CN111323287A - Full-automatic immunohistochemical dyeing equipment - Google Patents

Full-automatic immunohistochemical dyeing equipment Download PDF

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Publication number
CN111323287A
CN111323287A CN202010217038.XA CN202010217038A CN111323287A CN 111323287 A CN111323287 A CN 111323287A CN 202010217038 A CN202010217038 A CN 202010217038A CN 111323287 A CN111323287 A CN 111323287A
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reagent
incubator
liquid
temperature
needle
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CN111323287B (en
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孟慧娟
戚闻
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Beijing Haigre Biotechnology Co ltd
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Beijing Haigre Biotechnology Co ltd
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00Sampling; Preparing specimens for investigation
    • G01N1/28Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/30Staining; Impregnating ; Fixation; Dehydration; Multistep processes for preparing samples of tissue, cell or nucleic acid material and the like for analysis
    • G01N1/31Apparatus therefor
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00Sampling; Preparing specimens for investigation
    • G01N1/28Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/44Sample treatment involving radiation, e.g. heat
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1009Characterised by arrangements for controlling the aspiration or dispense of liquids

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  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Physics & Mathematics (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)

Abstract

The invention relates to a full-automatic immunohistochemical staining device. The device comprises a body, an injection pump, a double-needle liquid transfer arm, a reagent box, a high-temperature incubator, a liquid path system, a storage box, a desktop host and a reference platform; the desktop host controls the injection pump, the double-needle liquid transfer arm, the liquid path system and the high-temperature incubator through the control circuit board according to the experimental process; the storage tank and the integrated refrigerator are arranged at the lower part in the body in parallel, the injection pump and the double-needle liquid transfer arm are both arranged at the upper part in the body, the high-temperature incubator is arranged at the middle part of the body, the reagent box, the 2 large high-temperature incubators and the 2 small high-temperature incubators are transversely arranged and arranged on the reference platform, and the injection pump is communicated with the storage tank through a liquid path system; the double-needle pipetting arm realizes the movement of the mechanical arm through a pipetting arm driving mechanism, and the moving direction is vertical to the plane movement of the sampling needle. The invention improves the number of the glass slides processed at one time, reduces the difference of heat treatment among the glass slides, and improves the quality and the efficiency of the glass slide processing.

Description

Full-automatic immunohistochemical dyeing equipment
Technical Field
The invention relates to the technical field of immunohistochemical staining, in particular to full-automatic immunohistochemical staining equipment.
Background
The prior similar products mainly have the following defects:
(1) at present, the handling capacity of instruments and specimens is small in related field automation equipment in the worldwide market, and only 10-70 glass slides are used;
(2) most of the automatic equipment in the related fields in the current world market use single X/Y/Z single-degree-of-freedom motion, and the single action time is long, so that the whole test process period is long;
(3) at present, automatic equipment in related fields in the world market adopts independent temperature control of each glass slide, or integral temperature control precision is not high, so that the test quality of the glass slide is influenced;
(4) at present, reagents are dripped from the upper side of a glass slide by related field automatic equipment in the worldwide market, and the sample adding position cannot ensure the complete coverage of a sample due to the fact that the positioning precision is not in place, so that the glass slide test quality is influenced.
Disclosure of Invention
The invention aims to provide a full-automatic immunohistochemical staining device, which can increase the number of slides to be treated at one time, reduce the difference of heat treatment among the slides, and improve the quality and the treatment efficiency of the slide treatment.
The technical scheme of the invention is that the full-automatic immunohistochemical staining equipment comprises a body 1, an injection pump 2, a double-needle pipetting arm 4, a pipetting arm driving mechanism, a cleaning tank 6, a reagent mixing tank 7, a reagent box 8, a high-temperature incubator 9, an integrated refrigerator 10, a liquid path system, a storage tank, a desktop host 005, a double-group output power source 007, a control circuit board 009 and a reference platform 13; the desktop host 005 is provided with an immunohistochemical experiment flow module, and the flow module accurately controls the experiment flow of the dyeing equipment, namely the desktop host 005 controls the injection pump 2, the double-needle pipetting arm 4, the liquid path system and the high-temperature incubator 9 through the control circuit board 009 according to the experiment flow in the flow module; the control circuit board 009 has digital/analog conversion and signal amplification functions; the double-group output power source 007 is a power supply device in the dyeing equipment;
the body 1 is of a box body structure, a reference platform 13 is fixed on the front side of the middle part of the body 1, a storage box and an integrated refrigerator 10 are arranged at the lower part in the body 1 in parallel, and the storage box comprises a purified liquid storage box 11 and a waste liquid storage box 12; the injection pump 2 and the double-needle pipetting arm 4 are both arranged at the upper part in the body 1, the high-temperature incubator 9 is arranged at the middle part of the body 1, the high-temperature incubator 9 comprises 2 large high-temperature incubators 90 and 2 small high-temperature incubators 91, the reagent box 8, the 2 large high-temperature incubators 90 and the 2 small high-temperature incubators 91 are transversely arranged and arranged on the reference platform 13, the injection pump 2 is fixed at the top end of the upper part of the body 1, and the injection pump 2 is communicated with the storage box through a liquid path system; the reagent mixing tank 7 is embedded in the cleaning tank 6, the cleaning tank 6 is embedded in the base 701, the base 701 is fixedly arranged on the partition plate 013, the reagent mixing tank is positioned in the moving direction of the mechanical arm in the double-needle pipetting arm 4, the double-needle pipetting arm 4 is fixed on the body, the double-needle pipetting arm 4 realizes the movement of the mechanical arm through the pipetting arm driving mechanism, and the moving direction is vertical to the plane movement of the sample adding needle; the inlet of 2 syringe pumps 2 passes through the pipeline and communicates with clean liquid bin 11, and the liquid outlet of 2 syringe pumps 2 passes through the pipeline and is connected with the application of sample needle 401 on moving liquid arm 4, and the overflow mouth of 2 big high temperature incubators 90 and the overflow mouth of 2 little high temperature incubators 91 all communicate with waste liquid bin 120.
The large high-temperature incubator 90 comprises a heating pot 901, a temperature sensor 902, a cover plate bracket 903, a cover plate 904, an incubator sliding guide rail 905, a constant-temperature water bath box 906, an incubator bottom plate and a heating plate; the heating pot 901 is embedded in the constant temperature water bath box 906, a plurality of cover plate supports 903 are transversely arranged in parallel in the heating pot 901 along the heating pot 901, a plurality of cover plate grooves are arranged in the cover plate supports 903, the cover plate grooves are arranged along the longitudinal direction of the heating pot 901, 1 cover plate 904 is buckled on each cover plate groove, a plurality of glass slides are respectively attached to the inner surfaces of the cover plates 904, 2 incubator sliding guide rails 905 are respectively and fixedly arranged on the inner sides of two incubator supporting plates, 2 incubator supporting plates are respectively arranged on two sides of the constant temperature water bath box 906, a heating plate is fixedly arranged at the bottom of the heating pot 901, 2 incubator guide blocks are fixedly arranged on two side surfaces of the constant temperature water bath box 906, 2 incubator guide blocks are respectively and slidably connected with the 2 incubator sliding guide rails 905, the 2 incubator supporting plates are respectively and fixedly arranged on the incubator bottom plates through 1 supporting shaft, the purified liquid 11 is communicated with a liquid inlet 901 of the heating pot through a pipeline, the liquid outlet of the heating pot 901 is communicated with the waste liquid storage tank 12, the temperature sensor 902 is fixedly installed at the inner side of the heating pot 901, the soleplate of the incubator is fixedly installed on the reference platform 13, and the heating pot 901 is filled with liquid.
The high temperature incubator 90 houses three cover holders 903, one for a maximum of 16 covers.
The volume of water or repair liquid added in the large high-temperature incubator 90 is 2/3 of the volume of the heating pan 901, and the volume of water or repair liquid added in the small high-temperature incubator 91 is 2/3 of the volume of the heating pan 911.
The pipetting arm driving mechanism comprises a motor 406, a support slide rail 407 and a base rack 405; a support sliding rail 407 is fixed on an output shaft of the motor 406, gear teeth are arranged on the support sliding rail 407, the gear teeth on the support sliding rail 407 are meshed with the base rack 405, and the mechanical arm is fixedly connected with the base gear.
The liquid path system comprises a relay 001, an electromagnetic valve, a pressure valve 003 and a diaphragm pump 004; the purified liquid storage tank 11 comprises a pure water storage tank 110 and a repair liquid storage tank 111; 2 the inlet of individual syringe pump 2 passes through the pipeline and communicates with pure water storage tank 110, 1 solenoid valve is connected separately to pure water storage tank 110 and repair liquid storage tank 111, 2 solenoid valves all are connected with feed liquor diaphragm pump 004 inlet, the inlet of pressure valve 003 is connected with diaphragm pump 004 liquid outlet, the liquid outlet of pressure valve 003 falls into four ways, four ways communicate with 2 big high temperature incubator 90 inlets and 2 little high temperature incubator 91 inlets respectively through respective solenoid valve, 2 the liquid outlet of 2 big high temperature incubator 90 and the liquid outlet of 2 little high temperature incubator 91 are connected with flowing back diaphragm pump 010 inlet through the solenoid valve respectively, two way pipelines are divided into to the liquid outlet of flowing back diaphragm pump 010, a solenoid valve is respectively connected to two way pipelines, 2 solenoid valves respectively with general waste liquid storage tank 120, special waste liquid storage tank 121 communicates.
The reagent box 8 comprises a reagent rack 801, reagent bottles 802, a large reagent groove 803, a reagent sliding guide rail 804, a reagent supporting plate 805, a reagent supporting shaft 806, a reagent box body 807 and a reagent bottom plate 808; 2 reagent sliding guide rails 804 are respectively and fixedly installed on the inner sides of the two reagent supporting plates 805, 2 reagent supporting plates 805 are respectively located on two sides of the reagent box body 807, 2 reagent supporting plates are respectively and fixedly installed on the reagent bottom plate 808 through 1 reagent supporting shaft 806, 2 reagent guide blocks are respectively and fixedly installed on two side surfaces of the reagent box body 807, and 2 reagent guide blocks are respectively and slidably connected with the 2 reagent sliding guide rails 804; a plurality of reagent racks 801 and a large reagent groove 803 are transversely arranged and placed in a box body 807, a plurality of reagent grooves are arranged in each reagent rack 801, and each reagent groove is buckled with one reagent bottle 802.
The cleaning tank 6 is provided with four separated cleaning holes, and the cleaning depth of two paths of cleaning holes in the four paths of cleaning holes is 0-35 mm, so that the cleaning tank is used for cleaning the sample adding needle 401 which is used for taking out the conductive reagent; the cleaning depth of the two paths of cleaning holes is 0-85 mm, and the two paths of cleaning holes are used for cleaning the sample adding needle 401 which is used for taking the non-conducting reagent; the cleaned waste liquid is directly connected with a special waste liquid storage 121 box through a pipeline.
The number of the control circuit boards 009 is 4, and one control circuit board 009 controls one high temperature incubator.
The dyeing apparatus further comprises a gate control switch 3; the door control switch 3 is installed on the upper portion in the body 1, and the door is connected with the body rotation, and door control switch 3 fixed mounting is in the pivot department of door and body to door control switch 3 is connected to control circuit board 009 through the wire, and when the door of equipment was opened and was 20 jiaos with the body in the experimentation, was in the open mode promptly, door control switch 3 triggered the bee calling organ on the control circuit board 009 and sounded.
The beneficial effect of the invention is that,
(1) the invention has large sample processing capacity, and can process 160 glass slides at most at one time;
(2) in the invention, a plurality of glass slides in the same test are integrally heated, but each glass slide is separately heated and independently temperature-controlled, so that the difference of heat treatment among the glass slides is reduced, and the quality and consistency of glass slide treatment are improved;
(3) under the control of a desktop host of the device, a double-needle liquid transfer arm moves in an X/Y/Z free space, a sample adding needle accurately moves right above a test glass slide of a high-temperature incubator to carry out reagent drip irrigation, and when a reagent is added, the dropped reagent permeates from the top to the bottom between the glass slides and gradually flows out from the bottom of the glass slide;
(4) the invention arranges two sample adding needles on the mechanical arm, which improves the sampling and sample adding efficiency, the sampling volume of the sample adding needle is 5 to 5000 μ L, the sample adding precision is high, and the range is wide.
(5) The liquid level and temperature sensors are arranged in different liquid storage tanks, so that the liquid capacity and temperature can be sensed and measured at any time.
(6) The sample adding needle can be a plurality of continuous or a plurality of spaced slides in the high-temperature incubator, different slides can adopt different test flows in software, and four incubators can run four different test flows.
(7) The invention is provided with a built-in refrigerator, and reagents needing to be refrigerated can be directly stored in the built-in refrigerator of the device without additionally arranging refrigeration equipment.
(8) The desktop host and the display screen are arranged in the device, all experimental processes can be completed on the device, and external devices are not needed.
The invention adopts the structural design of integrating the improvement of the number of the glass slides processed at one time, the combination of the comprehensive temperature control incubator and the effective low-temperature storage of the standby reagent, thereby solving the problems that the number of the glass slides is small in processing, the high-temperature heat treatment needs to be realized by external equipment and the reagent used by the equipment needs to be stored by independent equipment in the existing test process. The invention improves the number of the glass slides processed at one time, reduces the difference of heat treatment among the glass slides, and improves the quality and the efficiency of the glass slide processing; the invention realizes the consistency, repeatability and reliability of the slide test through the full-automatic control flow, reduces the interference of human factors and greatly improves the operation efficiency.
Drawings
FIG. 1 is a schematic structural diagram of a fully automatic immunohistochemical staining apparatus according to the present invention;
FIG. 2 is a rear view of the interior of the present invention;
FIG. 3 is a top view of FIG. 2;
FIG. 4 is an exploded view of the high temperature incubator of the present invention;
FIG. 5 is an exploded view of the reagent kit of the present invention;
FIG. 6 is a schematic view showing the construction of a reagent mixing tank and a cleaning tank according to the present invention;
FIG. 7 is a schematic diagram of the connection of the fluid path system of the present invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, it should be noted that the terms "upper", "lower", "left", "right", "inner", "outer", etc. indicate orientations or positional relationships based on those shown in the drawings, which are merely for convenience of description and simplicity of description, but do not mean or imply that the designated devices or elements must have a specific orientation, and furthermore, the terms "mounted" and "connected" in the description of the present invention should be construed broadly.
The technical scheme of the invention is further described in detail by combining the drawings and the embodiments in the specification.
As shown in fig. 1, the full-automatic immunohistochemical staining apparatus of the present invention includes a body 1, an injection pump 2, a gate control switch 3, a double-needle pipetting arm 4, a pipetting arm driving mechanism, a display screen 5, a rinsing tank 6, a reagent mixing tank 7, a reagent tank 8, a high temperature incubator 9, an integrated refrigerator 10, a liquid path system, a storage tank, a desktop host 005, an exhaust fan 006, a double-group output power source 007, a weight-reducing beam 008, a control circuit board 009, and a reference platform 13. The control circuit board 009 is connected with the host desktop computer 005 through cables, and the control circuit board 009 is connected with each device in the injection pump 2, the double-needle pipetting arm 4, the high-temperature incubator 9, the gate control switch and the liquid path system through cables. Desktop host computer 005 carries on the immunohistochemical experiment flow module, and the flow module carries out accurate control to the experiment flow of this equipment, and desktop host computer 005 passes through control circuit board 009 according to the experiment flow in the flow module and realizes controlling syringe pump 2, double-needle move liquid arm 4, liquid way system, high temperature incubator 9 and gate switch promptly. The control circuit board 009 has digital/analog conversion and signal amplification functions. The double-group output power source 007 is a power supply device in the dyeing equipment.
The body 1 is a box structure. The reference platform 13 is L-shaped, and the reference platform 13 is fixed on the front side of the middle part of the body 1. The storage box and the integrated refrigerator 10 are juxtaposed at a lower portion in the body 1. The storage tanks comprise a clean liquid storage tank 11 and a waste liquid storage tank 12; the clean liquid storage tank 11 is located above the waste liquid storage tank 12. The display screen 5, the injection pump 2, the gate control switch 3 and the double-needle liquid-transferring arm 4 are all arranged on the upper part in the body 1. The high-temperature incubator 9 is installed in the middle of the body 1. The high-temperature incubator 9 comprises 2 large high-temperature incubators 90 and 2 small high-temperature incubators 91, the reagent box 8, the 2 large high-temperature incubators 90 and the 2 small high-temperature incubators 91 are transversely arranged and installed on the reference platform 13, and the injection pump 2 is fixed at the top end of the upper part of the body 1. The syringe pump 2 is communicated with the storage tank through a fluid path system.
The embedding of reagent mixing tank is settled in washing tank 6, for detachable construction, and washing tank 6 embedding is settled in base 701, is detachable construction again. The base 701 is fixed to the partition 013 by a screw fitting, and the reagent mixing well is positioned in the direction of movement of the mechanical arm in the double-needle pipetting arm 4. After the desktop host 005 identifies the number of loaded slides, the required reagent amount is calculated, the corresponding reagent is extracted from the reagent box 8 by the sample adding needle 401, the sample adding needle 401 moves to the position above the reagent mixing tank 7 under the control of the desktop host 005, the required reagent proportion is completed, and the proportion is controlled by a flow module in the desktop host 005.
The bin gate is rotationally connected with the body to seal the body. The door control switch 3 is fixed at a rotating shaft of the bin door and the body through screws, the door control switch 3 is connected to the control circuit board 009 through a lead, and when the bin door of the device is opened and forms an angle of 20 degrees with the bin door in the experimental process, namely, in an opening state, a buzzer on the control circuit board 009 can be directly triggered to emit buzzing sound, and meanwhile, the display can give corresponding prompts.
The double needle moves liquid arm 4 and adopts now, and double needle moves liquid arm 4 and fixes on the body, and double needle moves liquid arm 4 promptly and adopts the fix with screw in the backup pad 011 above reducing weight roof beam 008. Namely, the support plate 011 is fixed on the upper part of the weight reducing beam 008 through screws, then the double needle liquid transferring arm 4 is fixed on the support plate 011, and the weight reducing beam 008 is fixed on the body.
The double-needle pipetting arm 4 comprises a sample adding needle 401, a scanner 402, a support slide rail 403, a mechanical arm 404, a base 405 and a driving motor 406. The number of the sample adding needles 401 in the double-needle pipetting arm 4 is 2, wherein the scanner 402 moves along with the sample adding needles 401, the scanner 402 automatically identifies two-dimensional codes of slides and reagent bottles to extract information of the slides and the reagents, and the desktop host 005 calculates the amount of the reagents required by the test according to the slide information (such as patient case information, position information of the slides and corresponding slide reagent distribution information in the test process) output by the scanner 402.
The sample adding needle in the double-needle liquid transferring arm 4 has two vertical movements relative to the mechanical arm, namely, the movement of the sample adding needle on the Y axis and the Z axis is realized through a motor and a gear mechanism in the mechanical arm. The double-needle pipetting arm 4 realizes the movement in the other vertical direction through the pipetting arm driving mechanism, namely, the mechanical arm can freely move in the X direction. The pipetting arm drive mechanism comprises a motor 406, a support slide 407 and a base rack 405. A support sliding rail 407 is fixed on an output shaft of the motor 406, gear teeth are arranged on the support sliding rail 407, the gear teeth on the support sliding rail 407 are meshed with the base rack 405, and the mechanical arm is fixedly connected with the base gear. After the double-needle pipetting arm 4 is electrified, the motor 406 operates under the control of the desktop host 005 and drives the support slide rail 407 to rotate, and the base rack 405 is further driven to move, so that the mechanical arm moves in the X direction. Finally, the double-needle pipetting arm 4 realizes X/Y/Z-axis multi-degree-of-freedom motion. It should be noted that the movement in each direction is precisely controlled by the desktop computer.
As shown in fig. 6, the liquid path system includes a relay 001, an electromagnetic valve 002, a pressure valve 003, and a diaphragm pump 004, the liquid inlets of the 2 injection pumps 2 are communicated with the pure water storage tank 110 through pipelines, and the liquid outlets of the 2 injection pumps 2 are connected with the sample adding needle 401 on the liquid transferring arm 4 through pipelines. Pure water storage tank 110 and restoration liquid storage tank 111 connect 1 solenoid valve 002 separately, and 2 solenoid valves 002 all are connected with feed liquor diaphragm pump 004 inlet, and the inlet and the diaphragm pump 004 liquid outlet of pressure valve 003 are connected, and the liquid outlet of pressure valve 003 falls into four ways, and four ways communicate with the inlet of 2 big high temperature incubator 90 inlets and 2 little high temperature incubators 91 respectively through respective solenoid valve 002. The liquid outlet of 2 big high temperature incubator 90 and the liquid outlet of 2 little high temperature incubator 91 are connected with flowing back diaphragm pump 010 inlet through solenoid valve 002 respectively. The liquid outlet of flowing back diaphragm pump 010 falls into two way pipelines, and two way pipelines respectively connect an electromagnetic valve, and 2 electromagnetic valves communicate with waste liquid storage tank 120, special waste liquid storage tank 121 respectively. The overflow ports of the 2 large high-temperature incubators 90 and the overflow ports of the 2 small high-temperature incubators 91 are both communicated with the waste liquid storage tank 120.
The purified liquid storage tank 11 comprises a pure water storage tank 110 and a repair liquid storage tank 111; the waste liquid storage tank 12 includes a general waste liquid storage tank 120 and a special waste liquid storage tank 121. The waste liquid is the waste liquid which is used after pure water is utilized and has no reagent pollution, such as: pure water used for cooling the high-temperature incubator is designated as a general waste liquid when being discharged. The special waste liquid refers to a waste liquid containing a reagent component in a discharged waste liquid, such as a liquid in which pure water and a repairing liquid are mixed in proportion when a slide is subjected to antigen repairing, and is designated as a special waste liquid when discharged.
The reagent box 8 comprises a reagent rack 801, reagent bottles 802, a large reagent groove 803, a reagent sliding guide rail 804, a reagent supporting plate 805, a reagent supporting shaft 806, a reagent box body 807 and a reagent bottom plate 808; 2 reagent sliding guide rails 804 are respectively and fixedly installed on the inner sides of the two reagent supporting plates 805, 2 reagent supporting plates 805 are respectively located on two sides of the reagent box body 807, 2 reagent supporting plates are respectively and fixedly installed on the reagent bottom plate 808 through 1 reagent supporting shaft 806, 2 reagent guide blocks are respectively and fixedly installed on two side surfaces of the reagent box body 807 through screws, and 2 reagent guide blocks are respectively and slidably connected with the 2 reagent sliding guide rails 804; a plurality of reagent racks 801 and a large reagent groove 803 are transversely arranged and placed in a box body 807, a plurality of reagent grooves are arranged in each reagent rack 801, and each reagent groove is buckled with one reagent bottle 802.
As shown in fig. 4, the large high-temperature incubator 90 includes a heating pan 901, a temperature sensor 902, a cover plate bracket 903, a cover plate 904, an incubator sliding guide 905, a constant-temperature water bath 906, an incubator bottom plate, and a heating plate; the heating pan 901 is embedded in the constant temperature water bath 906. A plurality of cover plate brackets 903 are horizontally and parallelly arranged in the heating pan 901 along the heating pan 901, a plurality of cover plate grooves are arranged in the cover plate brackets 903, and the plurality of cover plate grooves are arranged one by one along the length direction of the cover plate brackets 903, namely, are arranged along the longitudinal direction of the heating pan 901. Each cover plate slot is buckled with 1 cover plate 904. A plurality of slides are respectively attached to the inner surfaces of the plurality of cover plates 904. 2 incubator sliding guide 905 respectively fixed mounting are inboard at two incubator backup pads, and 2 incubator backup pads are located the both sides of constant temperature water bath 906 respectively. The hot plate passes through screw fixed mounting in the bottom of heating pot 901, and 2 incubator guide blocks pass through screw fixed mounting respectively on the both sides face of thermostatted water bath 906, 2 incubator guide blocks respectively with 2 incubator sliding guide 905 sliding connection. 2 incubator backup pads are respectively through 1 back shaft fixed mounting on the incubator bottom plate. The purified liquid storage tank 11 is communicated with a liquid inlet of the heating pot 901 through a pipeline. The liquid outlet of the heating pan 901 is communicated with the waste liquid storage tank 12. The temperature sensor 902 is fixedly installed inside the heating pan 901, and the bottom plate of the incubator bottom plate is fixedly installed on the reference platform 13 through screws. The heating pan 901 is filled with liquid, i.e. the thermostat water bath 906 is seated in the liquid. The liquid in the heating pan 901 is water or repair liquid.
The small high-temperature incubator 91 is similar to the large high-temperature incubator 91 in structure, and the small high-temperature incubator 91 comprises a heating pot 911, a temperature sensor 902, a cover plate bracket 912, a cover plate 904, a sliding guide rail 905 and a constant-temperature water bath tank 913; the difference is that the high temperature incubator 9 further comprises a water inlet pipeline interface 920, a water outlet pipeline interface 921 and a self-overflow pipeline interface 922.
In the embodiment of the present invention, the number of the injection pumps 2 is 2, one end of each of the 2 injection pumps 2 is respectively connected to the 2 sample adding needles 401 on the double-needle pipetting arm 4 through a pipeline, and the other end of each of the 2 injection pumps 2 is connected to the pure water storage tank 110 through a pipeline, that is, one injection pump 2 is connected to one sample adding needle 401.
And an exhaust fan 006. The exhaust fan 006 is fixed to the partition plate 013 by means of screws, and the steam generated in the heating pan is drawn away by the exhaust fan 006, and the liquid generated by the steam is discharged into the general waste liquid storage tank 120 through a pipeline at the interface of the exhaust fan 006.
Washing tank 6 is used for wasing application of sample needle outer wall and inner wall, is provided with the washing hole of four separated ways washing application of sample needle outer wall on the washing tank 6, and every washs hole site and corresponds an application of sample needle 401, and application of sample needle stretches into in the washing hole during the washing. In the four cleaning holes, the cleaning depth of two cleaning holes is 0-35 mm, and the cleaning holes are used for cleaning the sample adding needle 401 which is used for completely taking the conductive reagent; the cleaning depth of the two paths of cleaning holes is 0-85 mm, and the two paths of cleaning holes are used for cleaning a sample adding needle 401 which is used for completely taking a non-conducting reagent (such as alcohol and dewaxing liquid); the cleaned waste liquid is directly connected with a special waste liquid storage 121 box through a pipeline.
The reagent cassette 8 can store 5 rows of reagent racks 801 and one row of large reagent tanks 803, and a single row of reagent racks 801 can store 10 reagent bottles 802.
Three rows of cover plate brackets 903 can be placed in one large high-temperature incubator 90, 16 cover plates can be placed in one row of cover plate brackets at most, and 48 cover plates can be placed in three rows of cover plate brackets at most;
the small high-temperature incubator 91 can be used for placing at most two rows of cover plate supports 903, one row of cover plate supports can be used for placing at most 16 cover plates, and the two rows of cover plate supports can be used for placing at most 32 cover plates;
sliding guide rails are arranged on the left side and the right side of the constant-temperature water bath box 906 and the constant-temperature water bath box 913, the reagent rack can be directly drawn out and placed, water inlet pipeline interfaces 920 of the constant-temperature water bath box 906 and the constant-temperature water bath box 913 are connected to the electromagnetic valve 002 through hoses, the electromagnetic valve 002 is connected with the liquid inlet diaphragm pump 004, the constant-temperature water bath box is connected to the pure water storage tank 110 through the water inlet diaphragm pump 004, and the water outlet pipeline interface 921 is also connected to the general waste liquid storage tank; the self-overflow pipe 922 is connected to the general waste liquid storage tank 120 by a hose.
The clean liquid storage tank 11 and the waste liquid storage tank 12 are both provided with liquid level detection devices, the volume in the storage tanks can be detected in real time, and when a certain volume is reached, the desktop host 005 can prompt an operator to process the clean liquid storage tank.
The temperature sensor 902 is provided in the constant temperature water bath tank 9, and the temperature sensor 902 must be installed below the liquid level. The temperature of the water or the repair liquid in the high-temperature incubator 9 can be fed back to the desktop host 005 in real time.
The cleaning tank 6 and the reagent mixing tank 7 are detachably mounted on a partition plate above the reference platform 13.
The number of the diaphragm pumps 004 arranged below the back of the double-needle pipetting arm 4 is 2, the number of the pressure valves 003 is 1, the number of the electromagnetic valves 002 is 12, and the number of the relays 001 is 5; wherein 1 relay 001 is used for controlling the exhaust fan, and the rest are used for controlling the high-temperature incubator. In addition, the single high-temperature incubator 6 uses two electromagnetic valves 002, the rest are shared electromagnetic valves 002, all the connection modes are pipeline connection, and sealing measures are provided at corresponding interfaces.
The number of the control circuit boards 009 is 4, and the single control circuit board 009 controls one high temperature incubator 9.
The integrated refrigerator 10 is mainly used for storing some special reagents needing refrigeration and directly putting the unused reagents into the refrigerator after the test is finished, wherein the refrigerating chamber capacity of the refrigerator is 68L, and the freezing chamber capacity of the refrigerator is 17L.
The double-needle pipetting arm 4 drives the mechanical arm 404 and the sampling needle 401 through an internal motor, so that three-axis multi-free motion is realized.
The gate control switch 3 is used for warning the opening or closing of the bin gate of the immunohistochemical equipment in the experimental process, when the bin gate is opened during the experiment of the equipment, the gate control switch feeds back to the control system in time and the control system gives an alarm.
The volume of water or repair liquid added in the large high-temperature incubator 90 is 2/3 of the volume of the heating pan 901, and the volume of water or repair liquid added in the small high-temperature incubator 91 is 2/3 of the volume of the heating pan 911.
The heating pan 901 is used for heating liquid, and sealing measures are provided at all pipeline joints. The incubator sliding guide 905 is a three-section silent undamped guide. The cover plate 904 can hold only one slide 9 per sheet. The slide 9 is to be adaptively attached to the cover plate 904 and must not be pressed hard.
The experimental process adopted by the invention is that,
(1) firstly, placing a glass slide and a cover plate on a cover plate bracket;
(2) preparing reagents required by the test, and placing the reagents at corresponding positions of the reagent areas;
(3) placing the cover plate supports with the glass slides on the reference platforms of the corresponding high-temperature incubator respectively;
(4) the immunohistochemical equipment is started, namely the desktop host is started after a power switch is turned on. Each part of the device automatically operates according to a predetermined experimental process under the control of a desktop host, two sample adding needles, namely a liquid sucking needle, respectively suck DAB staining solution A and DAB staining solution B, then move to a reagent mixing tank 7 area, and add two reagents into the same reagent bottle in the area, thereby preparing a DAB staining reagent;
(5) adding a staining reagent onto the slide by a double-needle pipetting arm;
(6) waiting for a staining module to stain the glass slide;
(7) after the slides were completely stained, the operator removed the slides.
Set up the test step on the bench-top host computer, the scanner automatic identification slide glass, the two-dimensional code of reagent bottle, draw slide glass and reagent information, the bench-top host computer calculates the required reagent volume of this experiment according to the slide information automatic calculation that scans, and the liquid needle can also explore reagent liquid level degree of depth when getting liquid, calculate the reagent surplus, if the reagent is not enough before the experiment begins, equipment can automatic alarm, add drainage device, heating device, move the liquid arm, illumination pilot lamp and alarm device etc. according to the automatic operation of test step, thereby realize the full automatic control of experimentation. When the slide glass carries out the experiment, the scanner scans the two-dimensional code on slide glass, the reagent bottle and draws slide glass and reagent information, set up experimental step on desk top host computer, move the liquid arm by software drive double needle and remove the liquid arm and remove the slide glass and correspond the position and carry out reagent and add, desk top host computer passes through temperature sensor's in the incubator feedback to the temperature of liquid in the control incubator, the incubator realizes antigen restoration reliability through the accurate control mode of high temperature, drip irrigation the maximize through the application of sample needle accuracy and guarantee that tissue surface reagent is even. The device realizes the consistency, repeatability and reliability of the slide test through a full-automatic control flow, reduces the interference of human factors and greatly improves the operation efficiency.
The above description is only for the purpose of illustrating the present invention and the appended claims, and it should be understood by those skilled in the art that the present invention is not limited thereto, but can be implemented by those skilled in the art.

Claims (10)

1. A full-automatic immunohistochemical dyeing equipment is characterized in that: the dyeing equipment comprises a body (1), an injection pump (2), a double-needle liquid-transferring arm (4), a liquid-transferring arm driving mechanism, a cleaning tank (6), a reagent mixing tank (7), a reagent box (8), a high-temperature incubator (9), an integrated refrigerator (10), a liquid path system, a storage tank, a desktop host (005), a double-group output power supply (007), a control circuit board (009) and a reference platform (13); the desktop host (005) is provided with an immunohistochemical experiment flow module, the flow module accurately controls the experiment flow of the dyeing equipment, namely the desktop host (005) controls the injection pump (2), the double-needle liquid transfer arm (4), the liquid path system and the high-temperature incubator (9) through the control circuit board (009) according to the experiment flow in the flow module; the control circuit board (009) has digital/analog conversion and signal amplification functions; the double-group output power supply (007) is a power supply device in the dyeing equipment;
the body (1) is of a box body structure, the reference platform (13) is fixed on the front side of the middle part of the body (1), the storage box and the integrated refrigerator (10) are arranged on the lower part in the body (1) in parallel, and the storage box comprises a clean liquid storage box (11) and a waste liquid storage box (12); the injection pump (2) and the double-needle liquid transfer arm (4) are both arranged on the upper part in the body (1), the high-temperature incubator (9) is arranged in the middle of the body (1), the high-temperature incubator (9) comprises 2 large high-temperature incubators (90) and 2 small high-temperature incubators (91), the reagent box (8), the 2 large high-temperature incubators (90) and the 2 small high-temperature incubators (91) are transversely arranged on the reference platform (13), the injection pump (2) is fixed at the top end of the upper part of the body (1), and the injection pump (2) is communicated with the storage box through a liquid path system; the reagent mixing tank (7) is embedded in the cleaning tank (6), the cleaning tank (6) is embedded in the base (701), the base (701) is fixedly mounted on the partition plate (013), the reagent mixing tank is located in the mechanical arm moving direction in the double-needle pipetting arm (4), the double-needle pipetting arm (4) is fixed on the body, the double-needle pipetting arm (4) realizes the movement of the mechanical arm through the pipetting arm driving mechanism, and the moving direction is perpendicular to the plane movement of the sample adding needle; the liquid inlet of 2 injection pumps (2) is communicated with the clean liquid storage tank (11) through a pipeline, the liquid outlet of 2 injection pumps (2) is connected with a sample adding needle (401) on the liquid transferring arm (4) through a pipeline, and the overflow ports of 2 large high-temperature incubators (90) and the overflow ports of 2 small high-temperature incubators (91) are communicated with the waste liquid storage tank (120).
2. The fully automatic immunohistochemical staining apparatus according to claim 1, wherein: the large high-temperature incubator (90) comprises a heating pot (901), a temperature sensor (902), a cover plate bracket (903), a cover plate (904), an incubator sliding guide rail (905), a constant-temperature water bath box (906), an incubator bottom plate and a heating plate; the heating pot (901) is embedded in the constant temperature water bath box (906), a plurality of cover plate brackets (903) are transversely arranged in the heating pot (901) in parallel along the heating pot (901), a plurality of cover plate grooves are arranged in the cover plate brackets (903), the plurality of cover plate grooves are longitudinally arranged along the heating pot (901), 1 cover plate (904) is buckled on each cover plate groove, a plurality of glass slides are respectively attached to the inner surfaces of the plurality of cover plates (904), 2 incubator sliding guide rails (905) are respectively and fixedly arranged on the inner sides of two incubator supporting plates, 2 incubator supporting plates are respectively positioned on two sides of the constant temperature water bath box (906), the heating plate is fixedly arranged at the bottom of the heating pot (901), 2 incubator guide blocks are fixedly arranged on two side surfaces of the constant temperature water bath box (906), the 2 incubator guide blocks are respectively and slidably connected with the 2 incubator sliding guide rails (905), the 2 incubator supporting plates are respectively and fixedly arranged on the bottom plates of the incubator through 1 supporting shaft, the purified liquid storage tank (11) is communicated with a liquid inlet of the heating pot (901) through a pipeline, a liquid outlet of the heating pot (901) is communicated with the waste liquid storage tank (12), the temperature sensor (902) is fixedly installed on the inner side of the heating pot (901), a soleplate of the incubator is fixedly installed on a reference platform (13), and the heating pot (901) is filled with liquid.
3. The fully automatic immunohistochemical staining apparatus according to claim 2, wherein: the high-temperature incubator (90) is provided with three cover plate brackets (903), and one cover plate bracket is provided with 16 cover plates at most.
4. The fully automatic immunohistochemical staining apparatus according to claim 2, wherein: the volume of the water or the repair liquid added in the large high-temperature incubator (90) is 2/3 of the volume of the heating pan (901), and the volume of the water or the repair liquid added in the small high-temperature incubator (91) is 2/3 of the volume of the heating pan (911).
5. The fully automatic immunohistochemical staining apparatus according to claim 1, wherein: the pipetting arm driving mechanism comprises a motor (406), a support sliding rail (407) and a base rack (405); a support sliding rail (407) is fixed on an output shaft of the motor (406), gear teeth are arranged on the support sliding rail (407), the gear teeth on the support sliding rail (407) are meshed with the base rack (405), and the mechanical arm is fixedly connected with the base gear.
6. The fully automatic immunohistochemical staining apparatus according to claim 1, wherein: the liquid path system comprises a relay (001), an electromagnetic valve, a pressure valve (003) and a diaphragm pump (004); the purified liquid storage tank (11) comprises a pure water storage tank (110) and a repairing liquid storage tank (111); the inlet of 2 injection pumps 2 passes through pipeline and pure water bin (110) intercommunication, 1 solenoid valve is connected separately in pure water bin (110) and repair liquid bin (111), 2 solenoid valves all are connected with feed liquor diaphragm pump (004) inlet, the inlet of pressure valve (003) is connected with diaphragm pump (004) liquid outlet, the liquid outlet of pressure valve (003) falls into four ways, four ways are connected with the inlet of 2 big high temperature incubator (90) inlets and 2 little high temperature incubator (91) inlets respectively through respective solenoid valve, the liquid outlet of 2 big high temperature incubator (90) and the liquid outlet of 2 little high temperature incubator (91) are connected with flowing back diaphragm pump (010) inlet through the solenoid valve respectively, the liquid outlet of flowing back diaphragm pump (010) falls into two way pipelines, two way pipelines respectively connect a solenoid valve, 2 solenoid valves respectively with general waste liquid bin (120), The special waste liquid storage tank (121) is communicated.
7. The fully automatic immunohistochemical staining apparatus according to claim 1, wherein: the reagent box (8) comprises a reagent rack (801), reagent bottles (802), a large reagent groove (803), a reagent sliding guide rail (804), a reagent supporting plate (805), a reagent supporting shaft (806), a reagent box body (807) and a reagent bottom plate (808); 2 reagent sliding guide rails (804) are respectively and fixedly arranged on the inner sides of the two reagent supporting plates (805), 2 reagent supporting plates (805) are respectively positioned on two sides of a reagent box body (807), 2 reagent supporting plates are respectively and fixedly arranged on a reagent bottom plate (808) through 1 reagent supporting shaft (806), 2 reagent guiding blocks are respectively and fixedly arranged on two side surfaces of the reagent box body (807), and 2 reagent guiding blocks are respectively and slidably connected with the 2 reagent sliding guide rails (804); a plurality of reagent racks (801) and a large reagent groove (803) are transversely arranged and placed in a box body (807), a plurality of reagent grooves are arranged in each reagent rack (801), and each reagent groove is buckled with one reagent bottle (802).
8. The fully automatic immunohistochemical staining apparatus according to claim 1, wherein: the cleaning tank (6) is provided with four separated cleaning holes, and the cleaning depth of two paths of cleaning holes in the four paths of cleaning holes is 0-35 mm, so that the cleaning tank is used for cleaning a sample adding needle (401) which is used for taking out a conductive reagent; the cleaning depth of the two paths of cleaning holes is 0-85 mm, and the two paths of cleaning holes are used for cleaning a sample adding needle (401) which is used for completely taking the non-conducting reagent; the cleaned waste liquid is directly connected with a special waste liquid storage tank (121) through a pipeline.
9. The fully automatic immunohistochemical staining apparatus according to claim 1, wherein: the number of the control circuit boards (009) is 4, and one control circuit board (009) controls one high-temperature incubator.
10. The fully automatic immunohistochemical staining apparatus according to claim 1, wherein: the dyeing apparatus further comprises a gate switch (3); the door control switch (3) is installed on the upper portion in the body (1), the bin gate is connected with the body in a rotating mode, the door control switch (3) is fixedly installed on a rotating shaft of the bin gate and the body, the door control switch (3) is connected to the control circuit board (009) through a conducting wire, and when the bin gate of the device is opened to form an angle of 20 degrees with the body in the experimental process, namely, when the bin gate is in an opening state, the door control switch (3) triggers a buzzer on the control circuit board (009) to emit buzzing sound.
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CN111912995A (en) * 2020-08-10 2020-11-10 英诺维尔智能科技(苏州)有限公司 High-flux flexible tissue sample analysis system
CN111929432A (en) * 2020-08-10 2020-11-13 英诺维尔智能科技(苏州)有限公司 Operation method of high-throughput flexible tissue sample analysis system
CN112051122A (en) * 2020-09-15 2020-12-08 重庆拓谱生物工程有限公司 Sample applicator
CN112354494A (en) * 2020-10-30 2021-02-12 南京北成光生物科技有限公司 Multichannel liquid way incubation detects flowing back integration measuring chamber
CN114152496A (en) * 2021-12-31 2022-03-08 河南赛诺特生物技术有限公司 Automatic immunohistochemical dyeing machine
CN114323833A (en) * 2021-09-30 2022-04-12 北京海格莱生物科技有限公司 Immunohistochemical specimen processing device and method adopting paraffin section mode
CN116008574A (en) * 2022-12-14 2023-04-25 黑龙江八一农垦大学 Immune group ization all-in-one
CN118090379A (en) * 2024-04-26 2024-05-28 苏州百道医疗科技有限公司 Immunohistochemical staining instrument

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CN110849695A (en) * 2019-11-26 2020-02-28 苏州百道医疗科技有限公司 Full-automatic immunohistochemical system
CN213068417U (en) * 2020-03-25 2021-04-27 北京海格莱生物科技有限公司 Full-automatic immunohistochemical dyeing equipment

Patent Citations (2)

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Publication number Priority date Publication date Assignee Title
CN110849695A (en) * 2019-11-26 2020-02-28 苏州百道医疗科技有限公司 Full-automatic immunohistochemical system
CN213068417U (en) * 2020-03-25 2021-04-27 北京海格莱生物科技有限公司 Full-automatic immunohistochemical dyeing equipment

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111912995A (en) * 2020-08-10 2020-11-10 英诺维尔智能科技(苏州)有限公司 High-flux flexible tissue sample analysis system
CN111929432A (en) * 2020-08-10 2020-11-13 英诺维尔智能科技(苏州)有限公司 Operation method of high-throughput flexible tissue sample analysis system
CN112051122A (en) * 2020-09-15 2020-12-08 重庆拓谱生物工程有限公司 Sample applicator
CN112354494A (en) * 2020-10-30 2021-02-12 南京北成光生物科技有限公司 Multichannel liquid way incubation detects flowing back integration measuring chamber
CN114323833A (en) * 2021-09-30 2022-04-12 北京海格莱生物科技有限公司 Immunohistochemical specimen processing device and method adopting paraffin section mode
CN114152496A (en) * 2021-12-31 2022-03-08 河南赛诺特生物技术有限公司 Automatic immunohistochemical dyeing machine
CN116008574A (en) * 2022-12-14 2023-04-25 黑龙江八一农垦大学 Immune group ization all-in-one
CN118090379A (en) * 2024-04-26 2024-05-28 苏州百道医疗科技有限公司 Immunohistochemical staining instrument
CN118090379B (en) * 2024-04-26 2024-06-21 苏州百道医疗科技有限公司 Immunohistochemical staining instrument

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