CN112300911A

CN112300911A - Nucleic acid detector and nucleic acid detection method

Info

Publication number: CN112300911A
Application number: CN202011165266.3A
Authority: CN
Inventors: 陈华云; 杨迎宾; 邹天桥; 薛儒冰; 肖湘文; 刘淑园; 吕婧; 曾烨
Original assignee: Guangzhou Heas Biotech Co ltd
Current assignee: Guangzhou Heas Biotech Co ltd
Priority date: 2020-10-27
Filing date: 2020-10-27
Publication date: 2021-02-02
Also published as: WO2022088477A1

Abstract

The invention belongs to the technical field of biological detection, and particularly discloses a nucleic acid detector and a nucleic acid detection method. The nucleic acid detecting instrument includes: a mounting frame; the reagent plate is provided with a nucleic acid amplification tube, a hybridization groove, a reaction tube and a reagent tube for storing and extracting reagents; a cover plate assembly capable of moving in a direction toward or away from the nucleic acid amplification tube to close or open the nozzle of the nucleic acid amplification tube; the heat treatment unit is used for heating or cooling the liquid on the reagent plate; the liquid transfer device is used for sucking and transferring liquid on the reagent plate; the oscillation unit is used for driving the reagent plate to oscillate back and forth along the horizontal direction; the magnetic attraction component is used for attracting and releasing magnetic beads in reaction liquid on the reagent plate. The nucleic acid detection method adopts the nucleic acid detector to detect nucleic acid. The nucleic acid detector and the nucleic acid detection method provided by the invention can improve the efficiency of nucleic acid detection.

Description

Nucleic acid detector and nucleic acid detection method

Technical Field

The invention relates to the technical field of biological detection, in particular to a nucleic acid detector and a nucleic acid detection method.

Background

The nucleic acid hybridization technique is that specific probes are respectively fixed on a solid phase material, and then a specific amplification product generated by nucleic acid amplification reaction is hybridized with the specific probes, so that a sample to be detected is combined with the probes with homologous sequences, and because the sample to be detected has biotin or fluorescein or digoxin and other markers, the biotin or fluorescein or digoxin and other markers are combined on the probe point of the sample to be detected, and then a hybridization signal can be displayed through corresponding chemiluminescence reaction or fluorescence excitation. The detection reaction can detect various target sequences by one-time hybridization reaction, has the characteristics of rapidness, simplicity, convenience, high sensitivity and strong specificity, and particularly has unique advantages in the aspects of genotyping, gene mutation detection, pathogen detection and the like.

Molecular diagnosis of biological samples based on nucleic acid hybridization techniques requires steps from sample pretreatment, sample nucleic acid extraction and purification, nucleic acid amplification, molecular hybridization, and the like, from the collection of clinical samples to the detection of results by hybridization. The whole experiment process comprises three steps of sample nucleic acid acquisition, sample nucleic acid amplification and replication, sample nucleic acid detection and analysis and the like, and the three steps are complicated in storage process, long in test time, high in technical requirements on operators and high in requirements on experimental equipment and facilities; meanwhile, in the experimental process, the possibility of sample cross contamination, reagent cross contamination, amplification product cross contamination and the like exists, the biological sample also has the possible biological safety hazard to experimental operators, and the application of the molecular hybridization technology in the aspect of nucleic acid detection is greatly limited by the factors.

At present, based on traditional solutions, instruments and devices for nucleic acid extraction and purification, nucleic acid amplification, nucleic acid molecule hybridization and the like, which are commercially applied to diagnosis, are separated, such as a sample preparation instrument and a nucleic acid extraction instrument for extracting nucleic acid; a PCR instrument for amplification or other nucleic acid amplification instruments; an automated hybridization instrument for hybridization, and the like. The specific process of completing the whole experiment includes, but is not limited to, manually adding the sample into a full-automatic nucleic acid extractor or fully manually extracting, after extracting and purifying the biological sample by using the full-automatic nucleic acid extractor or fully manually, manually transferring the purified nucleic acid solution to a nucleic acid amplification instrument, amplifying the extracted nucleic acid by using the nucleic acid amplification instrument, and then adding the amplified product into a full-automatic hybridization instrument for final hybridization analysis, wherein the non-macroscopic chemiluminescence method also needs to be equipped with a fluorescence scanner and the like. The whole experiment is carried out manually or linked, or extraction and amplification, molecular hybridization and the like are respectively realized by different instruments. This leads to the following problems:

1. the whole nucleic acid detection process needs professional experimenters with extremely high quality to follow the whole process, so that the labor cost and the probability of errors possibly caused by human are increased; meanwhile, when possible high-infectivity samples are processed, the biological safety threat is caused to the life safety of experimenters and the whole experimental environment;

2. the whole nucleic acid detection process is carried out in stages, manual intervention is needed, the uncontrollable property and uncertainty of the test are increased, meanwhile, the test time is long, and the detection efficiency is low or limited;

3. the whole nucleic acid detection process needs more than 10 kinds of various instruments and equipment such as a high-speed centrifuge, a water bath, a pipettor, a nucleic acid extraction and purification instrument, a reagent subpackaging instrument, a nucleic acid amplification instrument, a hybridization instrument, a scanner and the like, and more than 15 kinds of various matched consumables and the like; meanwhile, in order to meet the detection requirement, at least 30 different solutions and the like need to be prepared, and the preparation and preparation of the whole reagent consumable instrument are very complicated;

4. the whole nucleic acid detection process needs manual transfer of samples, various intermediate solutions and the like, the operation environment is relatively open, the risk of mutual pollution among the samples is increased, and the risk of mutual pollution among the solutions is also increased, so that the whole nucleic acid detection has extremely high requirements on the environment; meanwhile, the prepared instruments are expensive in material consumption and are not suitable for large-area popularization and application.

Disclosure of Invention

An object of the present invention is to provide a nucleic acid detecting apparatus, which can improve the efficiency of nucleic acid detection and reduce the cost of nucleic acid detection.

Another object of the present invention is to provide a method for detecting nucleic acid, which can improve the efficiency of nucleic acid detection and reduce the cost of nucleic acid detection.

In order to achieve the purpose, the invention adopts the following technical scheme:

a nucleic acid detecting instrument, comprising:

a mounting frame;

the reagent plate is provided with a nucleic acid amplification tube, a hybridization groove, a reaction tube and a reagent tube for storing and extracting reagents;

a cover plate assembly disposed on the mounting frame and capable of moving in a direction toward or away from the nucleic acid amplification tube to close or open a nozzle of the nucleic acid amplification tube;

the heat treatment unit is arranged on the mounting rack and is used for heating or cooling the liquid on the reagent plate;

the liquid transfer device is arranged on the mounting rack and is used for sucking and transferring liquid on the reagent plate;

the oscillating unit is arranged on the mounting frame and is relatively fixed with the reagent plate, and the oscillating unit is used for driving the reagent plate to oscillate back and forth along the horizontal direction;

the magnetic component is arranged on the mounting rack and can move in the direction towards or away from the reagent plate, and the magnetic component is used for attracting and releasing the reaction liquid on the reagent plate.

As a preferred technical scheme of a nucleic acid detector, the reagent board extends along the X direction and sets up, the reagent board is provided with a plurality ofly along the Y direction side by side, the apron subassembly sets up and is in a plurality of the reagent board is followed one side of X direction, the subassembly setting is inhaled to magnetism is in a plurality of the reagent board is followed the opposite side of X direction.

As a preferred embodiment of the nucleic acid detecting apparatus, the cover member includes:

a cap seal assembly including a cap seal located above the nucleic acid amplification tube, the cap seal being made of an elastic material, the cap seal being for sealing a nozzle of the nucleic acid amplification tube;

and the cover plate driving assembly is connected with the cover sealing assembly and is used for driving the cover sealing assembly to move in a translation mode or rotate so as to enable the cover sealing piece to seal or open the nozzle of the nucleic acid amplification tube.

As a preferred embodiment of the nucleic acid detecting apparatus, the nucleic acid detecting apparatus includes an oscillation heating unit including the heat treatment unit, the oscillation unit, and a heat insulating unit connected between the heat treatment unit and the oscillation unit, and the reagent plate is disposed above the heat treatment unit and fixed with respect to the heat treatment unit.

In a preferred embodiment of the nucleic acid detecting apparatus, the heat treatment unit includes a plurality of heating units arranged in parallel and at intervals in the X direction, the plurality of heating units are respectively disposed below the nucleic acid amplification tube, the hybridization chamber, the reaction tube, and the reagent tube, and each of the heating units extends in the Y direction.

As a preferred technical solution of a nucleic acid detecting apparatus, the heating unit includes a nucleic acid amplification tube heating block located below the nucleic acid amplification tube, the heat treatment unit further includes a cooling unit and a heat dissipation unit, the heat dissipation unit is located at one side of the nucleic acid amplification tube heating block and extends along the Y direction, and the cooling unit is located between the heat dissipation unit and the nucleic acid amplification tube heating block.

As a preferred technical scheme of a nucleic acid detector, the heat insulation unit comprises a plurality of heat insulation subunits arranged at intervals along the X direction, the heat insulation subunits correspond to the heating units one by one, the heating units are detachably connected above the heat insulation subunits, and each heat insulation subunit is made of a heat insulation material.

As a preferred technical scheme of a nucleic acid detector, the magnetism subassembly of inhaling includes:

the magnetic bar assembly comprises a plurality of vertically arranged magnetic bars, and the magnetic bars are arranged side by side along the Y direction;

and the magnetic bar driving assembly is connected with the magnetic bar assembly and is used for driving the magnetic bar assembly to move along the vertical direction.

As a preferred technical scheme of the nucleic acid detector, the magnetic rod assembly further comprises a mounting strip arranged along the Y direction, a mounting hole is formed in the mounting strip, and the lower end of the magnetic rod is inserted into the mounting hole in an interference manner;

the mounting strip is provided with a through hole in a penetrating mode in the vertical direction, one end of the through hole penetrates through the side wall of the mounting strip, the other end of the through hole is communicated with the mounting hole, the width of the through hole is smaller than the aperture of the mounting hole, and the through hole and the mounting hole are arranged in a one-to-one correspondence mode.

As a preferable technical solution of a nucleic acid detecting apparatus, a reagent bottle storage area is provided in the nucleic acid detecting apparatus, a reagent bottle carrying a reagent is stored in the reagent bottle storage area, and the liquid transfer device includes:

the first pipetting mechanism can horizontally move and vertically lift relative to the mounting rack and is used for pumping the liquid in the reagent bottle;

and the second pipetting mechanism can horizontally move and vertically lift relative to the mounting rack and is used for sucking and transferring the liquid on the reagent plate.

As a preferred technical scheme of the nucleic acid detecting instrument, the second liquid-moving mechanism comprises a suction head taking and placing unit, the suction head taking and placing unit comprises a suction head seat, a suction head loop bar connected to the suction head seat, a suction head nozzle inserted at the lower end of the suction head loop bar and a suction head needle penetrating the suction head loop bar and having a lower end hermetically inserted with the suction head nozzle, and the second liquid-moving mechanism can drive the suction head taking and placing unit to move horizontally and vertically;

the liquid-transfering device also comprises an injection pump, and the upper end of the suction head needle is connected with the injection pump through a blowing suction pipe.

As a preferred technical solution of a nucleic acid detecting apparatus, the first liquid-transferring mechanism includes at least two first reagent needles, and the first liquid-transferring mechanism can drive the first reagent needles to move horizontally and vertically;

the second pipetting mechanism comprises at least two reagent needle bundles, each reagent needle bundle comprising at least two second reagent needles;

the liquid transfer device further comprises a liquid pump set, the liquid pump set comprises a plurality of pairs of reagent liquid inlets and reagent liquid outlets, each first reagent needle is communicated with one reagent liquid inlet through a liquid inlet pipe, each reagent liquid outlet is communicated with one end of a main liquid outlet pipe, one end of each main liquid outlet pipe is communicated with one end of a plurality of branch liquid outlet pipes, the other ends of the branch liquid outlet pipes are communicated with one of the at least two reagent needle bundles, and the number of the branch liquid outlet pipes communicated with the main liquid outlet pipes is the same as that of the reagent needle bundles.

In a preferred embodiment of the nucleic acid detecting apparatus, the second reagent needle includes a main body portion and a guide portion connected to a lower end of the main body portion, the main body portion and the guide portion are integrally formed, an upper end of the guide portion is connected to the main body portion, a lower end of the guide portion extends obliquely downward, and the extending directions of the guide portions of the plurality of second reagent needles located in the same reagent needle bundle are different.

As a preferred technical scheme of nucleic acid detector, the second moves liquid mechanism still includes the waste liquid needle, the vertical setting of waste liquid needle, the second moves liquid mechanism can drive the waste liquid needle is followed Y direction and vertical direction motion, liquid pump group includes waste liquid import and waste liquid export, the waste liquid import with the waste liquid needle advances the pipe intercommunication through the waste liquid, the waste liquid export passes through waste liquid exit tube intercommunication waste liquid bottle.

As a preferred technical scheme of the nucleic acid detector, the nucleic acid detector further comprises a housing, the mounting frame, the reagent plate, the cover plate assembly, the heat treatment unit, the liquid-transferring device, the oscillation unit and the magnetic attraction assembly are all arranged inside the housing, an opening is formed in the housing, a door body used for closing or opening the opening is arranged at the opening, and the reagent plate can enter and exit the housing through the opening; an air draft filtering system and/or a sterilization and disinfection system are/is arranged inside the shell.

As an optimal technical scheme of a nucleic acid detecting instrument, nucleic acid detecting instrument still includes the consumptive material panel, be provided with a plurality of reagent board mouths side by side along the Y direction on the consumptive material panel, reagent board mouth extends along the X direction, the reagent board is including bearing the mainboard, nucleic acid amplification pipe hybridization groove the reaction tube reaches the reagent pipe all sets up bear on the mainboard, bear the lower surface of mainboard set up with on the consumptive material panel, just nucleic acid amplification pipe hybridization groove the reaction tube reaches the reagent pipe all stretches into in the reagent board mouth.

A nucleic acid detecting method applied to the nucleic acid detecting apparatus as described above, the nucleic acid detecting method comprising:

a pre-detection treatment, comprising the steps of: opening a cap of the nucleic acid amplification tube; the cover plate component closes the nozzle of the nucleic acid amplification tube;

nucleic acid extraction and purification, which is performed based on a magnetic bead method, and which includes: adding a sample into the reagent tube containing the proteinase K and the magnetic beads by the liquid transfer device, and uniformly mixing; the liquid transfer device sucks the mixed liquid of the uniformly mixed protease K, the magnetic beads and the sample liquid to a reaction tube containing a magnetic bead binding solution; the heat treatment unit regulates and controls the temperature condition required by the reaction of the reaction tube so as to crack cells and release nucleic acid; after releasing nucleic acid, the magnetic suction component moves back and forth along the direction close to or far away from the reagent plate and is matched with liquid extraction and transfer of the liquid transfer device to realize adsorption, washing and elution of nucleic acid on magnetic beads so as to obtain purified nucleic acid;

a nucleic acid amplification reaction comprising: the cover plate component moves to open the pipe orifice of the nucleic acid amplification pipe; pipetting a certain amount of nucleic acid into the nucleic acid amplification tube by using a pipetting device; the cover plate component moves to close the pipe orifice of the nucleic acid amplification pipe; starting a nucleic acid amplification program to perform a nucleic acid amplification reaction, during which temperature conditions required for the nucleic acid amplification reaction are controlled by the heat treatment unit;

a hybridization reaction comprising: moving the cover plate assembly to open the nozzle of the nucleic acid amplification tube; the pipetting device pumps the amplification solution in the nucleic acid amplification tube into the hybridization tank; and the pipetting device sequentially pumps different hybridization solutions into the hybridization tank, and during the period, the heat treatment module regulates and controls the temperature required by the reaction, and the oscillation unit drives the reagent plate to horizontally oscillate back and forth so as to realize the specific binding, washing and color development of the amplification product and the probes on the hybridization membrane.

The invention has the beneficial effects that:

the nucleic acid detector provided by the invention can concentrate the extraction and purification of biological sample nucleic acid, nucleic acid amplification and molecular hybridization detection on one instrument, and an operator can complete the whole detection process within 3.5-6 h only by simple preparation actions, so that the result is obtained, and the detection efficiency is high. Moreover, because the manual participation in the detection process is reduced, the pollution in the detection process can be reduced, and the detection precision is improved; meanwhile, the requirement of special instruments for nucleic acid detection can be reduced, and the nucleic acid detection cost is reduced.

According to the nucleic acid detection method provided by the invention, the nucleic acid detection is carried out by adopting the nucleic acid detector, so that the nucleic acid detection efficiency can be improved, the pollution occurrence probability in the nucleic acid detection can be reduced, and the nucleic acid detection cost can be reduced.

Drawings

FIG. 1 is a schematic structural diagram of a nucleic acid detecting apparatus according to an embodiment of the present invention;

FIG. 2 is a schematic diagram illustrating an internal structure of a nucleic acid detecting apparatus according to an embodiment of the present invention;

FIG. 3 is a schematic view of a disassembled structure of the nucleic acid detecting apparatus according to one embodiment of the present invention;

fig. 4 is a schematic diagram of a disassembled structure of the housing according to the first embodiment of the present invention;

FIG. 5 is a schematic structural diagram of a reagent plate according to a first embodiment of the present invention;

FIG. 6 is a schematic structural diagram of an oscillating heating element and a reagent plate according to an embodiment of the present invention;

FIG. 7 is a schematic view of an oscillating heating element according to an embodiment of the present invention from a perspective;

FIG. 8 is a partial enlarged view taken at I in FIG. 7;

fig. 9 is a schematic diagram illustrating a disassembled structure of an oscillating heating assembly according to an embodiment of the present invention;

FIG. 10 is a schematic view of a cover plate assembly according to an embodiment of the present invention from a perspective;

FIG. 11 is a schematic view of a cover plate assembly from another perspective according to an embodiment of the present invention;

fig. 12 is a schematic view of a disassembled structure of a cover plate assembly according to an embodiment of the present invention;

fig. 13 is a schematic structural view of a magnetic attraction assembly according to an embodiment of the present invention at a viewing angle;

fig. 14 is a schematic structural view of a magnetic attraction assembly according to another view angle;

fig. 15 is a schematic view of a disassembled structure of a magnetic assembly according to a first embodiment of the present invention;

FIG. 16 is an enlarged view of a portion of FIG. 15 taken at J;

fig. 17 is a schematic structural diagram of a first pipetting mechanism provided in the first embodiment of the invention at a viewing angle;

fig. 18 is a schematic structural diagram of the first pipetting mechanism provided in the first embodiment of the invention from another perspective;

fig. 19 is a schematic diagram illustrating a disassembled structure of the first pipetting mechanism according to the first embodiment of the present invention;

FIG. 20 is a schematic structural diagram of a second pipetting mechanism provided in the first embodiment of the invention from a viewing angle;

FIG. 21 is a schematic structural diagram of a second pipetting mechanism provided in the first embodiment of the invention from another perspective;

fig. 22 is a schematic view of a second pipetting mechanism according to an embodiment of the invention;

FIG. 23 is a schematic view of the pipeline connection of the suction head pipeline assembly, the syringe pump and the suction head pick-up and place unit according to an embodiment of the present invention

FIG. 24 is a schematic view of the connection between the liquid pump and the reagent needle tube assembly according to one embodiment of the present invention

The figures are labeled as follows:

1. a housing; 11. a main housing; 12. a first front door; 13. a second front door; 131. an installation port; 14. a rear door; 15. a frame; 16. a waste liquid collecting tank;

2. a mounting frame; 21. a base plate; 22. a support frame; 221. a cross beam; 222. erecting a beam; 23. a support leg;

3. oscillating the heating assembly; 31. a heat treatment unit; 311. a nucleic acid amplification tube heating block; 312. a reaction tube heating block; 313. an extraction reagent heating block; 314. heating plate for hybridization tank; 315. heating the film; 316. a heat dissipation unit; 3161. a heat sink; 31611. a vertical plate portion; 31612. a lateral plate portion; 31613. a fin portion; 3162. a heat radiation fan; 317. a refrigeration unit; 319. a tube insertion hole; 3110. a weight reduction groove; 32. an oscillation unit; 321. a support plate; 322. an X-direction guide assembly; 3221. an X-direction guide rail; 3222. an X-direction sliding block; 323. a limiting block; 324. fixing a bracket; 33. a heat insulation unit; 331. a heat insulation block; 332. a heat insulating column; 333. a heat insulation support plate; 334. a thermally insulating support; 335. a heat insulation plate;

4. a reagent plate; 41. carrying a main board; 411. amplifying the hole sites; 412. a hybridization tank; 413. a bayonet; 414. a suction head cavity; 415. a waste liquid tank; 42. a reagent tube; 43. a reaction tube; 44. a sample tube; 45. a suction head pipe;

5. a cover plate assembly; 51. a cover seal assembly; 511. a top cover plate; 512. a vertical connecting plate; 513. a transverse connecting plate; 5131. a first horizontal plate portion; 5132. a second horizontal plate portion; 5133. a light axis aperture; 514. a cover seal; 52. a cover plate drive assembly; 521. a cover plate motor; 522. a cover plate screw rod; 523. a cover plate nut seat; 53. a cover plate motor base; 531. mounting a plate; 5311. a plate penetrating port; 532. a mounting seat; 533. a motor support plate; 54. a cover plate guide assembly; 541. a light axis seat; 542. an optical axis; 543. a linear bearing;

6. a magnetic component; 61. a magnetic bar assembly; 611. a magnetic bar; 612. mounting a bar; 6121. mounting holes; 6122. perforating; 6123. a positioning part; 613. installing a transverse plate; 6131. positioning a groove; 62. a magnetic bar drive assembly; 63. the magnetic attraction guide component; 64. a magnetic motor base;

7. a first pipetting mechanism; 71. a first reagent needle unit; 711. a first reagent needle; 712. a first reagent needle holder; 72. a first horizontal displacement unit; 721. a first horizontal drive assembly; 722. a connecting member; 723. a motor fixing plate; 73. a first vertical displacement unit; 731. an adapter plate; 732. a first vertical drive assembly; 74. a first horizontal guide assembly; 75. a first vertical guide assembly; 76. a buffer block; 77. a guide rail plate;

8. a second pipetting mechanism; 81. a second reagent needle unit; 811. a needle frame; 8111. a needle holder; 8112. a support bar; 8113. a needle mount; 812. a waste liquid needle; 813. a reagent needle bundle; 8131. a second reagent needle; 81311. a main body portion; 81312. a guide portion; 8132. a needle bundle cannula; 82. a second vertical displacement unit; 83. a suction head picking and placing unit; 831. a suction head seat; 832. a sucker sleeve rod; 833. a suction needle; 834. a suction nozzle; 84. a third vertical displacement unit; 85. fixing the vertical plate; 851. a door frame portion; 852. a floor section; 86. fixing the transverse plate; 87. withdrawing the suction head plate; 871. withdrawing the suction head hole; 88. a second vertical guide assembly; 89. a third vertical guide assembly; 810. a buffer block;

9. a liquid pump set; 10. an injection pump;

20. a displacement detection assembly; 201. a photoelectric switch; 202. a photoelectric sensing sheet;

30. a liquid level sensing assembly; 40. a reagent bottle; 50. a consumable panel; 501. a reagent plate opening; 60. a display screen; 70. a tubing assembly; 701. blowing and sucking the pipe; 702. a liquid inlet pipe; 703. a main liquid outlet pipe; 704. a liquid separating pipe; 705. feeding the separated waste liquid into a pipe; 706. a main waste liquid inlet pipe; 707. a waste liquid outlet pipe; 80. waste liquid bottle.

Detailed Description

The present invention will be described in further detail with reference to the accompanying drawings and examples. It is to be understood that the specific embodiments described herein are merely illustrative of the invention and are not limiting of the invention. It should be further noted that, for the convenience of description, only some of the structures related to the present invention are shown in the drawings, not all of the structures.

In the description of the present invention, unless expressly stated or limited otherwise, the terms "connected," "connected," and "fixed" are to be construed broadly, e.g., as meaning permanently connected, removably connected, or integral to one another; can be mechanically or electrically connected; either directly or indirectly through intervening media, either internally or in any other relationship. The specific meanings of the above terms in the present invention can be understood in specific cases to those skilled in the art.

In the present invention, unless otherwise expressly stated or limited, "above" or "below" a first feature means that the first and second features are in direct contact, or that the first and second features are not in direct contact but are in contact with each other via another feature therebetween. Also, the first feature being "on," "above" and "over" the second feature includes the first feature being directly on and obliquely above the second feature, or merely indicating that the first feature is at a higher level than the second feature. A first feature being "under," "below," and "beneath" a second feature includes the first feature being directly under and obliquely below the second feature, or simply meaning that the first feature is at a lesser elevation than the second feature.

In the description of the present embodiment, the terms "upper", "lower", "right", etc. are used in an orientation or positional relationship based on that shown in the drawings only for convenience of description and simplicity of operation, and do not indicate or imply that the device or element referred to must have a particular orientation, be constructed and operated in a particular orientation, and thus, should not be construed as limiting the present invention. Furthermore, the terms "first" and "second" are used only for descriptive purposes and are not intended to have a special meaning.

Example one

Fig. 1 is a schematic structural diagram of a nucleic acid detecting apparatus according to an embodiment of the present invention, fig. 2 is a schematic structural diagram of an internal structure of the nucleic acid detecting apparatus according to the embodiment of the present invention, and fig. 3 is a schematic structural diagram of a nucleic acid detecting apparatus according to an embodiment of the present invention, and as shown in fig. 1 to 3, the present embodiment provides a nucleic acid detecting apparatus which can be applied to molecular diagnosis of biological samples such as genotyping, gene mutation detection, pathogen detection, and the like, and can realize integrated and automated operations of processes such as sample pretreatment, nucleic acid extraction and purification, amplification, hybridization detection, and the like.

Specifically, the present embodiment provides a nucleic acid detecting instrument including a housing 1 and a detecting body disposed in the housing 1. The shell 1 is provided with a relatively closed accommodating space, the detection main body is arranged in the accommodating space, and the shell 1 is used for closing the detection main body, so that the nucleic acid detection work is carried out in a relatively closed and clean environment, and the pollution of the external environment to the reagent is reduced. The detection main body comprises a reagent plate 4, an installation frame 2, an oscillation heating component 3 arranged on the installation frame 2, a magnetic attraction component 6, a cover plate component 5 and a liquid transfer device, wherein the reagent plate 4 is arranged on the oscillation heating component 3 and is fixed relative to the oscillation heating component 3. Wherein, the reagent plate 4 is a carrier for carrying out all reactions such as sample pretreatment, sample nucleic acid extraction and purification, sample nucleic acid amplification, molecular hybridization and the like; the mounting frame 2 is used for fixing and supporting a structure in the detection body; the cover plate component 5 is used for automatically closing and opening the nucleic acid amplification tube arranged on the reagent plate 4; the magnetic attraction component 6 is used for magnetic attraction and magnetic release in the nucleic acid extraction process; the oscillation heating component 3 is used for heating and cooling the liquid on the reagent plate 4 in the nucleic acid detection process and realizing the liquid oscillation operation in the nucleic acid hybridization process; the pipetting device is used for realizing liquid transfer, cleaning and waste operations on the reagent plate 4.

For convenience of description, an XYZ coordinate system is established with the directions shown in FIG. 2, wherein the X-direction is the arrangement direction of the reagent plate 4, the Z-direction is the height direction of the nucleic acid detecting apparatus, and the Y-direction is horizontally arranged and determined according to the right-hand rule.

Fig. 4 is a schematic view of a disassembled structure of the housing 1 according to an embodiment of the present invention, as shown in fig. 1 and 4, the housing 1 is a hexahedron structure as a whole, and includes a main housing 11, an opening is disposed on the main housing 11, and the housing 1 further includes a door body disposed at the opening and capable of opening and closing relative to the main housing 11. In order to conveniently place samples, reagents and the like into the accommodating space, the door body comprises a first front door 12 and a second front door 13 which are arranged on the front side of the shell 1, and the first front door 12 and the second front door 13 are arranged side by side along the Y direction and can be opened and closed independently. The first front door 12 is arranged corresponding to the position of the reagent plate 4 so as to facilitate taking and placing of the reagent plate 4 in the accommodating space, and the second front door 13 is arranged corresponding to the reagent bottle storage area in the nucleic acid detecting instrument so as to facilitate placing and replacing of bottled liquid such as pure water, hybridization reagents and the like in the accommodating space.

In the present embodiment, the upper end of the first front door 12 is pivotally connected to the main housing 11, so that the first front door 12 can be opened and closed by rotating relative to the main housing 11, and the second front door 13 adopts a press-and-pop-open door structure. However, it is understood that the first front door 12 may be connected to the main housing 11 at other sides, and the second front door 13 may also be connected to the main housing 11 in a manner of being opened and closed by rotation, and the present embodiment is not limited to the opening forms of the first front door 12 and the second front door 13 and the connection structure with the main housing 11.

For the convenience of detecting the assembly, the disassembly and the maintenance of the main body in the accommodating space, the main body shell 11 and the rear side of the front door pair are also provided with a disassembly and assembly opening for the detection of the main body to pass through, and the door body further comprises a rear door 14 which is detachably arranged at the disassembly and assembly opening. In this embodiment, back door 14 includes two door bodies that set up side by side along the Y direction, and every door body can be dismantled alone to improve dismouting convenience, the maintenance and the change that conveniently carry out local structure to the detection main part simultaneously. It is understood that the rear door 14 may comprise only one door or a plurality of doors.

Further, in order to regulate and control the nucleic acid detecting instrument, a display screen 60 for realizing human-computer interaction is arranged on the housing 1, and the display screen 60 is preferably a touch display screen which can be used for displaying an operation interface so as to facilitate an operator to control the operation of the nucleic acid detecting instrument according to the operation interface, and the display screen 60 can also display the operation state of the nucleic acid detecting instrument in the operation process of the nucleic acid detecting instrument. Optionally, a mounting opening 131 is formed through the second front door 13, and the display screen 60 is embedded in the mounting opening 131 and electrically connected to the controller disposed inside the housing 1.

Because there are heating and exothermic process among the nucleic acid testing process, in order to make the heat effluvium among the accommodation space, main casing body 11 has all link up in its relative both sides and the bottom along the Y direction and has seted up the radiating groove, avoids the heat to pile up in accommodation space.

Further, a frame 15 is protruded from the inner bottom surface of the main housing 11, and a supporting surface for supporting the detection main body is formed on the upper surface of the frame 15. A waste liquid collecting tank 16 is arranged on the frame 15 and used for collecting waste liquid generated in the nucleic acid detection process, so that the waste liquid can be conveniently discharged out of the nucleic acid detector. The tank bottom of waste liquid collecting vat 16 is provided with the discharge port, and the sealed grafting of discharge port has the delivery pipe, and the delivery pipe is arranged in discharging the waste liquid in the waste liquid collecting vat 16 to outside waste liquid bottle to conveniently carry out the emission to the external environment after the centralized processing to the waste liquid.

As shown in fig. 2 and 3, the mounting frame 2 includes a bottom plate 21 parallel to the XY plane and a support frame 22 disposed above the bottom plate 21, and the support frame 22 is a U-shaped structure opened toward the bottom plate 21 and includes a cross beam 221 disposed along the Y direction and vertical beams 222 disposed at both ends of the cross beam 221 and connected between the cross beam 221 and the bottom plate 21 along the Z direction. The cover plate assembly 5, the oscillation heating assembly 3 and the magnetic suction assembly 6 are all arranged on the bottom plate 21, the liquid transfer device is arranged on the support frame 22, and the U-shaped structure of the support frame 22 is arranged, so that the liquid transfer device can conveniently move along the Y direction.

For making things convenient for getting of mounting bracket 2 in accommodation space to put, bottom plate 21 lower surface downward projection is equipped with stabilizer blade 23, and stabilizer blade 23 is provided with two at least side by side along X direction and/or Y direction, has seted up the mounting groove on the frame 15 of shell 1, and during stabilizer blade 23 stretched into the mounting groove, and the lower extreme of stabilizer blade 23 and the tank bottom butt of mounting groove. With this arrangement, while the support stability of the mounting bracket 2 is ensured, the contact area between the bottom plate 21 and the frame 15 can be reduced.

FIG. 5 is a schematic structural diagram of a reagent plate 4 according to an embodiment of the present invention, as shown in FIG. 5, the reagent plate 4 includes a main bearing plate 41 extending along the X direction, the main bearing plate 41 is provided with an amplification hole 411 for placing a nucleic acid amplification tube, a hybridization groove 412 for placing a hybridization solid phase material, a tip cavity 414 for placing a tip, a reagent tube 42 for placing an extraction reagent, and a reaction tube 43 for performing an extraction reaction, and the upper ends of the hybridization groove 412, the reagent tube 42, and the reaction tube 43 are open.

Preferably, the amplification hole 411 is disposed at one end of the reagent plate 4, so that the cover plate assembly 5 can seal and open the opening of the nucleic acid amplification tube, thereby reducing the structural interference. In order to facilitate the arrangement of the nucleic acid amplification tube in the amplification hole site 411, the bearing main board 41 is further provided with a bayonet 413 for clamping a tube cover of the nucleic acid amplification tube, an upper end opening of the bayonet 413 is communicated with an upper end opening of the amplification hole site 411, and the tube cover is opened relative to the tube body of the nucleic acid amplification tube and then is clamped in the bayonet 413, so that the tube cover is prevented from being turned over.

Optionally, the hybridization slot 412, the tip cavity 414, the reagent tube 42 and the reaction tube 43 are sequentially arranged along the direction away from the amplification hole 411 in the X direction, but it is understood that the arrangement shown in fig. 5 is an exemplary structure, and the arrangement positions of the holes, the chambers and the tubes on the reagent plate 4 can be changed, which is not limited in this embodiment.

Furthermore, a plurality of pipette tip tubes 45 are arranged at the bottom of the pipette tip cavity 414 along the X direction for storing a plurality of pipette tips, so as to ensure that the number of replaceable pipette tips in the nucleic acid detection process meets the use requirement and reduce the pollution among detection reagents. In this embodiment, the number of tips that can be placed in the tip cavity 414 is three, but the present invention is not limited thereto. Further, the number of the reagent tubes 42 may be specifically set according to the kind of extraction reagent required for the item of nucleic acid detection to be performed, and the number of the reagent tubes 42 may be, but is not limited to, four.

Preferably, the main bearing board 41 is provided with the sample tube 44, the sample tube 44 is used for storing samples, and the sample tube 44 is used for storing samples alone, so that the method can be applied to a nucleic acid detection project in which an extraction reagent is added first and then the samples are added, and the applicability of the nucleic acid detector is improved. In other embodiments, the sample may be placed directly in the reaction tube 43.

Further, the waste liquid tank 415 is arranged on the bearing main board 41, and the waste liquid tank 415 is used for receiving waste liquid, so that the moving distance of the liquid transfer device in the waste liquid removing process is reduced, and the waste liquid removing operation is convenient. In other embodiments, the waste liquid can be directly sucked into a waste liquid bottle or a waste liquid storage tank outside the reagent plate 4.

In order to seal and protect the reagent in the reagent plate 4 during transportation, a sealing film is also plastically packaged on the upper end face of the reagent plate 4, and the sealing film can be a plastic film, an aluminum film, a paper film or the like. And the plastic film can be torn away from the main bearing plate 41, so that the reagent plate 4 can be normally operated for nucleic acid detection after being placed in the shell 1.

Fig. 6 is a schematic structural diagram of an oscillating heating assembly 3 and a reagent plate 4 according to an embodiment of the present invention, fig. 7 is a schematic structural diagram of the oscillating heating assembly 3 according to an embodiment of the present invention at one viewing angle, fig. 8 is a partial enlarged view of a position I in fig. 7, and fig. 9 is a schematic structural diagram of a split structure according to an embodiment of the present invention, as shown in fig. 6 to 9, the oscillating heating assembly 3 is disposed on a bottom plate 21 and located below a cross beam 221, a plurality of reagent plates 4 are disposed above the oscillating heating assembly 3 side by side along a Y direction, and the oscillating heating assembly 3 is configured to heat a liquid in the reagent plate 4 or drive the reagent plate 4 to reciprocate along the X direction. It is to be understood that only one reagent plate 4 may be provided.

Specifically, the oscillating heating assembly 3 includes a heat treatment unit 31, a heat insulation unit 33 and an oscillating unit 32 which are sequentially arranged from top to bottom, and the reagent plate 4 is fixedly arranged above the heat treatment unit 31. By isolating the heat treatment unit 31 and the oscillation unit 32 by the heat insulation unit 33, the treatment efficiency of the heat treatment unit 31 can be improved, and at the same time, the heat is prevented from being transferred downward into the oscillation unit 32, and the reliability of the use of the oscillation unit 32 is ensured.

Specifically, the heat treatment unit 31 includes a plurality of heating units arranged side by side and at intervals in the X direction, each of which extends in the Y direction. In this embodiment, the plurality of heating units include a nucleic acid amplification tube heating block 311 for heating a nucleic acid amplification tube, a hybridization tank heating plate 314 for heating a hybridization tank 412, a reaction tube heating block 312 for heating a reaction tube 43, and an extraction reagent heating block 313 for heating an extraction reagent, and the arrangement positions of the nucleic acid amplification tube heating block 311, the hybridization tank heating plate 314, the reaction tube heating block 312, and the extraction reagent heating block 313 in the X direction correspond to the positions of the amplification hole sites 411, the hybridization tank 412, the reaction tubes 43, and the reagent tubes 42 on the reagent plate 4 one by one.

In the present embodiment, a plurality of reagent tubes 42 are provided, and the extraction reagent heating block 313 is provided corresponding to one reagent tube 42 located in the middle so that heat can be diffused into the remaining reagent tubes 42 around. In other embodiments, the number of the extraction reagent heating blocks 313 may correspond to the number of the reagent tubes 42.

In order to fix the tubes or grooves on the reagent plate 4 relatively, the upper end surface of each heating block is provided with a tube insertion hole 319 for inserting the corresponding tube structure, when the reagent plate 4 is fixed relative to the oscillation heating unit 3, the nucleic acid amplification tube, the reagent tube 42 and the reaction tube 43 are inserted into the tube insertion hole 319 of the corresponding heating block, and the bottom of the hybridization groove 412 abuts against the hybridization groove heating plate 314. This kind of mode of setting up can improve each heating unit to the heating efficiency who corresponds pipe or groove structure, reduces the heat and runs off, and further guarantees the position relative stability between reagent board 4 and the oscillation heating subassembly 3.

Further, each heating block all is provided with heating film 315 along one side of length direction, and heating film 315 is used for connecting the power, for corresponding heating block provides the heat source, promptly, heats the heating block. The heating block and the heating film 315 are separated, so that the structural arrangement of the heating block can be simplified, and the problems that the heating block is complex in structure, difficult to process and the like and the heating block is caused by direct energization heating of the heating block are avoided. Optionally, the heating film 315 is arranged on the side of the heating block parallel to the YZ, avoiding direct contact of the heating film 315 with the underlying insulating unit 33. The structure of the heating film 315 and the heating plate capable of performing electric heating is a conventional structure in the art and will not be described herein.

Because oscillation heating assembly 3 top is provided with a plurality of reagent boards 4 side by side along the Y direction, all be provided with a plurality of pipe jacks 319 along the Y direction on every heating block, and the number of pipe jack 319 on every heating block and the number and the position one-to-one of reagent board 4 to the realization goes on in step of many times nucleic acid testing experiment. Optionally, the tube insertion holes 319 on the nucleic acid amplification tube heating block 311 and the extraction reagent heating block 313 are cylindrical through holes or blind holes, and the upper end opening end may be provided with a chamfer facilitating insertion of the tube.

The cross-sectional area of the tube insertion hole 319 on the reaction tube heating block 312 is the arc-shaped structure with the opening deviating from the nucleic acid amplification tube heating block 311, and the tube insertion hole 319 penetrates through the upper end, the lower end and one side wall of the reaction tube heating block 312, so as to facilitate heat dissipation, and facilitate the reduction of the weight of the reaction tube heating block 312, meanwhile, the structure of the tube insertion hole 319 on the reaction tube heating block 312 is arranged, which is also beneficial for the magnetic attraction component 6 to carry out magnetic attraction and magnetic release reaction on the reaction liquid in the reaction tube 43, and the structural obstacle between the magnetic attraction component 6 and the reaction tube 43 is reduced.

Further, in order to reduce the overall weight of the oscillating heating module 3, a weight-reducing groove 3110 is provided between adjacent two tube insertion holes 319 to reduce the overall weight of the heating block, thereby reducing the overall weight of the oscillating heating module 3. Preferably, the lightening groove 3110 penetrates the heating block in the Z direction.

Further, in order to meet the refrigeration requirement in the nucleic acid amplification reaction process, a refrigeration unit 317 is arranged at one side of the nucleic acid amplification tube heating block 311 along the length direction, and the refrigeration unit 317 is used for refrigerating the nucleic acid amplification tube heating block 311 so as to refrigerate the reagents in the nucleic acid amplification tube. In the present embodiment, the cooling unit 317 includes a cooling sheet disposed opposite the heating film 315. The structure and the refrigeration principle of refrigeration piece are the conventional setting in this field, and this embodiment need not be repeated. Furthermore, a plurality of cooling fins are arranged side by side along the length direction of the heating block 311 of the nucleic acid amplification tube, so as to satisfy the cooling effect on the whole heating block 311 of the nucleic acid amplification tube.

Since the reaction for amplifying nucleic acid has an exothermic process, a heat dissipation unit 316 is further disposed at one side of the heating block 311 for amplifying nucleic acid in order to dissipate heat as quickly as possible. In this embodiment, to improve the heat dissipation effect, the heat dissipation unit 316 includes a heat sink 3161 and a heat dissipation fan 3162 stacked up and down, and the heat dissipation fan 3162 is connected to the lower side of the heat sink 3161.

The heat sink 3161 includes vertical plates 31611 parallel to the YZ plane, a horizontal plate 31612 horizontally disposed and connected to the vertical plates 31611, and fin portions 31613 parallel to the vertical plates 31611 and connected to the horizontal plate 31612. The vertical plate part 31611 is detachably connected with the nucleic acid amplification tube heating block 311 and is positioned at one side opposite to the heating film 315, and the refrigerating sheet is clamped between the vertical plate part 31611 and the nucleic acid amplification tube heating block 311; both sides of the vertical plate portion 31611 in the vertical direction are provided with a horizontal plate portion 31612, the horizontal plate portion 3162 extends in the direction away from the nucleic acid amplification tube heating block 311, and the horizontal plate portion 31612 positioned below is detachably connected with a cooling fan 3162; the fin 31613 is connected between the two transverse plates 31612 and arranged in parallel and at intervals along the X direction to enhance the heat dissipation effect.

More preferably, a plurality of the transverse plates 31612 are arranged at intervals along the length direction of the nucleic acid amplification tube heating block 311 to increase the heat dissipation effect, and one heat dissipation fan 3162 is detachably connected to each of the transverse plates 31612 located therebelow. This kind of setting more is favorable to improving the radiating effect. In other embodiments, the transverse plate portion 31612 may be provided along the longitudinal direction of the nucleic acid amplification tube heating block 311.

The heat insulation unit 33 comprises a plurality of heat insulation subunits which are respectively arranged below the heating units, the heat insulation subunits are detachably connected with the corresponding heating units, heat insulation treatment is performed on each heating unit, heat insulation effect is improved, heat loss of each heating block can be avoided, and heating effect and heating efficiency of each heating unit during heating are improved.

In the present embodiment, the adiabatic sub-unit located below the nucleic acid amplification tube heating block 311 and the extraction reagent heating block 313 is an adiabatic block 331, and located below the reaction tube heating block 312 is an adiabatic plate 335, the adiabatic plate 335 and the adiabatic block 331 are made of an adiabatic material, and each of the adiabatic sub-units extends in the Y direction to cover a length range of the corresponding heating block. And in order to improve the connection and positioning of the heat insulation block 331 or the heat insulation plate to the corresponding heating block, a positioning groove for positioning can be arranged on the heat insulation block 331 or the heat insulation plate.

The thermal-insulated subunit below hybridization groove hot plate 314 includes a plurality of thermal-insulated posts 332, and thermal-insulated post 332 is vertical to be set up, and is provided with the multiunit along the Y direction interval, and every group includes two thermal-insulated posts 332 that set up the interval along the X direction at least. The insulating column 332 is preferably made of an insulating material.

The insulating unit 33 further comprises an insulating support plate 333 positioned below all insulating subunits, each insulating subunit being arranged on the insulating support plate 333 and being detachably connected to the insulating support plate 333. To further prevent heat from being transferred to the oscillating unit 32, the heat insulation unit 33 further includes heat insulation pillars 334 located below the heat insulation carrier plate 333, the heat insulation pillars 334 are arranged in multiple groups at intervals along the Y direction, and each group at least includes multiple heat insulation pillars 334 arranged at intervals along the X direction. The provision of the heat insulating support 334 can increase the gap between the heat treatment unit 31 and the oscillating unit 32, and promote the flow of air between the heat insulating support plate 333 and the oscillating unit 32, thereby facilitating the diffusion of heat. The insulating support column 334 and the insulating support plate 333 are preferably made of insulating material, but may be made of material having low thermal conductivity.

The oscillating unit 32 includes a support plate 321 parallel to the XY plane, an X-direction guide member 322 located below the support plate 321, and an oscillation driving unit (not shown) for driving the support plate 321 to reciprocate in the X direction. The lower ends of the insulating columns 334 are detachably connected to the support plate 321. In order to reduce the overall weight of the oscillating heating assembly 3, a plurality of lightening holes are provided on the support plate 321.

An X-direction guide assembly 322 is disposed between the support plate 321 and the base plate 21 for guiding the support plate 321 in the X-direction relative to the base plate 21. In this embodiment, the X-direction guiding assembly 322 includes an X-direction guiding track 3221 disposed on the bottom plate 21 along the X-direction and an X-direction slider 3222 disposed on the lower surface of the supporting plate 321 and slidably engaged with the X-direction guiding track 3221, and the structures of the X-direction guiding track 3221 and the X-direction slider 3222 may refer to the structures of the existing linear guiding tracks, and are not described herein again. And in order to improve the motion stability of the supporting plate 321, at least two groups of the X-direction guiding assemblies 322 are arranged at intervals along the Y-direction.

In order to prevent the support plate 321 from separating from the X-direction guide rail 322 when reciprocating in the X direction, two ends of the X-direction guide rail 322 are provided with a stopper 323, and the X-direction slider 3222 abuts against the stopper 323 to realize the limiting when sliding to the end of the X-direction guide rail 322. Preferably, the limiting block 323 is made of elastic material such as rubber, so that the limiting is realized, and meanwhile, the problems of vibration, deformation or loud noise caused by hard collision between the sliding block and the limiting block 323 are avoided.

The oscillation driving unit includes an X-direction lead screw motor (not shown), a fixed end of the X-direction lead screw motor is fixedly connected with the base plate 21, and a driving end of the X-direction lead screw motor is connected with the supporting plate 321. Because the size of backup pad 321 along the Y direction is longer, for improving drive stability and reliability, one side of backup pad 321 is provided with fixed bolster 324, and fixed bolster 324 is provided with two at least along the Y direction interval, and two fixed bolsters 324 connect in the adaptor that same edge Y direction set up, and the adaptor is connected with X to the lead screw motor. The setting of adaptor and fixed bolster 324 can be raised and be used for with X to the hookup location of lead screw motor, when improving the drive reliability, makes things convenient for X to the setting of lead screw motor.

Optionally, the stroke of the support plate 321 reciprocating along the X direction is 10-20 mm. In order to monitor the oscillating stroke of the oscillating heating assembly 3, the oscillating heating assembly 3 further includes a displacement detecting assembly 20 for detecting the movement displacement of the oscillating heating assembly 3 in the X direction. In the present embodiment, the displacement detecting assembly 20 includes a photoelectric switch 201 disposed on one side of the supporting plate 321 and a photoelectric sensing piece 202 disposed on the bottom plate 21. The structure and principle of detecting displacement by the photoelectric switch 201 are conventional in the art and will not be described in detail herein. In other embodiments, other detection devices capable of detecting the oscillation displacement, such as a grating scale, a distance sensor, and the like, may also be provided.

Because the oscillating heating component 3 generates heat with the bottom plate 21 during the rapid oscillation process, in order to avoid the accumulation of heat, a fan is disposed at the position of the support plate 321 and/or the bottom plate 21 corresponding to the X-direction guide component 322 for dissipating heat.

FIG. 10 is a schematic structural view of a cover plate assembly 5 according to an embodiment of the present invention at one viewing angle, FIG. 11 is a schematic structural view of the cover plate assembly 5 according to an embodiment of the present invention at another viewing angle, and FIG. 12 is a schematic structural view of the cover plate assembly 5 according to an embodiment of the present invention at a disassembled state, as shown in FIGS. 10-12, the cover plate assembly 5 is disposed on one side of the oscillating heating assembly 3 and outside an end of the reagent plate 4 where the amplification well site 411 is disposed, for closing and opening an opening of a nucleic acid amplification tube disposed in the amplification well site 411. Specifically, the cover member 5 includes a cover sealing member 51 for closing the opening of the nucleic acid amplification tube and a cover driving member 52 for driving the cover sealing member 51 to move toward or away from the amplification hole site 411. In the present embodiment, the cover plate driving assembly 52 drives the cover plate assembly 5 to move in the vertical direction to improve the convenience of closing or opening the opening of the nucleic acid amplification tube. In other embodiments, the cover driving assembly 52 can also drive the cover sealing assembly 51 to rotate or tilt relative to the horizontal direction, so as to switch the cover sealing assembly 52 between a first position for sealing the nucleic acid amplification tube orifice and a second position for opening the nucleic acid amplification tube orifice.

The cover sealing component 51 comprises a cover plate support and a cover sealing piece 514, the cover plate support comprises a top cover plate 511 and a vertical connecting plate 512 which are vertically connected, the top cover plate 511 is horizontally arranged and is positioned right above the amplification hole site 411, the upper side of the vertical connecting plate 512 is connected with the top cover plate 511, the lower side of the vertical connecting plate 512 is connected with the cover plate driving component 52, and the vertical connecting plate 512 is positioned at the outer side of one end of the reagent plate 4.

The cover 514 is disposed on the inner surface of the top cover plate 511 and away from the vertical connection plate 512, and the cover 514 is disposed opposite to the amplification hole site 411, so that the cover 514 moves downward to close the opening of the nucleic acid amplification tube located at the amplification hole site 411 and moves upward to open the opening of the nucleic acid amplification tube. Optionally, the cap seal 514 is made of a material that cannot adsorb nucleic acid and has a certain elasticity, such as silica gel, PE material, PP material, etc., to achieve tight sealing of the opening.

Preferably, the cover seal 514 is in a sheet-like configuration, which allows the size of the cover seal 514 to be reduced. Further, the lid seal 514 extends in the Y direction and may cover the amplification well sites 411 of the plurality of reagent plates 4 to facilitate the arrangement of the lid seal 514. The number of the amplification hole sites 411 that can be covered by a single cap 514 can be determined according to the number of nucleic acid detection tests that can be simultaneously performed by the nucleic acid detector at one time, so as to facilitate the disassembly, assembly and replacement of the cap 514.

To facilitate the connection between the cover plate driving assembly 52 and the cover sealing assembly 51, the cover sealing assembly 51 further comprises a horizontally disposed transverse connecting plate 513, one side of the transverse connecting plate 513 is connected with the lower side of the vertical connecting plate 512, and the other side of the transverse connecting plate 513 extends in a direction away from the reagent plate 4. In this embodiment, the cover driving assembly 52 includes a cover motor 321, a cover screw 522 connected to an output end of the cover motor 521 and vertically disposed, and a cover nut seat 523 sleeved on the cover screw 522, wherein a fixing portion of the cover motor 521 is connected to the mounting frame 2, and the cover nut seat 523 is connected to the cross connecting plate 513.

In order to facilitate the connection of the cover plate motor 521 and the mounting frame 2, the cover plate assembly 5 further comprises a cover plate motor base 53. The cover plate motor base 53 comprises a mounting plate 531 parallel to the YZ plane, two mounting bases 532 are arranged on one side of the mounting plate 531 away from the top cover plate 511 along the Y direction at intervals, and each mounting base 532 is detachably connected with the bottom plate 21 so as to improve the connection stability with the bottom plate 21. The mounting plate 531 is connected with a motor support plate 533 which is horizontally arranged, and the motor support plate 533 is perpendicular to the mounting plate 531 and is detachably connected with the fixed cover plate motor 521. The mounting plate 531 is further provided with a avoiding hole for the cover plate screw rod 522 to pass through.

Further, in order to further improve the structural stability of the cover plate assembly 5, the mounting plate 531 is provided with a plate penetrating opening 5311 therethrough. The transverse connecting plate 513 includes a first transverse plate portion 5131 and a second transverse plate portion 5132 connected along the X direction, one side of the first transverse plate portion 5131 is connected to the vertical connecting plate 512, the other side of the first transverse plate portion 5131 is connected to the second transverse plate portion 5132, the length of the second transverse plate portion 5132 along the Y direction is greater than the length of the first transverse plate portion 5131 along the Y direction, and the first transverse plate portion 5131 penetrates through the plate penetrating opening 5311 and can vertically lift in the plate penetrating opening 5311.

To improve the smoothness of the Z-direction of the cover sealing assembly 51, the cover sealing assembly 51 includes a cover guiding assembly 54 for guiding the Z-direction movement of the cover sealing assembly 51. The cover plate guiding assembly 54 includes two optical axis bases 541 vertically disposed on the mounting plate 531 at intervals, and an optical axis 542 vertically disposed, and two ends of the optical axis 542 are respectively inserted into the two optical axis bases 541. The second horizontal plate portion 5132 is provided with an optical axis hole 5133, and the optical axis 542 penetrates through the optical axis hole 5133, so that the horizontal connecting plate 513 can vertically lift along the optical axis 542. Further, a linear bearing 543 is connected to the position of the lateral connection plate 513 corresponding to the optical axis hole 5133, and the optical axis 542 is inserted into the linear bearing 543, so that friction during guidance is reduced, and guidance reliability is improved. To further improve the stability and reliability of the guiding, two cover guiding assemblies 54 are disposed at intervals along the Y direction, and the two cover guiding assemblies 54 are disposed on two sides of the cover driving assembly 52 respectively.

To detect and control the stroke of the cover seal assembly 51, the cover assembly 5 further includes a displacement detection assembly 20. In the present embodiment, the cover displacement detecting assembly 20 includes the photoelectric sensing piece 202 disposed on the cross-connecting plate 513 and the photoelectric switch 201 disposed on the mounting plate 531, and the photoelectric switch 201 and the photoelectric sensing piece 202 are disposed opposite to each other. In other embodiments, other detection devices may be used to detect the operation stroke of the capping assembly 51, and the description thereof is omitted.

In order to reduce the weight of the cover plate assembly, lightening holes are formed in the top cover plate 511, the vertical connecting plate 512, the transverse connecting plate 513 and the mounting plate 531.

Fig. 13 is a schematic structural view of a magnetic attraction assembly according to an embodiment of the present invention at one viewing angle, fig. 14 is a schematic structural view of a magnetic attraction assembly according to an embodiment of the present invention at another viewing angle, fig. 15 is a schematic structural view of a magnetic attraction assembly according to an embodiment of the present invention at a disassembled state, and fig. 16 is a partial enlarged view of J in fig. 15, where, as shown in fig. 13 to 16, the magnetic attraction assembly 6 includes a magnetic rod assembly 61 and a magnetic rod driving assembly 62 for driving the magnetic rod assembly 61 to move toward or away from the reagent plate 4. In the present embodiment, the magnetic rod assembly 61 is located below the reagent plate 4, and the magnetic rod driving assembly 62 is used for driving the magnetic rod assembly 61 to vertically lift. This kind of setting can improve compact structure nature, and makes things convenient for magnetism to inhale subassembly 6 and inhale magnetism and release magnetism reaction to the magnetic bead in the mixed liquid in reaction tube 43. In other embodiments, the magnetic rod assembly 61 can move toward or away from the reaction tube 43 with other moving directions, such as horizontal movement or tilting movement.

Specifically, the magnetic rod assembly 61 includes a magnetic rod holder and a magnetic rod 611, and the magnetic rod 611 is vertically and detachably disposed on the magnetic rod holder. By providing the magnetic rod 611, the magnetic rod 611 can be inserted between the reaction tube 43 and the adjacent tube structure on the reagent plate 4, thereby reducing the interference between the magnetic attraction member 6 and the oscillation heating member 3 and the reagent plate 4. Further, a plurality of magnetic rods 611 are arranged side by side along the Y direction, the number and the position of the magnetic rods 611 correspond to the number of the reagent plates 4 and the arrangement position of the reaction tubes 43 one by one, and when the magnetic rods 611 are located at the position where the magnetic attraction reaction is performed, the magnetic rods 611 face the opening position of the tube insertion holes 319 on the reaction tube heating block 312.

The bar magnet support includes the installation strip 612, the horizontal setting that set up along the Y direction and with installation strip 612 detachable connection's installation diaphragm 613, installation diaphragm 613 is connected with bar magnet drive assembly 62. Furthermore, the mounting bar 612 is provided with a positioning portion 6123 protruding downward, the upper surface of the mounting transverse plate 613 is correspondingly provided with a positioning groove 6131, and the positioning portion 6123 is inserted into the positioning groove 6131, so that the mounting transverse plate 613 and the mounting bar 612 are mounted and positioned. The mounting bar 612 and the mounting cross plate 613 are detachably connected by screws penetrating through the groove bottom of the positioning groove 6131 and the mounting portion.

In order to facilitate the arrangement of the magnetic rod 611 on the mounting bar 612, a mounting hole 6121 penetrates through the mounting bar 612 in the vertical direction, and the magnetic rod 611 is inserted into the mounting hole 6121 and is in interference fit with the mounting hole 6121. In order to facilitate taking and placing of the magnetic rod 611, a through opening 6122 is formed in the magnetic rod 611 in a penetrating mode along the Z direction, the through opening 6122 is of a long strip structure, one end of the through opening 6122 penetrates through the side wall of the mounting bar 612, the other end of the through opening 6122 is communicated with the mounting hole 6121, and the opening width of the through opening 6122 is smaller than the diameter of the mounting hole 6121. The through opening 6122 is arranged, so that an installation arm structure with a free end is formed on the installation bar 612, the through opening 6122 is opened under the action of external force through elastic deformation of the installation arm, and the through opening 6122 is closed after the external force is removed, so that the magnetic rod 611 can enter the installation hole 6121 through the through opening 6122. More preferably, the mounting strip 612 is made of an elastic material such as rubber, plastic, or the like.

In this embodiment, the magnetic rod driving assembly 62 adopts a driving mode of a motor matching with a screw rod. Specifically, the magnetic rod driving assembly 62 includes a magnetic attraction driving motor, a magnetic attraction screw rod disposed along the Z direction and having a lower end connected to an output shaft of the magnetic attraction driving motor, and a magnetic attraction nut seat sleeved on the magnetic attraction screw rod and connected to the mounting cross plate 613. In other embodiments, other structures of the magnetic attraction driving assembly capable of achieving vertical lifting of the magnetic rod assembly 61 can be adopted, for example, a linear motor and a hydraulic cylinder are adopted for driving, and the description is omitted here.

To guide the vertical movement of the magnetic bar assembly 61, the magnetic attraction assembly 6 further comprises a magnetic attraction guide assembly 63 for guiding in the vertical direction. In order to facilitate the installation of the magnetic attraction guide component 63 and the magnetic attraction driving motor, the magnetic attraction component 6 further comprises a magnetic attraction motor base 64, and the fixed ends of the magnetic attraction guide component 63 and the magnetic attraction driving motor are both arranged on the magnetic attraction motor base 64. The magnetic motor base 64 can be set with reference to the above-mentioned cover plate motor base 53, and the magnetic guiding component 63 can be set with reference to the structure of the cover plate guiding component 54, which is not described herein again. And for improving the direction stability, the magnetic attraction guide component 63 is provided with two groups at intervals along the Y direction, and the magnetic attraction drive component is positioned between the two groups of magnetic attraction guide components 63.

Further, in order to detect the operation displacement of the magnetic rod assembly 61, the magnetic attraction assembly 6 is provided with a displacement detection assembly 20. In this embodiment, the displacement detecting assembly 20 includes a photoelectric sensing sheet 202 disposed on the mounting horizontal plate 613 and a photoelectric switch 201 disposed on the magnetic motor base 64, and the photoelectric switch 201 and the photoelectric sensing sheet 202 are disposed opposite to each other.

As shown in FIG. 2, the first pipetting mechanism 7 is provided at one end of the mounting frame 2 in the longitudinal direction thereof, and a reagent bottle storage area is provided on one side of the reagent plate 4 in the longitudinal direction thereof on the bottom plate 21, and a plurality of reagent bottles 40 for carrying liquids necessary for nucleic acid detection and washing such as a hybridization solution and pure water are provided on the reagent bottle storage area. The pipetting device comprises a first pipetting mechanism 7 and a second pipetting mechanism 8, wherein the first pipetting mechanism 7 is used for sucking the liquid in the reagent bottle 40, and the second pipetting mechanism 8 is used for taking and placing the reagent on the reagent plate 4. The first pipetting mechanism 7 is arranged above the reagent storage area and is used for pumping the liquid in the reagent bottle 40; the second pipetting means 8 are used for aspirating and transferring liquid on the reagent plate 4.

As shown in fig. 2, in the present embodiment, two rows of reagent bottles 40 are arranged in the reagent bottle storage area side by side along the Y direction, each row of reagent bottles 40 includes five reagent bottles 40 arranged in the X direction side by side, and each reagent bottle 40 can be used for storing different types of liquid. In other embodiments, the number of rows of reagent bottles 40 in the reagent bottle storage area and the number of reagent bottles 40 in each row may be specifically determined according to the type of item for nucleic acid detection.

Fig. 17 is a schematic structural view of the first pipetting mechanism 7 provided in the embodiment of the present invention at one viewing angle, fig. 18 is a schematic structural view of the first pipetting mechanism 7 provided in the embodiment of the present invention at another viewing angle, and fig. 19 is a schematic structural view of the first pipetting mechanism 7 provided in the embodiment of the present invention at a disassembled state, as shown in fig. 17 to 19, the first pipetting mechanism 7 includes a first reagent needle unit 71, a first vertical displacement unit 73 connected to the first reagent needle unit 71 and configured to drive the first reagent needle unit 71 to vertically move up and down, and a first horizontal displacement unit 72 connected to the first vertical displacement unit 73 and configured to drive the first reagent needle unit 71 to horizontally move.

The first horizontal displacement unit 72 includes a connecting member 722 and a first horizontal driving assembly 721, the connecting member 722 is connected to the cross beam 221 of the mounting frame 2, a fixed end of the first horizontal driving assembly 721 is disposed on the connecting member 722, and a driving end of the first horizontal driving assembly 721 is connected to the first vertical displacement unit 73. Further, the first horizontal driving assembly 721 adopts a driving mode of a motor matching with a lead screw, and includes a horizontal driving motor, a horizontal lead screw arranged along the horizontal direction and having one end connected with an output shaft of the horizontal driving motor, and a horizontal nut seat sleeved on the horizontal lead screw, and the horizontal nut seat is connected with the vertical driving assembly. The horizontal driving motor is fixed to a plate-shaped connector 722 through a motor fixing plate 723. In the present embodiment, the horizontal screw is provided in the Y direction to drive the first reagent needle unit 71 to move in the Y direction, and in other embodiments, the horizontal screw may also be provided in the X direction to drive the first reagent needle unit 71 to move in the X direction.

The first vertical displacement unit 73 includes an adapter plate 731 horizontally disposed along the X direction and a first vertical driving assembly 732 disposed on the adapter plate 731, the first vertical driving assembly 732 includes a driving motor fixed on the adapter plate 731, a lead screw vertically disposed and having one end connected to the driving motor, and a nut seat sleeved on the lead screw, and the nut seat is connected to the first reagent needle unit 71.

To guide the first horizontal displacement unit 72 and the first vertical displacement unit 73, the first pipetting mechanism 7 further comprises a first horizontal guide assembly 74 and a first vertical guide assembly 75, the first horizontal guide assembly 74 is arranged on the connecting piece 722, and the first vertical guide assembly 75 is arranged on a guide rail plate 77 which is connected with the adapter plate 731 and is vertically arranged. The first horizontal guiding assembly 74 and the first vertical guiding assembly 75 both adopt a structural form of a rail slider, and the arrangement of linear guiding is realized by adopting a structure of a rail slider, which is a conventional arrangement in the field and is not described herein again. And buffer blocks 76 are connected to both ends of each guide rail in order to limit and buffer the movement of the first horizontal driving assembly 721 and the first vertical driving assembly 732.

The first reagent needle unit 71 includes a horizontally disposed first reagent needle rack 712 and a first reagent needle 711 disposed on the first reagent needle rack 712. In this embodiment, the first reagent needle holder 712 is disposed along the X direction and has one end connected to the slider of the first vertical guide assembly 75. The first reagent needle 711 is vertically disposed, and the first reagent needle 711 is provided in plurality at intervals in the X direction. The number and positions of the first reagent needles 711 correspond one-to-one to the number and positions of the reagent bottles 40 in each row of the reagent bottles in the reagent bottle storage area.

In this embodiment, the first reagent needle 711 is connected to the first reagent needle holder 712 in a plugging manner, which can refer to the installation manner of the magnetic rod 611 and the installation bar 612, and is not described herein again.

Further, for detecting the displacement of the first horizontal displacement unit 72 and the first vertical displacement unit 73, the first pipetting mechanism 7 further includes a first horizontal displacement detection assembly and a first displacement detection assembly, and the first horizontal displacement detection assembly and the first vertical displacement detection assembly all adopt the detection form that the photoelectric switch 201 cooperates with the photoelectric sensing piece 202, which is not repeated herein.

Fig. 20 is a schematic structural view of a second pipetting mechanism provided in an embodiment of the present invention at one viewing angle, fig. 21 is a schematic structural view of the second pipetting mechanism provided in the present invention at another viewing angle, and fig. 22 is a schematic structural view of a second pipetting mechanism provided in an embodiment of the present invention in a disassembled state, and as shown in fig. 20 to 22, the second pipetting mechanism 8 includes a second reagent needle unit 81 for pipetting, a second vertical displacement unit 82 for driving the second reagent needle unit 81 to vertically ascend and descend, a tip picking and placing unit 83 for replacing and inserting a tip, a third vertical displacement unit 84 for driving the tip picking and placing unit 83 to vertically ascend and descend, and a second horizontal displacement unit for driving the second vertical displacement unit 82 and the third vertical displacement unit 84 to move in the Y direction. With this arrangement, the second pipetting mechanism 8 can be made more compact.

The second horizontal moving unit comprises a fixed vertical plate 85 parallel to the XZ plane and a second horizontal driving unit (not shown), wherein the fixed end of the second horizontal driving unit is connected with the cross beam 221, and the driving end of the second horizontal driving unit is connected with the fixed vertical plate 85 and used for driving the connected vertical plate to reciprocate along the Y direction. The second horizontal driving unit may adopt a structural form that a motor is matched with a screw nut, a structural form that a motor is matched with a chain wheel and a chain, or other structural forms that can realize the horizontal movement of the fixed vertical plate 85, and the description is omitted here.

The second vertical displacement unit 82 and the third vertical displacement unit 84 are both provided on one surface of the fixed riser 85. Further, a fixing transverse plate 86 horizontally arranged is vertically connected to the fixing vertical plate 85, fixing ends of the second vertical displacement unit 82 and the third vertical displacement unit 84 are connected to the fixing transverse plate 86, and the second vertical displacement unit 82 and the third vertical displacement unit 84 are arranged side by side along the X direction. In the embodiment, the second vertical displacement unit 82 and the third vertical displacement unit 84 both adopt a driving form that a motor is matched with a screw nut, and the structure is simple and the connection is convenient. In other embodiments, the second vertical displacement unit 82 and the third vertical displacement unit 84 may also be driven by a motor, a rack and pinion, or a linear motor, a hydraulic cylinder, or the like. And the structural form capable of realizing linear driving in the vertical direction is conventional in the field, and is not described herein again.

The suction head taking and placing unit 83 includes a suction head base 831, a suction head sleeve 832 vertically arranged on the suction head base 831, a suction head needle 833 penetrating inside the suction head sleeve 832 and a suction head mouth 834 connected to the lower end of the suction head sleeve 832, wherein the lower end of the suction head needle 833 is hermetically inserted in the suction head mouth 834. The suction head base 831 is detachably connected to a corresponding nut base. In this embodiment, the tip sleeve 832 is a hollow rod-like structure made of stainless steel, and the upper end of the tip 834 is inserted into the lower end of the tip sleeve 832 with interference. The upper end of the suction head needle 833 extends out of the suction head loop bar 832 to be conveniently connected with the liquid inlet pipe 702.

In this embodiment, the installation manner of the nozzle holder 831 and the nozzle sleeve 832 can refer to the installation manner of the magnetic bar 611 and the installation bar 612, which is not described herein again. In this embodiment, the tip loop bar 832 is spaced along the Y-direction to allow for the aspiration and replacement of multiple tips. The number of tip loop bars 832 is the same as the number of nucleic acid detections that can be simultaneously performed by a nucleic acid detector at a single time, and is not limited to 4.

The tip nozzle 834 is for inserting a tip located in the tip cavity 414 on the reagent plate 4, and the second pipetting mechanism 8 further comprises a tip plate 87 for removing a tip in order to facilitate removal of a used tip. The head withdrawing plate 87 is detachably connected with the fixed vertical plate 85, and a head withdrawing hole 871 is formed in the head withdrawing plate 87. The lower end of tip sleeve 832 is inserted into tip retraction aperture 871, and the inner diameter of tip retraction aperture 871 is larger than the maximum outer diameter of tip nozzle 834 and smaller than the maximum outer diameter of the tip. In this arrangement, when the third vertical displacement unit 84 drives the nozzle sleeve 832 with the inserted nozzle to move upwards, the nozzle is separated from the nozzle 834 by the obstruction of the nozzle plate 87, so as to realize the nozzle removing operation.

The second reagent needle unit 81 includes a needle frame 811, a waste liquid needle 812, and a reagent needle bundle 813, the needle frame 811 is detachably connected to a corresponding nut holder, and both the waste liquid needle 812 and the reagent needle bundle 813 are detachably provided on the needle frame 811. In this embodiment, the waste liquid needles 812 and the reagent needle bundles 813 are arranged side by side and at intervals in the X direction, and the dedicated waste liquid needles 812 are designed to discharge waste liquid, whereby contamination between reagents can be reduced. In this embodiment, a plurality of waste liquid needles 812 and reagent needle bundles 813 are arranged in parallel in the Y direction at intervals, and the number of the waste liquid needles 812 and the number of the reagent needle bundles 813 are the same as the number of nucleic acid detections that can be performed by the nucleic acid detector at the same time.

In this embodiment, the needle frame 811 includes a needle holder 8111, a support rod 8112 and a needle mount 8113, the needle holder 8111 is connected to a corresponding nut seat, the upper end of the support rod 8112 is detachably connected to the needle holder 8111, and the lower end of the support rod 8112 is detachably connected to the needle mount 8113. This arrangement can ensure the stability of the needle rack 811 while reducing the overall weight of the needle rack 811, and shorten the required stroke of the reagent needle bundle 813 and the waste needle 812, which require vertical elevation.

Further, the reagent needle bundle 813 includes a needle bundle sleeve 8132 and a plurality of second reagent needles 8131 penetrating through the needle bundle sleeve 8132, and the connection manner of the needle bundle sleeve 8132 and the waste liquid needles 812 and the needle mount 8113 can refer to the installation manner of the magnetic rod 611 and the mounting bar 612, which is not described herein again. In the present embodiment, there are five second reagent needles 8131 in the bundle sleeve 8132, and the number of the second reagent needles 8131 in each bundle sleeve 8132 is the same as that of the first reagent needles 711 in the first pipetting mechanism 7.

In order to prevent the solution from splashing due to too high flow rate of the liquid flowing out through the lower end of the second reagent needle 8131, the second reagent needle 8131 includes a main body 81311 vertically disposed and a guide portion 81312 obliquely connected to the main body 81311, the main body 81311 is integrally formed with the guide portion 81312, the guide portion 81312 is inclined outward with respect to the central axis of the main body 81311, and preferably, the included angle between the guide portion 81312 and the main body 81311 is 5 ° to 10 °. Further, the tip of the second reagent needle 8131 in the same reagent needle bundle 813 is inclined in a different direction.

In order to realize the movement guidance of the second vertical displacement unit 82 and the third vertical displacement unit 84, the second pipetting mechanism 8 further includes a second vertical guiding assembly 88 and a third vertical guiding assembly 89, the second vertical guiding assembly 88 and the third vertical guiding assembly 89 are arranged side by side along the Y direction, the second vertical guiding assembly 88 and the third vertical guiding assembly 89 both adopt the structural form of a guide rail sliding block, and the pipette tip holder 831 and the needle holder 8111 are respectively connected with the sliding blocks of the corresponding vertical guiding assemblies.

In this embodiment, in order to conveniently detect the displacement of the tip taking and placing assembly and the second reagent needle unit 81, the second pipetting mechanism 8 further includes a displacement detecting assembly 20 for detecting the vertical lifting and lowering displacement of the second reagent needle unit 81 and the vertical lifting and lowering displacement of the tip taking and placing assembly, respectively. In this embodiment, the displacement detecting assembly 20 adopts a structural form that the photoelectric switch 201 is matched with the photoelectric sensing piece 202, and in other embodiments, other detecting devices capable of realizing displacement detection can be adopted.

For convenient equipment and dismantlement, fixed riser 85 includes detachable door frame portion 851 and riser portion 852, and door frame portion 851 is lower extreme open-ended U type structure, and riser portion 852 is vertical to be set up and can be dismantled with the both sides of door frame portion 851 and be connected, and fixed diaphragm 86 sets up on door frame portion 851, and two vertical direction subassemblies all set up on riser portion 852.

In order to make the reagent suck the liquid, the pipetting mechanism further comprises a pipeline assembly 70 and a pump unit, wherein the pipeline assembly 70 is used for forming a pipeline required for pipetting, and the pump unit is used for providing power for taking and placing the liquid. In this embodiment, the pipeline assembly 70 includes a suction head pipeline assembly and a reagent needle pipeline assembly, the pump unit includes a syringe pump 10 and a liquid pump set 9, the syringe pump 10 is connected to the suction head taking and placing unit 83 through the suction head pipeline assembly, and the liquid pump set 9 is connected to the first reagent needle unit 71 and the second reagent needle unit 81 through the reagent needle pipeline assembly.

Specifically, fig. 23 is a schematic diagram illustrating the pipeline connection among the suction head pipeline assembly, the syringe pump 10 and the suction head picking and placing unit 83 according to the embodiment of the present invention, as shown in fig. 23, the suction head pipeline assembly includes a plurality of blowing and sucking pipes 701, the number of the blowing and sucking pipes 701 is the same as the number of the suction head needles 833, one end of each blowing and sucking pipe 701 is in sealed communication with the upper end of each suction head needle 833, and the other end of each blowing and sucking pipe 701 is connected to the syringe pump 10. The arrangement of the suction head pipeline component and the injection pump 10 can carry out liquid transfer and blowing and uniformly mixing on the reaction liquid in the nucleic acid extraction process.

Fig. 24 is a schematic diagram illustrating a connection relationship between a liquid pump and a reagent needle pipeline assembly 70 according to an embodiment of the present invention, as shown in fig. 24, a liquid pump set 9 has a plurality of pairs of reagent liquid inlets and reagent liquid outlets, a reagent needle pipeline includes a liquid inlet pipe 702 connected between the liquid pump set 9 and a first reagent needle 711, one end of the liquid inlet pipe 702 is in sealed communication with an upper end of the first reagent needle 711, and the other end of the liquid inlet pipe 702 is in communication with a reagent liquid inlet of the liquid pump set 9. The number of the liquid inlet pipes 702 is the same as that of the first reagent needles 711, and each liquid inlet pipe 702 is communicated with different reagent liquid inlets. The reagent needle pipeline assembly further comprises a main liquid outlet pipe 703, one end of the main liquid outlet pipe 703 is connected to a reagent liquid outlet corresponding to the liquid inlet pipe 702, the other end of each main liquid outlet pipe 703 is communicated with one end of each of the plurality of branch liquid outlet pipes 704, and the other end of each of the plurality of branch liquid outlet pipes 704 is respectively communicated with one second reagent needle 8131 in the plurality of reagent needle bundles 813. As in the present embodiment, there are four reagent needle bundles 813, and each main liquid outlet pipe 703 is connected to four branch liquid outlet pipes 704.

The reagent needle pipeline assembly further comprises a main waste liquid inlet pipe 706 and a plurality of branch waste liquid inlet pipes 707, the number of the branch waste liquid inlet pipes 707 is the same as that of the waste liquid needles 812, one end of each branch waste liquid inlet pipe 707 is communicated with the upper end of one waste liquid needle 812, the other end of each branch waste liquid inlet pipe 707 is communicated with one end of the main waste liquid inlet pipe 706, the other end of the main waste liquid inlet pipe 706 is communicated with a waste liquid inlet in the liquid pump set 9, a waste liquid outlet corresponding to the waste liquid inlet is communicated with one end of a waste liquid outlet pipe 707, and the other end of the waste liquid outlet pipe 707 is communicated with the waste liquid bottle 80. In this embodiment, the waste liquid bottle 80 is made of plastic material, and may contain a disinfectant such as sodium chlorate for waste liquid discharge and nucleic acid product digestion.

In this embodiment, since the first reagent needle 711 extracts the liquid in the reagent bottle 40 located in the reagent bottle storage area, in order to detect whether the liquid level in the reagent bottle 40 meets the use requirement, the reagent bottle storage area is further provided with a liquid level sensing assembly 30 for detecting the liquid level in each reagent bottle 40. The level sensing assembly 30 may be a conventional mature product and will not be described in detail herein. Further, the reagent bottles 40 are arranged on the liquid level sensing assembly 30, and the liquid level sensing assembly 30 is provided with a heating block and a heat sink corresponding to each reagent bottle 40, so as to heat or dissipate heat of the reagent in the reagent bottles 40.

In this embodiment, in order to guarantee inside heat dissipation and the ventilation of nucleic acid detecting instrument, shell 1 is inside to be provided with convulsions filtration system, and convulsions filtration system can promote the air flow among the accommodation space, drives the heat and in time effectively effluvium, and can filter the air, reduces the pollution of the reagent on the reagent board 4 and sample, also can prevent the cross contamination between the inside sample of nucleic acid detecting instrument and the reagent simultaneously. And convulsions filtration system possesses nucleic acid filtering capability, prevents to cause the setting that pollutes convulsions filtration system can refer to current convulsions filtration system's setting to external environment, and here is no longer repeated.

Further, the inside disinfection system that disinfects that still is provided with of shell 1 for disinfect and disinfect the inside equipment of shell 1, further reduce nucleic acid pollution, reduce the influence to the staff. In the present embodiment, the sterilization and disinfection system employs ultraviolet sterilization, but it is understood that other methods capable of sterilization and disinfection can be employed.

The nucleic acid detector provided by the invention integrates the extraction and purification of biological sample nucleic acid, nucleic acid amplification and molecular hybridization detection on one instrument, and an operator can complete all detection processes within 3.5-6 h by only carrying out simple preparation actions (placing the disposable reagent plate 4, placing the amplification tube, placing the hybridization reagent, adding the sample and starting the instrument) to obtain a result. The instrument has the advantages of large treatment capacity (24 samples can be treated at one time), high efficiency and convenience in the whole process, and suitability for clinical detection.

Example two

The present embodiment provides a nucleic acid detection method, which is applied to the nucleic acid detection apparatus of the first embodiment, and is used for high-efficiency automated nucleic acid detection.

The nucleic acid detection method comprises five major steps of early preparation, nucleic acid extraction and purification, nucleic acid amplification reaction and nucleic acid hybridization reaction.

Specifically, the early preparation comprises the following steps:

s101, placing purified water and hybridization solution for nucleic acid detection in a reagent bottle storage area through a second front door 13;

step S102, taking out the sealed reagent plate 4, tearing off the plastic packaging film, adding a sample to be detected into the sample tube 44, inserting the nucleic acid amplification tube 42 into the amplification hole site 411, opening the nucleic acid amplification tube cover, and clamping the nucleic acid amplification tube cover into the bayonet 413;

step S103, putting the reagent plate 4 into the consumable panel 50 through the first front door 12, and closing the shell 1;

step S104, selecting and starting a nucleic acid detection item to be performed through the display screen 60;

steps S101 to S104 are manually performed.

Step S105, the cover plate component 5 moves downwards to close the nozzle of the nucleic acid amplification tube 42;

step S106, the liquid pump set 9 draws the hybridization liquid filling pipeline through the first reagent needle 711;

and S107, starting the air draft filtering system.

Step S105 to step S107 are automated operation steps of the nucleic acid detecting instrument, and step S105, step S106 and step S107 may be performed simultaneously without distinction of sequence.

The extraction and purification of nucleic acid are carried out based on a magnetic bead method, and the steps comprise:

step S201, the second pipetting mechanism 8 moves to enable the sucker nozzle 834 to move to the sucker cavity 414 to insert and take the sucker;

step S202, moving the second pipetting mechanism 8, taking the sample liquid from the sample tube 44, and adding the sample liquid into the reagent tube 42 containing the proteinase K and the magnetic beads;

step S203, the injection pump 10 is operated to make the sucker repeatedly suck and release the liquid in the reagent tube 42 to blow the liquid at least once so as to break up the magnetic beads in the reagent tube 42;

step S204, the second liquid transferring mechanism 8 acts, and the suction head extracts the uniformly mixed proteinase K, magnetic beads and sample mixed liquid into the reaction tube 43 containing the magnetic bead binding liquid;

step S204, electrifying the heating film 315 corresponding to the reaction tube heating block 312 to work, heating the reaction tube 43, and repeatedly blowing the liquid in the reaction tube 43 at least once by the action of the injection pump 10;

in the process, impurities such as nucleic acid and protein are released from the sample, and the nucleic acid is adsorbed on the magnetic beads.

Step S205, the magnetic attraction component 6 acts to make the magnetic rod 611 rise and move to the middle of one side of the reaction tube 43 for magnetic attraction;

this step serves to concentrate the nucleic acids in one region.

Step S205, the second pipetting mechanism 8 and the syringe pump 10 are operated to aspirate the liquid in the reaction tube 43 into the waste liquid tank 415;

because the nucleic acid is concentrated in one area, the nucleic acid can be prevented from being removed when the mixed solution is pumped, so that the nucleic acid is stored to the maximum extent, and the accuracy of nucleic acid concentration measurement is improved.

Step S205 is repeatedly performed at least once.

Step S206, the second pipetting mechanism 8 and the injection pump 10 are operated to suck the liquid from the reagent tube 42 containing the washing liquid into the reaction tube 43, and the magnetic attraction component 6 is operated to move the magnetic rod 611 downwards to be far away from the reaction tube 43;

step S207, the injection pump 10 acts, and liquid in the reaction tube 43 is repeatedly sucked and released through the suction head, so that the liquid in the reaction tube 43 is repeatedly blown and beaten;

this step washes the nucleic acids on the magnetic beads, increasing the purity of the nucleic acids.

Step S208, the magnetic attraction component 6 acts to enable the magnetic rod 611 to rise and move to the middle of one side of the reaction tube 43 for magnetic attraction;

step S209, the liquid in the reaction tube 43 is discarded;

step S210, the magnetic attraction assembly 6 acts to move the magnetic rod 611 downward to a position away from the reaction tube 43, and the heating film 315 corresponding to the reaction tube heating block 312 is energized to heat the reaction tube 43, so as to raise the temperature of the reaction tube 43 and evaporate the residual liquid;

step S211, operating the second pipetting mechanism 8 to discard the pipette tip on the pipette tip 834 into the pipette tip cavity 414;

step S212, the second vertical displacement unit 82 moves downwards, and the suction nozzle 834 inserts a new suction head;

step S213, the second pipetting mechanism 8 is operated, the suction head sucks the eluent into the reaction tube 43, and repeatedly blows and blows the liquid in the reaction tube 43 for at least 1 time;

step S214, the heating film 315 corresponding to the reaction tube heating block 312 is energized and heated to heat the reaction tube 43, so as to elute the nucleic acid;

step S215, the magnetic attraction assembly 6 operates to move the magnetic rod 611 to one side of the reaction tube 43 for magnetic attraction, and collect all the magnetic beads on the upper portion of the tube wall of the reaction tube 43 to make the magnetic beads away from the bottom of the tube.

The nucleic acid amplification realizes the replication process of nucleic acid molecules based on PCR technology or isothermal amplification technology and the like, and the reaction comprises the following steps:

step S301, the cover plate assembly 5 is moved upward to open the opening of the nucleic acid amplification tube;

in step S302, the second pipetting mechanism 8 is operated to aspirate a predetermined amount of nucleic acid from the reaction tube 43 into the nucleic acid amplification tube, and the pipetting is repeated. The tip on tip 834 is discarded.

Step S303, the cover plate component 5 moves downwards to seal the pipe orifice of the nucleic acid amplification pipe;

step S304, the system starts a nucleic acid amplification program to perform a nucleic acid amplification reaction, and during the process, the temperature condition required by the nucleic acid amplification reaction is controlled by the heat treatment module.

The hybridization reaction realizes the hybridization recognition of molecules based on the base complementary principle, and comprises the following steps:

step S401, before the nucleic acid amplification procedure is finished, starting to suck the hybridization solution A into a hybridization tank for preheating (temperature: 35 ℃ -95 ℃);

step S402, after the nucleic acid amplification reaction is finished, the cover plate assembly 5 is operated to open the opening of the nucleic acid amplification tube 42;

step S403, operating the second pipetting mechanism 8 to insert a new tip, operating the second pipetting mechanism 8 and the syringe pump 10 to aspirate the amplification solution in the nucleic acid amplification tube into the hybridization chamber 412 containing solution A via the tip, and starting hybridization;

step S404, the second pipetting mechanism 8 operates to discard the pipette tip on the pipette tip 834;

step S405, oscillating the heating component 3 to drive the hybridization tank 412 to oscillate back and forth along the X direction;

step S406, after the hybridization reaction is performed for the first preset time, the second liquid-transferring mechanism 8 and the liquid pump set 9 are operated, and the waste liquid tube sucks the liquid in the hybridization tank 412 to the waste liquid collecting tank 16;

step S407, the first pipetting mechanism 7, the second pipetting mechanism 8, and the liquid pump unit 9 are operated to aspirate the liquid in the reagent bottle 40 containing the B hybridization liquid into the hybridization chamber 412 through the first reagent needle 711 and the second reagent needle 8131;

step S408, repeating steps S405 to S407 until the liquids in the reagent bottles 40 respectively loaded with the hybridization solution C, the hybridization solution D, and the hybridization solution E in the reagent bottle storage area are sequentially extracted into the hybridization tank 412, and in this process, the oscillating heating unit 3 continues to perform the X-direction oscillating operation.

Step S409, the hybridization reaction is completed, and the oscillation heating unit 3 stops operating.

Step S410, the first pipetting mechanism 7 operates to pump the purified water in the reagent bottle 40 filled with the purified water through the first reagent needle 711, and clean the pipes in the reagent pipe 42 pipe assembly with the purified water;

step S411, the display screen 60 is clicked to execute the disinfection operation, and the detection main body is disinfected.

It is to be noted that the foregoing is only illustrative of the preferred embodiments of the present invention and the technical principles employed. It will be understood by those skilled in the art that the present invention is not limited to the particular embodiments described herein, but is capable of various obvious changes, rearrangements and substitutions as will now become apparent to those skilled in the art without departing from the scope of the invention. Therefore, although the present invention has been described in greater detail by the above embodiments, the present invention is not limited to the above embodiments, and may include other equivalent embodiments without departing from the spirit of the present invention, and the scope of the present invention is determined by the scope of the appended claims.

Claims

1. A nucleic acid detecting instrument, comprising:

a mounting frame (2);

a reagent plate (4), wherein the reagent plate (4) is provided with a nucleic acid amplification tube, a hybridization tank (412), a reaction tube (43) and a reagent tube (42) for storing an extraction reagent;

a cover plate assembly (5) disposed on the mounting frame (2) and capable of moving in a direction toward or away from the nucleic acid amplification tube to close or open a nozzle of the nucleic acid amplification tube;

the heat treatment unit (31) is arranged on the mounting rack (2) and is used for heating or cooling the liquid on the reagent plate (4);

the liquid transfer device is arranged on the mounting rack (2) and is used for sucking and transferring liquid on the reagent plate (4);

the oscillating unit (32) is arranged on the mounting frame (2) and is relatively fixed with the reagent plate (4), and the oscillating unit (32) is used for driving the reagent plate (4) to oscillate in a reciprocating manner along the horizontal direction;

magnetism is inhaled subassembly (6), sets up on mounting bracket (2), and can follow the orientation or keep away from the direction motion of reagent board (4), it is right that magnetism is inhaled subassembly (6) and is used for magnetism and magnetism release to inhale the magnetic bead in the reaction liquid on reagent board (4).

2. The nucleic acid detecting instrument according to claim 1, wherein the reagent plate (4) is extended in an X direction, a plurality of reagent plates (4) are arranged side by side in a Y direction, the cover plate assembly (5) is arranged on one side of the plurality of reagent plates (4) in the X direction, and the magnetic attraction assembly (6) is arranged on the other side of the plurality of reagent plates (4) in the X direction.

3. The nucleic acid detecting apparatus according to claim 2, wherein the cover member (5) includes:

a cover sealing component (51), wherein the cover sealing component (51) comprises a cover sealing piece (514) positioned above the nucleic acid amplification tube, the cover sealing piece (514) is made of elastic materials, and the cover sealing piece (514) is used for sealing the nozzle of the nucleic acid amplification tube;

and the cover plate driving assembly (52) is connected with the cover sealing assembly (51) and is used for driving the cover sealing assembly (51) to move in a translation or rotate so as to enable the cover sealing piece (514) to seal or open the nozzle of the nucleic acid amplification tube.

4. The nucleic acid detecting instrument according to claim 2, wherein the nucleic acid detecting instrument includes an oscillation heating unit (3), the oscillation heating unit (3) includes the heat treatment unit (31), the oscillation unit (32), and a heat insulating unit (33) connected between the heat treatment unit (31) and the oscillation unit (32), and the reagent plate (4) is disposed above the heat treatment unit (31) and fixed with respect to the heat treatment unit (31).

5. The nucleic acid detecting instrument according to claim 4, wherein the heat treatment unit (31) includes a plurality of heating units arranged side by side in the X direction at intervals, and the plurality of heating units are provided below the nucleic acid amplification tube, the hybridization chamber (412), the reaction tube (43), and the reagent tube (42) in correspondence with each other, and each of the heating units extends in the Y direction.

6. The nucleic acid detecting instrument according to claim 5, wherein the heating unit includes a nucleic acid amplification tube heating block (311) located below the nucleic acid amplification tube, the heat treatment unit (31) further includes a cooling unit (317) and a heat radiating unit (316), the heat radiating unit (316) is located at one side of the nucleic acid amplification tube heating block (311) and extends in the Y direction, and the cooling unit (317) is located between the heat radiating unit (316) and the nucleic acid amplification tube heating block (311).

7. The nucleic acid detecting instrument according to claim 5, wherein the heat insulating unit (33) includes a plurality of heat insulating subunits arranged at intervals in the X direction, the heat insulating subunits correspond to the heating units one by one, and the heating units are detachably attached above the heat insulating subunits, each of the heat insulating subunits being made of a heat insulating material.

8. The nucleic acid detecting apparatus according to claim 2, wherein the magnetically attracting member (6) includes:

a magnetic bar assembly (61), wherein the magnetic bar assembly (61) comprises a plurality of magnetic bars (611) which are vertically arranged, and the plurality of magnetic bars (611) are arranged side by side along the Y direction;

the magnetic rod driving assembly (62) is connected with the magnetic rod assembly (61) and used for driving the magnetic rod assembly (61) to move in the vertical direction.

9. The nucleic acid detecting instrument according to claim 8, wherein the magnetic rod assembly (61) further comprises a mounting bar (612) arranged along the Y direction, the mounting bar (612) is provided with a mounting hole (6121), and the lower end of the magnetic rod (611) is inserted into the mounting hole (6121) in an interference manner;

the mounting bar (612) is provided with penetrating openings (6122) in a penetrating manner along the vertical direction, one ends of the penetrating openings (6122) penetrate through the side wall of the mounting bar (612), the other ends of the penetrating openings (6122) are communicated with the mounting holes (6121), the width of the penetrating openings (6122) is smaller than the aperture of the mounting holes (6121), and the penetrating openings (6122) and the mounting holes (6121) are arranged in a one-to-one correspondence manner.

10. The nucleic acid detecting apparatus according to claim 2, wherein a reagent bottle storage section is provided in the nucleic acid detecting apparatus, and a reagent bottle (40) carrying a reagent is stored in the reagent bottle storage section, and the pipetting device includes:

a first pipetting mechanism (7) which can horizontally move and vertically lift relative to the mounting rack (2) and is used for pumping the liquid in the reagent bottle (40);

and the second pipetting mechanism (8) can horizontally move and vertically lift relative to the mounting rack (2) and is used for sucking and transferring the liquid on the reagent plate (4).

11. The nucleic acid detecting instrument according to claim 10, wherein the second liquid-moving mechanism (8) includes a tip taking and placing unit (83), the tip taking and placing unit (83) includes a tip seat (831), a tip loop bar (832) connected to the tip seat (831), a tip nozzle (834) inserted into a lower end of the tip loop bar (832), and a tip needle (833) inserted into the tip loop bar (832) and having a lower end hermetically inserted into the tip nozzle (834), and the second liquid-moving mechanism (8) can drive the tip taking and placing unit (83) to move horizontally and vertically;

the liquid transfer device further comprises an injection pump (10), and the upper end of the suction head needle (833) is connected with the injection pump (10) through a blowing suction pipe (701).

12. The nucleic acid detecting apparatus according to claim 11, wherein the first pipetting mechanism (7) includes at least two first reagent needles (711), and the first pipetting mechanism (7) is capable of moving the first reagent needles (711) horizontally and vertically;

the second pipetting mechanism (8) comprises at least two reagent needle bundles (813), each reagent needle bundle (813) comprising at least two second reagent needles (8131);

the liquid transfer device further comprises a liquid pump unit (9), the liquid pump unit (9) comprises a plurality of pairs of reagent liquid inlets and reagent liquid outlets, each first reagent needle (711) is communicated with one reagent liquid inlet through a liquid inlet pipe (702), each reagent liquid outlet is communicated with one end of a main liquid outlet pipe (703), one end of each main liquid outlet pipe (703) is communicated with one end of a plurality of branch liquid outlet pipes (704), the other end of each branch liquid outlet pipe (704) is communicated with one of the second reagent needles (8131) in the at least two reagent needle bundles (813), and the number of the branch liquid outlet pipes (704) communicated with each main liquid outlet pipe (703) is the same as the number of the reagent needle bundles (813).

13. The nucleic acid detecting apparatus according to claim 12, wherein the second reagent needle (8131) includes a main body portion (81311) vertically arranged and a guide portion (81312) connected to a lower end of the main body portion (81311), the main body portion (81311) is integrally formed with the guide portion (81312), an upper end of the guide portion (81312) is connected to the main body portion (81311), a lower end of the guide portion (81312) extends obliquely downward, and directions of extension of the guide portions (81312) of a plurality of second reagent needles (8131) located in the same reagent needle bundle (813) are different.

14. The nucleic acid detecting apparatus according to claim 12, wherein the second pipetting mechanism (8) further includes a waste liquid needle (812), the waste liquid needle (812) is disposed vertically, the second pipetting mechanism (8) is capable of moving the waste liquid needle (812) in horizontal and vertical directions, the liquid pump unit (9) includes a waste liquid inlet and a waste liquid outlet, the waste liquid inlet and the waste liquid needle (812) are communicated through a waste liquid inlet pipe, and the waste liquid outlet is communicated with the waste liquid bottle (80) through a waste liquid outlet pipe (707).

15. The nucleic acid detecting instrument according to any one of claims 1 to 14, further comprising a housing (1), wherein the mounting rack (2), the reagent plate (4), the cover plate assembly (5), the heat treatment unit (31), the liquid-transferring device, the oscillation unit (32) and the magnetic attraction assembly (6) are all disposed inside the housing (1), an opening is disposed on the housing (1), a door body for closing or opening the opening is disposed at the opening, and the reagent plate (4) can enter and exit from the outside through the opening;

an air draft filtering system and/or a sterilization and disinfection system are/is arranged inside the shell (1).

16. The nucleic acid detecting instrument according to any one of claims 2 to 14, wherein the nucleic acid detecting instrument further includes a consumable panel (50), the consumable panel (50) is provided with a plurality of reagent plate openings (501) side by side along a Y direction, the reagent plate openings (501) extend along an X direction, the reagent plate (4) includes a supporting main plate (41), the nucleic acid amplification tubes, the hybridization tank (412), the reaction tubes (43), and the reagent tubes (42) are all disposed on the supporting main plate (41), a lower surface of the supporting main plate (41) is erected on the consumable panel (50), and the nucleic acid amplification tubes, the hybridization tank (412), the reaction tubes (43), and the reagent tubes (42) all extend into the reagent plate openings (501).

17. A method for detecting a nucleic acid, which is applied to the nucleic acid detecting apparatus according to any one of claims 1 to 16, and which comprises:

a pre-detection treatment, comprising the steps of: opening a cap of the nucleic acid amplification tube; the cover plate component (5) closes the nozzle of the nucleic acid amplification tube;

nucleic acid extraction and purification, which is performed based on a magnetic bead method, and which includes: adding a sample into the reagent tube (42) containing the proteinase K and the magnetic beads by the liquid transferring device, and uniformly mixing; the liquid transfer device sucks the mixed liquid of the uniformly mixed protease K, the magnetic beads and the sample liquid into a reaction tube (43) containing a magnetic bead binding solution; the heat treatment unit (31) regulates and controls the temperature condition required by the reaction of the reaction tube (43) so as to crack cells and release nucleic acid; after releasing nucleic acid, the magnetic attraction component (6) moves back and forth along the direction close to or far away from the reagent plate (4) and is matched with liquid extraction and transfer of the liquid transfer device to realize adsorption, washing and elution of nucleic acid on magnetic beads so as to obtain purified nucleic acid;

a nucleic acid amplification reaction comprising: the cover plate component (5) moves to open the nozzle of the nucleic acid amplification tube; pipetting a certain amount of nucleic acid into the nucleic acid amplification tube by using a pipetting device; the cover plate component (5) moves to close the nozzle of the nucleic acid amplification tube; starting a nucleic acid amplification process to perform a nucleic acid amplification reaction, during which temperature conditions required for the nucleic acid amplification reaction are controlled by the heat treatment unit (31);

a hybridization reaction comprising: moving a cover plate component (5) to open the nozzle of the nucleic acid amplification tube; the pipetting device draws the amplification solution in the nucleic acid amplification tube into a hybridization tank (412); the liquid-transfering device can be used for successively pumping different hybridization liquids into the hybridization tank (412), in the meantime, the heat treatment module (31) can be used for regulating and controlling the temperature required by the reaction, and the oscillation unit (32) can be used for driving the reagent plate (4) to horizontally and reciprocally oscillate so as to realize the specific binding, washing and color development of the amplification products and the probes on the hybridization membrane.