). One end of the liquid storage chamber (2024) is connected to the needle head (2021), and the other end of the liquid storage chamber (2024) is detachably connected to the negative pressure suction tube (2012).

3. The immunohistochemistry and fluorescence in situ hybridization staining machine with quality control according to claim 1 is characterized in that: The top of the connecting portion (2022) is threadedly connected with a threaded sleeve (2026), and a sealing ring (2027) is embedded between the threaded sleeve (2026) and the connecting portion (2022). When the negative pressure suction tube (2012) is inserted into the connecting portion (2022), the side of the sealing ring (2027) is exposed and closely adheres to the outer wall of the negative pressure suction tube (2012); the top surface of the first iron sheet (2023) is provided with a plurality of anti-slip stripes; and the sample needle storage module (4) is provided with a rotating tool (401).

4. The immunohistochemistry and fluorescent in situ hybridization staining machine with quality control according to claim 1 is characterized in that: The reaction module (1) comprises a glass slide tray, a tray loading track (12), a heating base (13), a pressing mechanism, a glass slide (5), a liquid cover film cover (103) The slide tray comprises a long main tray and a long slide rack (11), the slide rack (11) and the main tray are slidably connected, so that the slide rack (11) can slide out to one side perpendicular to the longitudinal direction of the main tray, the slide rack (11) is used to place the slide (5), and the liquid cover film cover (103) is detachably rotatably connected to the main tray; The clamping mechanism is installed above the heating base (13) in a liftable manner, the tray loading track (12) is installed below the clamping mechanism, and the bottom of the main tray and the tray loading track (12) are detachably connected in a sliding manner, so that the main tray can slide into the connection between the tray loading track (12) and the clamping mechanism; The pressing mechanism is used to press down the liquid cover film cover sheet (103) to make it fit with the glass slide (5); Each reaction module (1) is equipped with a set of ejection mechanisms, and the ejection mechanisms are used to drive the slide rack (11) to slide out or retract the main tray; The main tray comprises a first frame (101) and a second frame (102); The second frame (102) is structurally arranged in the first frame (101) and is provided with rotating shafts (1013) at both ends thereof and is rotatably connected to the first frame (101); the glass slide rack (11) is provided with positioning grooves for arranging and placing glass slides (5); the bottom of the glass slide rack (11) is slidably connected to the second frame (102); the second frame (102) is provided with a buckle (104) on the other side away from the sliding-out direction of the glass slide rack (11); the buckle (104) and the liquid cover film cover (103) correspond one to one; The bottom of the first frame (101) is slidably connected to the tray loading track (12), and the first frame (101) comprises a first limiting beam (1011) and a second limiting beam (1012) located on both sides of the rotating shaft (1013) and extending along the direction of the tray loading track (12), wherein the first limiting beam (1011) is located on the side of the slide rack (11) sliding out, and is used to limit the slide rack (11) to be placed horizontally when the second frame (102) rotates to the side at the maximum angle, and the second limiting beam (1012) is located on the side away from the slide rack (11) sliding out, and is used to limit the maximum inclination angle of the slide rack (11) when the second frame (102) rotates to the side; The liquid cover film cover sheet (103) is provided with a handle end with a rotating shaft structure, and the buckle (104) is used to rotate the handle end connected to the liquid cover film cover sheet (103), so that the liquid cover film cover sheets (103) are covered on the glass slide (5) one by one and the liquid cover film cover sheet (103) can be turned upward relative to the second frame (102); The slide rack (11) is provided with guide protrusions (111) on both sides corresponding to each liquid cover film cover sheet (103), and the guide protrusions (111) are used to lift the liquid cover film cover sheet (103) when the slide rack (11) slides out.

5. The immunohistochemistry and fluorescence in situ hybridization staining machine with quality control according to claim 4 is characterized in that: A light shield (8) is provided on one side of the reaction module (1), and an opening for accommodating the reaction module (1) is provided on one side or both sides of the light shield (8); the light shield (8) is connected to the inside of the chassis via an electric control slide rail mechanism, and the electric control slide rail mechanism is used to drive the light shield (8) to shield the reaction module (1).

6. The immunohistochemistry and fluorescence in situ hybridization staining machine with quality control according to claim 4 is characterized in that: The height of the guide protrusion (111) on one side in the sliding-out direction of the glass slide rack (11) is lower than that on the other side, so that its upper edge forms an inclined surface structure. Limiting protrusions (106) are provided on both sides of the end of the liquid cover film cover sheet (103), and the limiting protrusions (106) overlap the upper edge of the guide protrusion (111).

7. The immunohistochemistry and fluorescent in situ hybridization staining machine with quality control according to claim 4 is characterized in that: The clamping mechanism comprises a cover body (141) arranged at the top and a spring pressure head (142) arranged at the lower surface of the cover body (141); the spring pressure head (142) is located on the side of the rotating shaft (1013) of the second frame (102) away from the side where the glass slide rack (11) slides out; the clamping mechanism presses downward so that the spring pressure head (142) pushes the second frame (102) downward to rotate to a maximum limit angle away from the side where the glass slide rack (11) slides out.

8. The immunohistochemistry and fluorescent in situ hybridization staining machine with quality control according to claim 7 is characterized in that: A set of cam mechanisms (16) are provided at both ends of the clamping mechanism, and the cam mechanisms (16) are used to drive the clamping mechanism to rise and fall.

9. The immunohistochemistry and fluorescent in situ hybridization staining machine with quality control according to claim 4, characterized in that: The ejection mechanism comprises an ejection frame (153) and a pair of electromagnetic push rods (15); the ejection frame (153) is arranged below the heating base (13) of each reaction module (1) and is slidably connected to the heating base (13); the electromagnetic push rod (15) is located below the heating base (13) and is connected to the ejection frame (153); a detachable connection structure is provided between the end of the ejection frame (153) and the glass slide rack (11); the electromagnetic push rod (15) is used to eject and retract the glass slide rack (11) through the ejection frame (153).

10. The immunohistochemistry and fluorescent in situ hybridization staining machine with quality control according to claim 1, characterized in that: The detachable connection structure comprises a first hook (151) and a second hook (152); the first hooks (151) are upwardly arranged on both sides of the end of the push-out frame (153); the ends of the first hooks (151) are inverted hook-shaped structures bent toward one side of the slide rack (11) in the direction of sliding out and opening downward, and the first hook (151) located at the inner end in the insertion direction of the main tray is farther away from the main tray than the first hook (151) at the other end; the second hook (152) is arranged below one side of the slide rack (11) in the direction of sliding out, the ends of the second hooks (152) are inverted hook-shaped structures bent toward the inner end in the direction of inserting the main tray to form a buckle (104), and the second hook (152) located at the inner end in the direction of inserting the main tray is farther away from the main tray than the second hook (152) at the other end.

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