WO2017162150A1 - 一种载片标本检测的热处理装置 - Google Patents

一种载片标本检测的热处理装置 Download PDF

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Publication number
WO2017162150A1
WO2017162150A1 PCT/CN2017/077572 CN2017077572W WO2017162150A1 WO 2017162150 A1 WO2017162150 A1 WO 2017162150A1 CN 2017077572 W CN2017077572 W CN 2017077572W WO 2017162150 A1 WO2017162150 A1 WO 2017162150A1
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WO
WIPO (PCT)
Prior art keywords
slide
container
specimen
heat treatment
carrier
Prior art date
Application number
PCT/CN2017/077572
Other languages
English (en)
French (fr)
Inventor
郭金灿
郭恩明
Original Assignee
广州深达生物制品技术有限公司
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from CN201610160797.0A external-priority patent/CN105675369B/zh
Priority claimed from CN201610798074.3A external-priority patent/CN106153436B/zh
Application filed by 广州深达生物制品技术有限公司 filed Critical 广州深达生物制品技术有限公司
Priority to CA3018633A priority Critical patent/CA3018633A1/en
Priority to JP2019500722A priority patent/JP2019510243A/ja
Priority to EP17769427.0A priority patent/EP3435064A4/en
Priority to US16/087,099 priority patent/US11221281B2/en
Publication of WO2017162150A1 publication Critical patent/WO2017162150A1/zh

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/44—Sample treatment involving radiation, e.g. heat
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • B01L7/02—Water baths; Sand baths; Air baths
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • B01L7/52—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
    • B01L7/525—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples with physical movement of samples between temperature zones
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • B01L7/54—Heating or cooling apparatus; Heat insulating devices using spatial temperature gradients
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/02—Devices for withdrawing samples
    • G01N1/10—Devices for withdrawing samples in the liquid or fluent state
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/30—Staining; Impregnating ; Fixation; Dehydration; Multistep processes for preparing samples of tissue, cell or nucleic acid material and the like for analysis
    • G01N1/31—Apparatus therefor
    • G01N1/312—Apparatus therefor for samples mounted on planar substrates
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/36—Embedding or analogous mounting of samples
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/38—Diluting, dispersing or mixing samples
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00029—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/14—Process control and prevention of errors
    • B01L2200/143—Quality control, feedback systems
    • B01L2200/147—Employing temperature sensors
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0406—Moving fluids with specific forces or mechanical means specific forces capillary forces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0694—Valves, specific forms thereof vents used to stop and induce flow, backpressure valves
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/08—Regulating or influencing the flow resistance
    • B01L2400/082—Active control of flow resistance, e.g. flow controllers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
    • B01L3/50855—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates using modular assemblies of strips or of individual wells
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L9/00—Supporting devices; Holding devices
    • B01L9/52—Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/38—Diluting, dispersing or mixing samples
    • G01N2001/386—Other diluting or mixing processes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00029—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides
    • G01N2035/00099—Characterised by type of test elements
    • G01N2035/00138—Slides
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N2035/00346—Heating or cooling arrangements
    • G01N2035/00356—Holding samples at elevated temperature (incubation)

Definitions

  • the invention belongs to the field of biological sample processing, and in particular relates to a device for processing a specimen specimen.
  • the specimens need to be heat treated in the middle of the specimen processing process, which is a necessary step to achieve the sensitivity and specificity of protein or gene detection. Heating is generally carried out at a temperature of 80-121 ° C for 3 to 60 minutes. The most common methods are cooking in a pressure cooker, general boiling, microwave cooking, hot water bath heating, etc. However, containers or carriers that are currently handled by conventional slide specimens are not heat resistant and do not have a heatable function. In the middle of the processing of the specimen specimen, the specimen specimen needs to be transferred to a heatable container, and then needs to be transferred to a normal temperature operating table, which increases the complexity of the operation flow and the operation error.
  • the invention realizes the heat treatment device in the process of carrying the specimen, and is used together with the related invention, can realize the requirements in the process of processing the specimen specimen and the various steps without heating, can be carried out in the same device, simplifying the slide
  • the processing steps of the specimen processing improve the efficiency and reliability of the specimen specimen processing.
  • a heat treatment device for detecting a specimen specimen which enables a large number of slides to be closely placed in a heatable container and configured with a liquid filling and draining device.
  • the steps required to realize and not require heating during the processing of the slide specimen can be performed in the same device, simplifying the operation steps of the specimen specimen processing, and improving the efficiency and reliability of the specimen specimen processing.
  • the object of the invention is achieved at least by one of the following technical solutions.
  • a heat treatment device for detecting a specimen specimen comprising a container, a base, a heater, a liquid discharge port, a liquid inlet, a controller and a thermocouple;
  • the heater is located above the base and below the container; the container is used to place the heating medium and more than one slide holder; the controller is used to control the start and stop of the heater, the heater is used to heat the medium in the container; the thermocouple is placed in the container, The thermocouple senses the temperature in the container in real time and transmits the sensing data to the controller;
  • the liquid inlet allows the heating medium or reagent stored in the outer container to be metered into the container as needed; the liquid discharge port allows the heating medium or liquid in the container to exit the container.
  • the heater disposed at the bottom of the container is heated by electric heating rods, heating wire heating, microwave heating, electromagnetic induction heating or heat medium circulation heating; the heater and the container are connected structures or separable structures.
  • liquid inlet and the liquid discharge port on the container are also respectively connected with a micro pump or a solenoid valve, and the controller controls the operation of the micro pump or the electromagnetic valve to control the liquid to be poured into or discharged from the container.
  • edge of the container is a right angle structure; the bottom of the container is a planar structure.
  • the heat treatment device for detecting a specimen specimen further comprises at least one slide holder, and both ends of the slide holder are hung on two sides of the container facing each other, so that the slide assembly in the slide holder a gap is left between the bottom end and the bottom of the container;
  • the slide holder is provided with a plurality of vertical or inclined V-shaped slots which are integrally formed vertically or obliquely, and a spring piece is fixedly disposed in each V-shaped slot a plurality of V-shaped sockets are closely arranged in a row
  • the carrier bracket comprises one or more columns of V-shaped slots; the shape of the upper end of the carrier assembly combined with the carrier and the cover plate and the V-shaped on the bracket
  • the mounting slots are matched so that the carrier assembly can be inserted into the V-shaped slot in the carrier bracket to form a plurality of closely arranged carrier assemblies;
  • the spring piece and the V-shaped slot of the carrier bracket are integrally connected or separately separated, and the spring piece is fixed or fixed in the V-shaped slot when the separation is independent; when the carrier assembly is inserted In the V-shaped slot, the surface of the cover presses against the spring piece, and the spring piece functions to clamp the slide piece and the slide cover.
  • a slide assembly is inserted in each of the V-shaped slots, and the plurality of slide assemblies are heated by a single controller at the same temperature in the same container; the slide assembly is inserted in the V-shaped slot.
  • Standing or tilting, the angle of the slide assembly to the vertical direction is 1 to 90 degrees.
  • the heating medium in the container may be heated to boiling, and the heat treatment temperature is controlled by using a heating medium having a fixed boiling point.
  • the slide assembly is composed of a slide piece and a cover plate;
  • the cover plate includes a capillary plane, a depth positioning surface, a width positioning block, a bottom positioning block, a groove side surface and a groove opening surface;
  • the capillary planes are mutually opposite each other
  • the two depth positioning surfaces are disposed above the two sides, and the capillary plane is parallel to the depth positioning surface; the portion of the carrier near the two side edges is in contact with the depth positioning surface, so that between the surface of the carrier and the capillary plane Forming a capillary slit;
  • one or more of the width positioning blocks are disposed on each of the depth positioning surfaces away from the capillary plane; the vertical distance between the width positioning blocks on the different depth positioning surfaces is matched with the width of the slide
  • the bottom positioning block is disposed at the bottom end of the depth positioning surface;
  • the groove opening surface is connected with the upper end of the capillary plane and forms an angle A1, and A1 is a plane angle of 1 to 175 degrees
  • the label slot When the label is attached to the carrier, the label slot provides Sufficient space for accommodating the thickness of the label so that the slide cover can be attached to the slide without being affected by the label on the slide; the outer side of the two groove sides is provided with a top strip for adding the side of the groove
  • the friction between the fingers; the vertical distance between the capillary plane and the depth locating surface is 0.01 ⁇ 0.5mm, so that the distance between the surface of the slide and the capillary plane is 0.01 ⁇ 0.5 after the slide cover and the slide are closely attached.
  • the width of the width positioning block is 0.1 to 1 mm above the depth positioning surface;
  • the bottom positioning block is an upward hook shape, and the bottom positioning block and the width positioning block together determine the relative relationship between the cover and the carrier after bonding Position and assist in maintaining a close fit between the cover and the slide.
  • one or more separate containers and corresponding independent heaters are provided for simultaneous heat treatment of downloaded specimens at different temperatures, different environments or different workflows.
  • the heating medium in the vessel can be simply heated to boiling, and the heat treatment temperature is controlled by selecting the boiling point of the corresponding heating medium to achieve uniformity, reliability and repeatability of the heat treatment.
  • the entire process of the slide specimen processing does not move at the same position.
  • the present invention has the following advantages and technical effects:
  • the whole process of the specimen specimen processing does not need to manually take or transfer the slide, reducing manual intervention and intervention, which can save time, simplify operation and reduce operation error.
  • slide assembly When the slide assembly is heat treated, a plurality of slide assemblies are controlled by a single heating controller in the same container to ensure uniformity of heat treatment.
  • the medium When the specimen specimen is heat-treated, the medium can be simply heated to boiling, and the heat treatment temperature is controlled by the boiling point of the heating medium to achieve uniformity of heat treatment, and has high reliability and repeatability.
  • the process of processing the specimen specimen does not present the possibility of the specimen being dried.
  • the V-shaped slot cooperates with the structure of the slide assembly, and the structure of the bracket device is simpler and more compact, so that the container can accommodate more slide components, and the finger can be used to clamp the top stripe on the side of the two slots, which is easy to use.
  • the slide assembly is inserted into the slot to avoid uneven force or the direction of the force being biased, which causes the slide to disengage the slide cover, ensuring the formation and accuracy of the capillary gap, and the operation is more convenient and quick.
  • the arrangement of the slide components can be more compact, further reducing the space and improving the processing efficiency.
  • Figure 1 is a schematic view of a heat treatment apparatus for detecting specimen specimens of the present invention.
  • Fig. 2 is a cross-sectional view showing a heat treatment apparatus for detecting a specimen specimen of the present invention.
  • FIG 3 is a perspective view of the heat treatment apparatus shown in Figure 1.
  • Figure 4 is a schematic illustration of a slide holder in the example.
  • Figure 5 is a schematic view of a slide carrier in which multiple rows of slots are provided in the example.
  • Figure 6 is a schematic view of the slide carrier assembly mounted on a slide holder of Figure 4.
  • Figure 7 is a schematic illustration of the cover of the slide assembly of the example.
  • Figure 8 is a schematic illustration of a slide assembly in an example.
  • Figure 9a is a front projection view of Figure 8.
  • Figure 9b is a side view of Figure 8.
  • Figure 9c is a partial enlarged view of Figure 8.
  • 10a and 10b are respectively a plan view and a cross-sectional view of a carrier holder in which a container of a heat treatment apparatus of the example suspends a plurality of rows of V-shaped slots.
  • a heat treatment device for detecting a specimen specimen includes a container 301, a base 302, a heater 303, a liquid discharge port 307, a liquid inlet 308, a controller 309, and a thermocouple 312;
  • the heater 303 is located above the base 302 and below the container 301; the container 301 is used to place the heating medium and more than one slide holder 602; the controller 309 is used to control the start and stop of the heater, and the heater is used to heat the medium in the container 301
  • the thermocouple 312 is placed in the container, and the thermocouple 312 senses the temperature in the container 301 in real time and transmits the sensing data to the controller 309.
  • the liquid inlet 308 allows the heating medium or reagent stored in the outer container to be metered into the container 301 as needed; the liquid discharge port 307 allows the heating medium or liquid in the container 301 to be discharged out of the container.
  • the liquid inlet 308 and the liquid discharge port 307 on the container are also respectively connected with a micro pump or a solenoid valve, and the controller controls the operation of the micro pump or the solenoid valve to control the liquid filling into or discharging from the container.
  • the drain port 307 is connected to the drain pump 310 for discharging liquid from the container as necessary; the liquid inlet port 308 is connected to the feed water pump 311 for pouring liquid into the container as necessary.
  • the apparatus further provides a heat treatment time (holding time) display module 314 for displaying the length of the heat treatment time; and a holding time adjustment key 315 for setting the length of the holding time.
  • the filling and discharging of the heating medium can also be carried out into or discharged from the container by the action of gravity by controlling the opening and closing of the solenoid valve.
  • the controller adopts a controller such as a PIC single chip microcomputer, a 51 single chip microcomputer or a PLC controller, and controls the powering on and off of the relay through the controller, thereby realizing the start and stop of the heating function, and realizing the opening and closing of the inlet port and the discharge port. control.
  • the heater 303 disposed at the bottom of the container adopts electric heating rod heating, electric heating wire heating, microwave heating, electromagnetic induction heating or heat medium circulation heating mode; the heater 303 and the container 301 are connected or separable. Structure.
  • the edge of the container is a right angle structure, and the right angle structure of the edge of the container facilitates the full use of the container to mount the slide holder 602.
  • the bottom of the container has a planar structure that facilitates draining of the liquid in the container.
  • the slide holder 602 is provided with a plurality of V-shaped slots 604 integrally formed, and a spring piece 603 is fixedly disposed in each V-shaped slot 604; a plurality of V-shaped slots Tightly arranged in a row, Figure 4 shows a slide holder 602 having a row of V-shaped slots, and Figure 5 shows a slide holder 602b having a plurality of rows of V-shaped slots. Multiple sets (multiple columns) of parallel slide holders (602 or 602b) can be suspended from the container.
  • the slide holder 602 is made of a heat-resistant material and can withstand the heat treatment process when the specimen is inspected.
  • the spring piece and the carrier holder are made of a heat resistant material, and the spring piece can also be made of a thin metal plate.
  • a slide assembly is inserted into each of the V-shaped slots 604.
  • the plurality of slide assemblies are heated in a single container 301 at a controlled temperature by a single controller, rather than each of the slide specimens being separately heated and independently temperature controlled.
  • the assembly of the carrier 101 and the slide cover 601 is inserted along the mounting slot 604 of the slide holder 602, and the surface of the slide cover 601 presses the plate spring 603 to generate spring pressure on the slide. 101 and the slide cover 601 are used to achieve a pressing action.
  • the slide assembly is composed of a slide 101 and a cover 601;
  • the cover includes a capillary plane 1, a depth positioning surface 2, a width positioning block 3, and a bottom positioning block 4.
  • the two depth positioning surfaces 2 are disposed above the mutually opposite side edges of the capillary plane 1, and the capillary plane 1 is parallel to the depth positioning surface;
  • the plane of the slide is close to The portions of the two side edges are in contact with the depth positioning surface 2 to form a capillary gap between the surface of the carrier sheet and the capillary plane 1; more than one of the widths of each of the depth positioning surfaces 2 away from the capillary plane 1 is provided.
  • the slot opening surface 7 is connected to the upper end of the capillary plane 1 and forms an angle A1, which is a plane angle of 1 to 175 degrees;
  • a slot side surface 6 is connected to each side of the slot opening surface 7; the slot opening surface 7 and the two slots
  • the side surface 6 and the plane of the slide piece together form a sampling tank which communicates with the capillary gap
  • the bottom of the capillary slit has a slit opening; the length of the slide cover is equal to or equal to the length of the slide, and the side of the groove side 6 that fits the plane of the slide, that is, the upper end of the two depth positioning surfaces 2 is provided with a label.
  • the label slot when the label is affixed to the carrier, the label slot provides sufficient space for accommodating the thickness of the label so that the slide cover can be attached to the slide without being affected by the label on the slide;
  • the outer side of the side surface 6 is provided with a top stripe 10 for increasing the friction between the side surface 6 of the groove and the finger;
  • the vertical distance between the capillary plane 1 and the depth positioning surface 2 is 0.01 to 0.5 mm, so that the slide cover and the carrier After the sheet is in close contact, a capillary slit having a spacing of 0.01 to 0.5 mm is formed between the surface of the carrier and the capillary plane 1;
  • the thickness of the width positioning block 3 is 0.1 to 1 mm higher than the depth positioning surface 2;
  • the bottom positioning block 4 is upward.
  • the hook-like, bottom locating block 4 together with the width locating block 3 determines the relative position of the cover after it is attached to the carrier and assists in maintaining a snug fit between the cover and the carrier.
  • the bottom of the capillary plane 1 is also provided with two flow guiding angles 11; a funnel-shaped flow guiding opening 5 is formed between the two guiding flow angles and allows the solution in the capillary plane to flow out from the flow guiding opening.
  • the sliced specimen is adhered to the surface of the slide in the capillary gap; when the reagent is applied to the sample introduction tank, the reagent enters the capillary gap from the sample introduction slot and covers the specimen due to gravity and capillary siphoning.
  • the reagent enters the capillary gap from the sample introduction slot and covers the specimen due to gravity and capillary siphoning.
  • All parts of this example are made of materials that can withstand more than 80oC without deformation or softening.
  • one or more separate vessels and corresponding independent heaters can be provided for simultaneous heat treatment of downloaded specimens at different temperatures, different environments, or different workflows.
  • the heating medium in the vessel 301 can be heated to boiling, and the heat treatment temperature is controlled by using a heating medium having a fixed boiling point to achieve uniformity of heat treatment, and has the characteristics of high reliability and repeatability.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Analytical Chemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Clinical Laboratory Science (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Engineering & Computer Science (AREA)
  • Hydrology & Water Resources (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Devices For Use In Laboratory Experiments (AREA)

Abstract

一种载片标本检测的热处理装置，主要包括容器(310)、底座（302）、加热器(303) 、排液口(307)、进液口(308)、控制器(309)和热电偶(312)。该装置与载片盖板和载片支架等装置一起使用时，可以使大量载片标本在同一装置内进行试剂加样、清洗、热处理、保温、脱水步骤，尤其如免疫组化、原位杂交以及其它载片标本蛋白检测、DNA核苷酸和基因检测等的多步骤操作，使载片标本的所有检测从始至终在同一个装置内进行，并保障所有载片标本从始至终得到试剂的完全覆盖、保障所有载片标本在均一的温度控制下进行热处理。简化了操作流程，提高了载片标本处理的可靠性和重复性。

Description

一种载片标本检测的热处理装置
技术领域
本发明属于生物样品处理领域，特别是涉及一种载片标本处理的装置。
背景技术
载片标本上的蛋白、病原体或基因检测（如免疫组织化学以及原为杂交基因检测等）整个过程需要几十个复杂的步骤，环境和人为操作各种因素严重影响到测试结果的准确性。简化操作流程、减少受环境影的因素是提高标本检测效率和准确性的当务之急。
通常，标本处理过程的中途，绝大部分标本需要加热处理，这是使蛋白或基因检测达到应有的灵敏度和专一性所必须的步骤。加热一般在80-121℃的温度下进行并维持3-60分钟。最常用的方法是高压锅烹煮、一般沸煮、微波炉烹煮、热水浴加热货烘烤等方法。然而，目前操作常用的载片标本处理的容器或载架都不耐热，也不具备可加热的功能。在载片标本处理的中途需要将载片标本转移到可加热的容器内进行，而后又需要转移到常温的操作台上，增加了操作流程的复杂性和操作误差。
本发明实现载片标本过程中的热处理装置，与相关的发明一起使用，可以实现载片标本处理过程中的需要和不需要加热的各个步骤，都可以在同一个装置内进行，简化了载片标本处理的操作步骤，提高载片标本处理的效率和可靠性。
发明内容
为了解决上述问题，提出了一种载片标本检测的热处理装置，能够使大批量的载片紧密放置在可加热容器内并配置灌液和排液装置， 实现载片标本处理过程中需要和不需要加热的各个步骤，都可以在同一个装置内进行，简化了载片标本处理的操作步骤，提高载片标本处理的效率和可靠性。
本发明的目的至少通过如下技术方案之一实现。
一种载片标本检测的热处理装置，包括容器、底座、加热器、排液口、进液口、控制器和热电偶；
加热器位于底座上方且位于容器下方；容器用于放置加热介质和一个以上的载片支架；控制器用于控制加热器启动与停止，加热器用于加热容器中的介质；热电偶安置在容器内，热电偶实时感应容器中的温度，并将感应数据传递给控制器；
进液口允许存储在外部容器中的加热介质或试剂在需要时定量加入容器中；排液口允许将容器中的加热介质或液体排出容器。
进一步地，所述设置在容器底部的加热器采用电热棒加热、电热丝加热、微波加热、电磁感应加热或热介质循环加热方式；所述加热器与容器为连体结构或可分离式结构。
进一步地，容器上的所述进液口和排液口还各自连接有微泵或电磁阀，控制器控制微泵或电磁阀的工作进而实现控制向容器中灌液或从容器中排液。
进一步地，容器边缘为直角结构；容器底部为平面结构。
进一步地，所述的一种载片标本检测的热处理装置还包括至少一个载片支架，载片支架的两端挂在容器相互正对的两侧边上，使载片支架中的载片组件底端与容器底部留有间隙；所述载片支架上设置有一体形成的竖直或倾斜的多个竖直或倾斜的V形安插槽，每个V形安插槽中固定设置弹簧片；多个V形安插槽紧密排成一列，所述载片支架包括一列或多列V形安插槽；由载片及盖板组合成的载片组件上端的外形与支架上的V形安插槽相匹配，使得载片组件能安插在载片支架上的V形安插槽里，形成多个紧密排列的载片组件；
弹簧片与载片支架的V形安插槽为一体连接结构或者独立分离设置，采用独立分离设置时弹簧片以嵌合或粘接方式固定在V形安插槽内；当载片组件安插在V形安插槽里，盖板的表面压住弹簧片，弹簧片起到夹紧载片与载片盖板的作用。
进一步地，每个V形安插槽中安插有载片组件，多个载片组件在同一个容器内由单一控制器控制温度下进行加热；载片组件在安插在V形安插槽是为竖立或倾斜，载片组件与竖直方向的角度为1~90度。
进一步地，载片组件热处理时，可以将容器内的加热介质加热至沸腾，通过采用固定沸点的加热介质而控制热处理温度。
进一步地，载片组件由载片和盖板组成；所述盖板包括毛细平面、深度定位面、宽度定位块、底部定位块、槽侧面和槽开口面；所述毛细平面的相互正对的两侧边上方设置有所述两个深度定位面，毛细平面与深度定位面平行；所述载片的平面靠近两侧边缘的部分与深度定位面贴合，使载片表面与毛细平面之间形成一个毛细缝隙；每个深度定位面上远离毛细平面的外侧边缘设有一个以上的所述宽度定位块；位于不同深度定位面上的宽度定位块之间的垂直距离与载片的宽度匹配以起到限位作用；底部定位块设置在深度定位面的底端；所述槽开口面与毛细平面的上端连接并形成夹角A1，A1为1~175度平面角；槽开口面两侧各连接有一个槽侧面；所述槽开口面及两个槽侧面与载片平面共同构成一个与所述毛细缝隙连通的加样槽，毛细缝隙底部具有缝隙口；载片盖板与载片的长度相当或相等，槽侧面上与载片平面贴合的一侧即所述两个深度定位面的上端均设有一个标签槽，当载片上贴有标签时，标签槽提供足够的空间用于容纳标签的厚度，使载片盖板能够与载片贴紧而不受载片上是否贴有标签的影响；两个槽侧面的外侧设有顶部条纹，用于增加槽侧面与手指之间的摩擦力；毛细平面与深度定位面之间的垂直距离为0.01~0.5mm，使载片盖板及载片贴紧之后载片表面与毛细平面之间形成一个间距为0.01~0.5mm的毛细缝隙；所述宽度定位块高出深度定位面的厚度为0.1~1mm；底部定位块为向上的钩状，底部定位块与宽度定位块一起确定盖板与载片贴合之后的相对位置并协助保持盖板和载片之间的紧密贴合。
进一步地，设置一个或多个独立的容器和相应的独立的加热器，用于同时进行不同温度、不同环境或不同工作流程下载片标本的热处理。
进一步优化地，热处理时，可简单地将容器内的加热介质加热至沸腾，通过选用相应加热介质的沸点控制热处理温度，达到热处理的均一性、可靠性和重复性。载片标本处理的全过程载片处在同一个位置上没有移动。
相对于现有技术，本发明具有以下优点和技术效果：
载片标本处理的全过程都无需人为拿取或转移载片，减少人工干预和介入，即可节省时间，简化操作又可减少操作误差。
载片组件热处理时，多个载片组件在同一个容器内由单一加热控制器控制下进行，确保热处理的均一性。
载片标本热处理时，可简单地加热介质至沸腾，通过加热介质的沸点控制热处理温度，达到热处理的均一性，且具有高可靠性和可重复性的特点。
载片标本处理的过程不会出现载片标本干枯的可能性。
V形安插槽与载片组件的结构配合，支架装置结构更加简单紧凑，使容器能容纳更多的载片组件，使用时只需用手指夹住两个槽侧面的顶部条纹部位，轻易将载片组件插入安插槽中，避免按压载片顶端时受力不均或受力方向有偏差导致载片脱开载片盖板，保障毛细缝隙的形成和精确性，操作更加简便快捷。另外，载片组件的排列可以更加紧密，进一步减少空间，提高处理效率。
附图说明
图1是本发明的一种载片标本检测的热处理装置示意图。
图2是本发明的一种载片标本检测的热处理装置剖析图。
图3是图1所示热处理装置的立体图。
图4是实例中一种载片支架的示意图。
图5是实例中设置多列安插槽的载片支架示意图。
图6是图4所示一种载片支架上安插了载片组件的示意图。
图7是实例中载片组件的盖板示意图。
图8为实例中载片组件示意图。
图9a是图8的正面投影视图。
图9b是图8的侧视图。
图9c是图8的局部放大图。
图10a、图10b分别为实例中热处理装置的容器悬挂多列V形安插槽的载片支架的俯视图和剖视图。
具体实施方式
面将结合具体实施例对本发明作进一步说明，但本发明的实施和保护不限于此。
如图1、图2，一种载片标本检测的热处理装置，包括容器301、底座302、加热器303、排液口307、进液口308、控制器309和热电偶312；
加热器303位于底座302上方且位于容器301下方；容器301用于放置加热介质和一个以上的载片支架602；控制器309用于控制加热器启动与停止，加热器用于加热容器301中的介质；热电偶312安置在容器内，热电偶312实时感应容器301中的温度，并将感应数据传递给控制器309。
进液口308允许存储在外部容器中的加热介质或试剂在需要时定量加入容器301中；排液口307允许将容器301中的加热介质或液体排出容器。容器上的所述进液口308和排液口307还各自连接有微泵或电磁阀，控制器控制微泵或电磁阀的工作进而实现控制向容器中灌液或从容器中排液。本实例中，排液口307连接排水泵310，用于必要时从容器中排出液体；进液口308连接进水泵311：用于必要时向容器里灌注液体。实例中，该装置还提供了热处理时间（保温时间）显示模块314，用于显示热处理时间的长度；保温时间调节键315，用于设置保温时间的长度。
作为实例，加热介质的灌入和排出也可以通过控制电磁阀的开闭，利用重力的作用向容器内灌入或从容器内排出。所述控制器采用PIC单片机、51单片机或者PLC控制器等控制器，通过控制器对继电器的通电和断电进行控制，从而实现对加热功能的启动与停止、实现对进入口和排出口开合的控制。
作为实例，所述设置在容器底部的加热器303采用电热棒加热、电热丝加热、微波加热、电磁感应加热或热介质循环加热方式；所述加热器303与容器301为连体结构或可分离式结构。
如图1或图3，容器边缘为直角结构，容器边缘的直角结构有利于充分利用容器摆放载片支架602。容器底部为平面结构，有利于排尽容器中的液体。
如图4、图5，所述载片支架602上设置有一体形成的多个V形安插槽604，每个V形安插槽604中固定设置弹簧片603；多个V形安插槽紧密排成一列，图4所示为具有一列V形安插槽的载片支架602，图5所示为具有多列V形安插槽的载片支架602b。容器上可悬挂放置多组（多列）平行的载片支架（602或602b）。载片支架602由耐热材料制做，能承受载片标本检测时的热处理过程。弹簧片与载片支架采用耐热材料，弹簧片也可以采用金属薄板制作。每个V形安插槽604中安插有载片组件，多个载片组件在同一个容器301内由单一控制器控制温度下进行加热，而不是每个载片标本分开加热、独自温度控制。载片101和载片盖板601配合而成的组合件，沿着载片支架602上的安插槽604插入，载片盖板601的表面压制板型弹簧603，产生弹簧压力施加在载片101和载片盖板601上以实现压紧作用。
如图7、图8、图9a~图9c，载片组件由载片101和盖板601组成；所述盖板包括毛细平面1、深度定位面2、宽度定位块3、底部定位块4、槽侧面6和槽开口面7；所述毛细平面1的相互正对的两侧边上方设置有所述两个深度定位面2，毛细平面1与深度定位面平行；所述载片的平面靠近两侧边缘的部分与深度定位面2贴合，使载片表面与毛细平面1之间形成一个毛细缝隙；每个深度定位面2上远离毛细平面1的外侧边缘设有一个以上的所述宽度定位块3；位于不同深度定位面2上的宽度定位块3之间的垂直距离与载片的宽度匹配以起到限位作用；底部定位块4设置在深度定位面2的底端；所述槽开口面7与毛细平面1的上端连接并形成夹角A1，A1为1~175度平面角；槽开口面7两侧各连接有一个槽侧面6；所述槽开口面7及两个槽侧面6与载片平面共同构成一个与所述毛细缝隙连通的加样槽，毛细缝隙底部具有缝隙口；载片盖板与载片的长度相当或相等，槽侧面6上与载片平面贴合的一侧即所述两个深度定位面2的上端均设有一个标签槽9，当载片上贴有标签时，标签槽提供足够的空间用于容纳标签的厚度，使载片盖板能够与载片贴紧而不受载片上是否贴有标签的影响；两个槽侧面6的外侧设有顶部条纹10，用于增加槽侧面6与手指之间的摩擦力；毛细平面1与深度定位面2之间的垂直距离为0.01~0.5mm，使载片盖板及载片贴紧之后载片表面与毛细平面1之间形成一个间距为0.01~0.5mm的毛细缝隙；所述宽度定位块3高出深度定位面2的厚度为0.1~1mm；底部定位块4为向上的钩状，底部定位块4与宽度定位块3一起确定盖板与载片贴合之后的相对位置并协助保持盖板和载片之间的紧密贴合。所述毛细平面1上的底部还设置两个导流角11；所述的两个导流角之间形成一个漏斗式的导流口5并允许毛细平面中的溶液从导流口流出。
切片标本黏贴在载片上并处于毛细缝隙中的载片表面上；试剂加到加样槽时，由于重力和毛细虹吸作用，试剂从加样槽进入毛细缝隙，覆盖在标本上。使用时只需用手指夹住两个槽侧面的顶部条纹部位，轻易将载片组件插入安插槽中，避免按压载片顶端时受力不均导致载片脱开载片盖板，保障毛细缝隙的形成和精确性，操作更加简便快捷。另外，载片组件的排列可以更加紧密，进一步减少空间，提高处理效率。
本实例所有部件均采用能够耐受80oC 以上而不变形或软化的材料制做。
作为实例，可以设置一个或多个独立的容器和相应的独立的加热器，用于同时进行不同温度、不同环境或不同工作流程下载片标本的热处理。载片组件热处理时，可以将容器301内的加热介质加热至沸腾，通过采用固定沸点的加热介质而控制热处理温度，达到热处理的均一性，且具有可靠性高和可重复性的特点。
根据上述说明书的揭示和教导，本发明所属领域的技术人员还可以对上述方式进行变更和修改。因此，本发明并不局限于上面揭示和描述的具体方式，对本发明的一些修改和变更也应当落入本发明的权利要求的保护范围内。

Claims (10)

  1. 一种载片标本检测的热处理装置，其特征在于包括容器（301）、底座（302）、加热器（303）、排液口（307）、进液口（308）、控制器（309）和热电偶（312）；
    加热器（303）位于底座（302）上方且位于容器（301）下方；容器（301）用于放置加热介质和一个以上的载片支架（602）；控制器（309）用于控制加热器启动与停止，加热器用于加热容器（301）中的介质；热电偶（312）安置在容器内，热电偶（312）实时感应容器(301)中的温度，并将感应数据传递给控制器（309）；
    进液口（308）允许存储在外部容器中的加热介质或试剂在需要时定量加入容器（301）中；排液口（307）允许将容器（301）中的加热介质或液体排出容器。
  2. 根据权利要求1所述的一种载片标本检测的热处理装置，其特征在于：所述设置在容器底部的加热器（303）采用电热棒加热、电热丝加热、微波加热、电磁感应加热或热介质循环加热方式；所述加热器（303）与容器（301）为连体结构或可分离式结构。
  3. 根据权利要求1所述的一种载片标本检测的热处理装置，其特征在于容器上的所述进液口（308）和排液口（307）还各自连接有微泵或电磁阀，控制器控制微泵或电磁阀的工作进而实现控制向容器中灌液或从容器中排液。
  4. 根据权利要求1所述的一种载片标本检测的热处理装置，其特征在于：容器边缘为直角结构。
  5. 根据权利要求1所述的一种载片标本检测的热处理装置，其特征在于：容器底部为平面结构。
  6. 根据权利要求1所述的一种载片标本检测的热处理装置，其特征在于：还包括至少一个载片支架（602），载片支架（602）的两端挂在容器相互正对的两侧边上，使载片支架（602）中的载片组件底端与容器底部留有间隙；所述载片支架（602）上设置有一体形成的竖直或倾斜的多个V形安插槽（604），每个V形安插槽（604）中固定设置弹簧片（603）；多个V形安插槽紧密排成一列，所述载片支架包括一列或多列V形安插槽；由载片（101）及盖板（601）组合成的载片组件上端的外形与支架上的V形安插槽（604）相匹配，使得载片组件能安插在载片支架（602）上的V形安插槽（603）里，形成多个紧密排列的载片组件；
    弹簧片（603）与载片支架的V形安插槽（604）为一体连接结构或者独立分离设置，采用独立分离设置时弹簧片以嵌合或粘接方式固定在V形安插槽（604）内；当载片组件安插在V形安插槽（604）里，盖板（601）的表面压住弹簧片（603），弹簧片起到夹紧载片（101）与载片盖板（601）的作用。
  7. 根据权利要求6所述的一种载片标本检测的热处理装置，其特征在于：每个V形安插槽（604）中安插有载片组件，多个载片组件在同一个容器（301）内由单一控制器控制温度下进行加热。
  8. 根据权利要求7所述的一种载片标本检测的热处理装置，其特征在于：载片组热处理时，可以将容器（301）内的加热介质加热至沸腾，通过采用固定沸点的加热介质而控制热处理温度。
  9. 根据权利要求7所述的一种载片标本检测的热处理装置，其特征在于：载片组件由载片（101）和盖板（601）组成；所述盖板包括毛细平面（1）、深度定位面（2）、宽度定位块（3）、底部定位块（4）、槽侧面（6）和槽开口面（7）；所述毛细平面（1）的相互正对的两侧边上方设置有所述两个深度定位面（2），毛细平面（1）与深度定位面平行；所述载片的平面靠近两侧边缘的部分与深度定位面（2）贴合，使载片表面与毛细平面（1）之间形成一个毛细缝隙；每个深度定位面（2）上远离毛细平面（1）的外侧边缘设有一个以上的所述宽度定位块（3）；位于不同深度定位面（2）上的宽度定位块（3）之间的垂直距离与载片的宽度匹配以起到限位作用；底部定位块（4）设置在深度定位面（2）的底端；所述槽开口面（7）与毛细平面（1）的上端连接并形成夹角A1，A1为1~175度平面角；槽开口面（7）两侧各连接有一个槽侧面（6）；所述槽开口面（7）及两个槽侧面（6）与载片平面共同构成一个与所述毛细缝隙连通的加样槽，毛细缝隙底部具有缝隙口；载片盖板与载片的长度相当或相等，槽侧面（6）上与载片平面贴合的一侧即所述两个深度定位面（2）的上端均设有一个标签槽（9），当载片上贴有标签时，标签槽提供足够的空间用于容纳标签的厚度，使载片盖板能够与载片贴紧而不受载片上是否贴有标签的影响；两个槽侧面（6）的外侧设有顶部条纹（10），用于增加槽侧面（6）与手指之间的摩擦力；毛细平面（1）与深度定位面（2）之间的垂直距离为0.01~0.5mm，使载片盖板及载片贴紧之后载片表面与毛细平面（1）之间形成一个间距为0.01~0.5mm的毛细缝隙；所述宽度定位块（3）高出深度定位面（2）的厚度为0.1~1mm；底部定位块（4）为向上的钩状，底部定位块（4）与宽度定位块（3）一起确定盖板与载片贴合之后的相对位置并协助保持盖板和载片之间的紧密贴合。
  10. 根据权利要求1~9任一项所述的一种载片标本检测的热处理器装置，其特征在于：设置一个或多个独立的容器和相应的独立的加热器，用于同时进行不同温度、不同环境或不同工作流程下载片标本的热处理。
PCT/CN2017/077572 2016-03-21 2017-03-21 一种载片标本检测的热处理装置 WO2017162150A1 (zh)

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