CN116694452A - Nucleic acid PCR amplification hybridization reaction instrument and amplification hybridization all-in-one machine - Google Patents
Nucleic acid PCR amplification hybridization reaction instrument and amplification hybridization all-in-one machine Download PDFInfo
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- CN116694452A CN116694452A CN202310915585.9A CN202310915585A CN116694452A CN 116694452 A CN116694452 A CN 116694452A CN 202310915585 A CN202310915585 A CN 202310915585A CN 116694452 A CN116694452 A CN 116694452A
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- 102000039446 nucleic acids Human genes 0.000 title claims abstract description 55
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- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
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- C12Q1/6844—Nucleic acid amplification reactions
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Abstract
The invention provides a nucleic acid PCR amplification hybridization reaction instrument and an amplification hybridization integrated machine, and relates to the technical field of molecular biology and the technical field of nucleic acid amplification hybridization equipment. The nucleic acid PCR amplification hybridization reaction instrument comprises: the device comprises a machine base, a machine shell, a machine cover and a reaction module. The nucleic acid PCR amplification hybridization reaction instrument integrates the reaction chambers of the nucleic acid amplification instrument and the hybridization instrument into a totally-enclosed three-dimensional device, and the PCR amplification hybridization reaction device is provided with a cover, so that the PCR reaction chamber and the hybridization reaction chamber can be enclosed into a sealed space, and aerosol pollution is effectively avoided. The nucleic acid PCR amplification hybridization reaction instrument is provided with a plurality of mounting grooves for placing the PCR amplification hybridization reaction device, and each mounting groove is mutually separated, so that the mutual interference of a plurality of amplification reactions is avoided, the accuracy of the amplification reactions is improved, and in addition, the equipment has high convenience and can meet the requirement of simultaneous analysis of a single or a plurality of samples.
Description
Technical Field
The invention relates to the technical field of molecular biology and the technical field of nucleic acid amplification hybridization equipment, in particular to a nucleic acid PCR amplification hybridization reaction instrument and an amplification hybridization integrated machine.
Background
The basic principle of PCR (polymerase chain reaction) technology is similar to the natural replication process of DNA, and its specificity depends on oligonucleotide primers complementary to both ends of the target sequence. PCR consists of three basic reaction steps of denaturation-annealing-extension: (1) denaturation of template DNA: heating the template DNA to 93 ℃ for a certain time, and then dissociating the double-stranded template DNA or the double-stranded DNA formed by PCR amplification to make the template DNA become single-stranded so that the template DNA is combined with the primer to prepare for the next round of reaction; (2) annealing (renaturation) of template DNA to primer: after the template DNA is denatured into single strands by heating, the temperature is reduced to about 55 ℃, and the primer is combined with the complementary sequence of the single strands of the template DNA in a pairing way; (3) extension of the primer: under the action of Taq DNA polymerase, the DNA template-primer conjugate uses dNTP as reaction raw material and target sequence as template, and synthesizes a new semi-reserved copy chain complementary with template DNA chain according to the base pairing and semi-reserved copy principle. By repeating the three processes of denaturation, annealing and extension, more "semi-reserved replication chains" can be obtained, and the new chains can be used as templates for the next cycle. Every cycle is completed for 2-4 minutes, and the target gene to be amplified can be amplified for millions of times within 2-3 hours.
In molecular laboratories, PCR and hybridization methods, experiments are generally performed using two semi-or fully automated instruments. At present, there are also technical platforms for integrating PCR and hybridization methods by microfluidic technology, but the following drawbacks exist:
(1) The microfluidic chip integrated with amplification and hybridization has poor experimental effect, and because a plurality of reaction chambers, valve structures, microfluidic channels and the like are integrated on a planar glass or other substrate, the technical precision is very high, and poor experimental effect is easy to occur;
(2) The common gene amplification instrument and hybridization instrument are mainly manual or semi-automatic, have complicated process and difficult operation, and the problems of easy corrosion of a reaction chamber, rust of each structural part and the like after long-term use, and possibly cause the problems of unstable actual PCR temperature, incapability of meeting experimental requirements of products and the like;
(3) Whether the traditional amplification hybridization method or the microfluidic hybridization method is easy to generate aerosol pollution, which is also the most critical technical defect.
In view of this, the present invention has been made.
Disclosure of Invention
The invention aims to provide a nucleic acid PCR amplification hybridization reaction instrument and an amplification hybridization integrated machine so as to improve the experimental effect of amplification hybridization integration, simplify the operation flow and avoid aerosol pollution.
The invention is realized in the following way:
in a first aspect, the present invention provides a nucleic acid PCR amplification hybridization reaction apparatus comprising: the reaction device comprises a machine base, a machine shell, a machine cover and a reaction module, wherein the machine shell is arranged above the machine base, the machine cover is movably connected with the machine shell, the machine cover, the machine shell and the machine base form a cavity, and the reaction module is arranged in the cavity;
the shell is provided with a control display module, a waste liquid outlet and a power line port;
the reaction module comprises a mounting seat and a temperature control unit for respectively and independently controlling amplification and hybridization reactions; the top of the mounting seat is provided with a plurality of mounting grooves for placing the PCR amplification hybridization reaction device, the bottom of the mounting groove is provided with a waste liquid hole, the temperature control unit comprises a plurality of temperature control devices, and the periphery of each mounting groove is provided with at least one temperature control device;
the two adjacent temperature control devices are provided with gaps, and the waste liquid holes and the gaps are communicated with a waste liquid outlet arranged on the shell so as to realize the discharge of waste liquid;
a pump and a circuit board are also arranged in the shell, and a liquid inlet of the pump is connected with a gap or a waste liquid hole at the bottom of the mounting groove through a pipeline; the circuit board is electrically connected with the temperature control unit, the control display module and the power line port.
The nucleic acid PCR amplification hybridization reaction instrument can meet the amplification hybridization reaction of various PCR amplification hybridization reaction devices. The control display module can display the running state, the working process and the quality parameters of the equipment. The circuit board can realize the control system for driving the whole device by being electrically connected with the temperature control unit, the control display module and the power line port, can collect system data, control the power supply, and cooperate with each functional module in the control equipment and perform information transmission work, and comprises information transmission without limitation of a wired signal interface, a power interface and a wireless data transmission interface.
The control display module comprises a touch screen, for example, and is used as a control panel and a display panel for displaying the running states of equipment and systems and for manually modifying data parameters and changing the current running state.
The reaction module is used for realizing PCR amplification and hybridization reaction of the PCR amplification hybridization reaction device, realizing accurate temperature control of the PCR amplification and hybridization reaction through the temperature control unit, and discharging reacted waste liquid from a waste liquid hole at the bottom of the mounting groove under the action of the pump. The pump is used for draining and pushing the amplified nucleic acid into the hybridization reaction chamber in a mode of hybridization liquid pressure difference, and the hybridization liquid is pumped out after hybridization is completed, so that hybridization reaction is completed. The liquid flow in the experimental process is jointly formed by a pump liquid and a liquid injection hole injection pressure on the PCR amplification hybridization reaction device.
The nucleic acid PCR amplification hybridization reaction instrument integrates the nucleic acid amplification instrument and the reaction chamber of the hybridization instrument into a totally-enclosed three-dimensional device, and the PCR amplification hybridization reaction device is provided with the cover, so that the PCR reaction chamber and the hybridization reaction chamber can be enclosed into a sealed space, and aerosol pollution is effectively avoided.
The nucleic acid PCR amplification hybridization reaction instrument is provided with a plurality of mounting grooves (namely small reaction chambers) for placing the PCR amplification hybridization reaction device, and each mounting groove is mutually separated, so that the mutual interference of a plurality of amplification reactions is avoided, and the accuracy of the amplification reactions is improved.
The nucleic acid PCR amplification hybridization reaction instrument provided by the invention has high convenience and can meet the requirement of simultaneous analysis of single or multiple samples. The method is favorable for the integrated reaction of nucleic acid amplification and hybridization, improves the automation degree of multi-channel nucleic acid detection, and greatly reduces the occurrence of false positive pollution and other problems.
In order to avoid the problems of corrosion of the reaction chamber, rust of each structural component and the like, most of the nucleic acid PCR amplification hybridization reaction instruments provided by the inventor are made of plastic components, and the temperature control device is made of aluminum metal materials which are not easy to rust.
In an alternative embodiment, the reaction module further comprises a heat dissipation port, a temperature sensor and a first switch, wherein the heat dissipation port is positioned below the temperature control unit, the heat dissipation port is positioned on the side wall of the casing beside the temperature control unit, and the temperature sensor is positioned on the side wall or the bottom of the mounting groove; the first switch is electrically connected with the pump. The temperature sensor can collect the temperature of the mounting groove on the control display module in real time. The heat dissipation of reaction module is accelerated in order to accelerate in the setting of thermovent, realizes faster reaction temperature regulation and control.
In an alternative embodiment, the reaction module further comprises a solenoid valve electrically connected to the first switch. The first switch may be used to control the pump and the solenoid valve.
In an alternative embodiment, the reaction module comprises a mount, an amplification reaction module, and a hybridization reaction module, and the amplification reaction module comprises: the device comprises a first heat radiation port, a first temperature sensor and an amplification temperature control unit; the hybridization reaction module includes: the device comprises a second heat radiation port, a second temperature sensor, a hybridization temperature control unit and a first switch.
The amplification reaction module and the hybridization reaction module which are respectively and independently arranged can respectively and independently realize amplification and hybridization reactions without mutual interference.
In an alternative embodiment, the first heat dissipation port is disposed below the expansion temperature control unit, and the first temperature sensor is located at a side wall or a bottom of the mounting groove. The second heat dissipation port is arranged below the hybridization temperature control unit, and the second temperature sensor is positioned on the side wall or the bottom of the mounting groove.
In an alternative embodiment, the heat sink is a heat sink channel opening in the interior wall of the housing. The heat dissipation device is used for dissipating heat of the temperature control unit and the TEC semiconductor.
In an alternative embodiment, the TEC semiconductor is drive controlled by a temperature control unit, the semiconductor being used to provide both heating and cooling.
In a preferred embodiment of the present invention, 2 temperature control devices are disposed on the periphery of each mounting groove, and a gap is formed between the two temperature control devices, and the waste liquid hole and the gap are communicated with the waste liquid outlet disposed on the casing.
In a preferred embodiment of the present invention, the temperature control device includes, but is not limited to, a heating and cooling plate, a heating and cooling column, a heating and cooling tube, or a heating and cooling table. The temperature control device is selected from TEC semiconductor heating and refrigerating plates, for example.
In a preferred embodiment of the present invention, the mounting groove comprises a PCR amplification groove and a hybridization reaction groove, and the PCR amplification groove and the hybridization reaction groove are communicated through a flow channel. The PCR amplification tank corresponds to a PCR amplification chamber or a PCR reaction chamber of the PCR amplification hybridization reaction apparatus. The hybridization reaction tank corresponds to a hybridization reaction chamber of a PCR amplification hybridization reaction device. The flow channel corresponds to the drainage groove of the PCR amplification hybridization reaction device.
In an alternative embodiment, the flow channel is provided with or without an inclined surface. When the inclined surface is provided, the depth of the end close to the hybridization reaction tank may be set larger than the depth of the end far from the hybridization reaction tank. This facilitates the flow of amplified products from the PCR chamber of the PCR amplification hybridization reaction apparatus into the hybridization reaction chamber. The inclined surface is inclined at an angle of 5-40 degrees compared with the horizontal plane.
The PCR amplification hybridization reaction device comprises an amplification hybridization integrated gene chip disclosed in patent publication No. CN 116004371A.
In a preferred embodiment of the invention, the bottom of the mounting seat is further provided with a baffle and a waste liquid chamber in sequence, the waste liquid chamber and a liquid outlet of the pump extend into the waste liquid chamber through a setting pipeline, and the waste liquid chamber is provided with a waste liquid chamber outlet communicated with a waste liquid outlet on the shell. The baffle is used for separating the mounting seat and the waste liquid chamber, wherein the baffle is provided with an opening so as to extend a pipeline connected with the liquid inlet of the pump to a gap of the mounting groove.
In an alternative embodiment, the pump is a peristaltic pump. In other embodiments, the sample waste after the hybridization reaction is discharged by a peristaltic pump in combination with a hybridization reaction module.
In a preferred embodiment of the present invention, the control display module is located at a front end of the housing, and the waste liquid outlet and the power line port are located at a rear end or a side end of the housing.
In an alternative embodiment, the control display module further comprises a transparent cover, which facilitates monitoring of spotting, sample addition, drainage and readout of chip hybridization results.
In a preferred embodiment of the present invention, a second switch is further disposed on the housing, and the second switch is electrically connected to the circuit board. The second switch is used for controlling the starting and the closing of the whole PCR amplification hybridization instrument.
In a preferred embodiment of the present invention, the cover is hinged to the housing. Including but not limited to dual covers and single covers.
In a preferred embodiment of the present invention, at least 3 foot pads are disposed below the base; such as rubber foot pads, which can resist shock and reduce noise.
Preferably, each foot pad is further provided with a sucking disc, so that the stability of the machine base can be ensured, and the phenomenon that the machine base influences the internal reaction rate of the reaction chamber due to vibration when hybridization reaction occurs is avoided.
In a second aspect, the invention provides a nucleic acid PCR amplification hybridization integrated machine, which comprises a nucleic acid PCR amplification hybridization reaction instrument and a PCR amplification hybridization reaction device.
In a preferred embodiment of the present invention, the PCR amplification hybridization reaction device is a gene chip, and the liquid drain at the bottom of the PCR amplification hybridization reaction device is disposed corresponding to the liquid drain hole at the bottom of the mounting groove.
The PCR amplification hybridization reaction device comprises a cover and a base, wherein a liquid injection hole is opened on the cover, and the base comprises a PCR reaction chamber, a drainage groove, a hybridization reaction chamber and a liquid outlet.
For the PCR reaction chamber, the bottom is an inclined plane, and the depth of one end of the PCR reaction chamber close to the hybridization reaction chamber is larger than the depth of one end of the PCR reaction chamber far away from the hybridization reaction chamber, so that the amplification product in the PCR reaction chamber can flow into the hybridization reaction chamber from the PCR reaction chamber. Wherein the hybridization reaction chamber is provided with a hybridization membrane supporting plate, and the inclined plane is inclined at an angle of 5-40 degrees compared with the horizontal plane. The PCR reagent, hybridization solution, blocking solution and enzyme-labeled solution are injected through the injection hole.
In an alternative embodiment, a drainage hole for facilitating drainage is formed in the middle of the hybridization membrane supporting plate. The drainage holes are arranged to facilitate the hybridization reaction liquid to flow downwards from the hybridization membrane support plate.
The structure includes an amplification hybridization integrated gene chip disclosed in patent publication No. CN 116004371A.
Compared with the prior art, the invention has the beneficial effects that:
the nucleic acid PCR amplification hybridization reaction instrument provided by the invention can meet the amplification hybridization reaction of various PCR amplification hybridization reaction devices. The nucleic acid PCR amplification hybridization reaction instrument integrates the reaction chambers of the nucleic acid amplification instrument and the hybridization instrument into a totally-enclosed three-dimensional device, and the PCR amplification hybridization reaction device is provided with a cover, so that the PCR reaction chamber and the hybridization reaction chamber can be enclosed into a sealed space, and aerosol pollution is effectively avoided.
The nucleic acid PCR amplification hybridization reaction instrument is provided with a plurality of mounting grooves (namely small reaction chambers) for placing the PCR amplification hybridization reaction device, and each mounting groove is mutually separated, so that the mutual interference of a plurality of amplification reactions is avoided, and the accuracy of the amplification reactions is improved.
The nucleic acid PCR amplification hybridization reaction instrument provided by the invention has high convenience and can meet the requirement of simultaneous analysis of single or multiple samples. The method is favorable for the integrated reaction of nucleic acid amplification and hybridization, improves the automation degree of multi-channel nucleic acid detection, and greatly reduces the occurrence of false positive pollution and other problems.
In order to avoid the problems of corrosion of the reaction chamber, rust of each structural component and the like, most of the nucleic acid PCR amplification hybridization reaction instruments provided by the inventor are made of plastic components, and the temperature control device is made of aluminum metal materials which are not easy to rust.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings that are needed in the embodiments will be briefly described below, it being understood that the following drawings only illustrate some embodiments of the present invention and therefore should not be considered as limiting the scope, and other related drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a schematic diagram of a first view angle structure of a nucleic acid PCR amplification hybridization reaction apparatus according to the present invention;
FIG. 2 is a schematic diagram of a second view angle structure of the nucleic acid PCR amplification hybridization reaction apparatus provided by the invention;
FIG. 3 is a plan view of the overall structure of FIG. 2;
FIG. 4 is a schematic diagram of the structure of a PCR amplification hybridization reaction chip.
Icon: 1-a waste liquid outlet; 2-a power line port; 3-foot pads; 4-a housing; 5-a stand; 6-a power switch; 7-the front end of the machine; 8-controlling a display module; 9-mounting seats; 10-mounting grooves; 11-a cover; 12-PCR reaction chamber; 13-drainage grooves; 14-a liquid outlet; 15-a reaction chamber cover; 16-hybridization reaction chamber; 17-a rubber sealing ring; 18-a liquid injection hole; 19-a base; 20-gaps; 21-a baffle; 22-heating a cooling plate; 23-front end cavity; 24-heat dissipation port.
Detailed Description
For the purpose of making the objects, technical solutions and advantages of the embodiments of the present invention more apparent, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention, and it is apparent that the described embodiments are some embodiments of the present invention, but not all embodiments of the present invention. The components of the embodiments of the present invention generally described and illustrated in the figures herein may be arranged and designed in a wide variety of different configurations.
Thus, the following detailed description of the embodiments of the invention, as presented in the figures, is not intended to limit the scope of the invention, as claimed, but is merely representative of selected embodiments of the invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
It should be noted that: like reference numerals and letters denote like items in the following figures, and thus once an item is defined in one figure, no further definition or explanation thereof is necessary in the following figures.
In the description of the present invention, it should be noted that the terms "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", "clockwise", "counterclockwise", and the like indicate an azimuth or a positional relationship based on that shown in the drawings, or an azimuth or a positional relationship in which the inventive product is conventionally put in use, are merely for convenience of describing the present invention and for simplifying the description, and do not indicate or imply that the apparatus or element to be referred to must have a specific azimuth, be constructed and operated in a specific azimuth, and thus should not be construed as limiting the present invention. Furthermore, the terms "first," "second," "third," and the like are used merely to distinguish between descriptions and should not be construed as indicating or implying relative importance.
Furthermore, the terms "horizontal," "vertical," "overhang," and the like do not denote a requirement that the component be absolutely horizontal or overhang, but rather may be slightly inclined. As "horizontal" merely means that its direction is more horizontal than "vertical", and does not mean that the structure must be perfectly horizontal, but may be slightly inclined.
In the description of the present invention, it should also be noted that, unless explicitly specified and limited otherwise, the terms "disposed," "mounted," "connected," and "connected" are to be construed broadly, and may be, for example, fixedly connected, detachably connected, or integrally connected; can be mechanically or electrically connected; can be directly connected or indirectly connected through an intermediate medium, and can be communication between two elements. The specific meaning of the above terms in the present invention will be understood in specific cases by those of ordinary skill in the art.
Example 1
Referring to fig. 1 and 2, the present embodiment provides a nucleic acid PCR amplification hybridization reaction apparatus and a nucleic acid PCR amplification hybridization integrated machine, which includes: the reaction device comprises a machine base 5, a machine shell 4, a machine cover 11 and a reaction module, wherein the machine shell 4 is arranged above the machine base 5, the machine cover 11 is hinged with the machine shell 4, the machine cover 11, the machine shell 4 and the machine base 5 form a cavity, and the reaction module is arranged in the cavity; the chamber includes a front end cavity 23. The reaction module comprises a mounting seat 9 and a temperature control unit for controlling amplification and hybridization reactions; 10 mounting grooves 10 for placing PCR amplification hybridization reaction chips are formed in the top of the mounting seat 9, and the mounting grooves 10 are arranged in two rows, and each row is 5 rows. In order to facilitate the drainage, a waste liquid hole is formed at the bottom of the installation groove 10. The nucleic acid PCR amplification hybridization reaction instrument integrates the reaction chambers of the nucleic acid amplification instrument and the hybridization instrument into a totally-enclosed three-dimensional device, and the PCR amplification hybridization reaction chip is provided with a cover, so that the PCR reaction chamber 12 and the hybridization reaction chamber 16 can be enclosed into a sealed space, and aerosol pollution is effectively avoided. The nucleic acid PCR amplification hybridization reaction instrument is provided with a plurality of mounting grooves 10 (i.e. small reaction chambers) for placing the PCR amplification hybridization reaction device, and each mounting groove 10 is mutually separated, so that the mutual interference of a plurality of amplification reactions is avoided, and the accuracy of the amplification reactions is improved. The nucleic acid PCR amplification hybridization reaction instrument has high convenience and can meet the requirement of simultaneous analysis of single or multiple samples. The method is favorable for the integrated reaction of nucleic acid amplification and hybridization, improves the automation degree of multi-channel nucleic acid detection, and greatly reduces the occurrence of false positive pollution and other problems.
Specifically, the power switch 6, the waste liquid discharge port 1 and the power line port 2 are provided on the casing 4, and as shown in fig. 1, the power switch 6, the waste liquid discharge port 1 and the power line port 2 are provided at the rear of the nucleic acid PCR amplification hybridization reaction apparatus. In other embodiments, the waste liquid outlet 1 and the power line port 2 may be located at the side end of the housing 4, or the waste liquid outlet 1 may be located at the side end of the housing 4, and the power line port 2 may be located at the rear of the housing 4.
The reaction module in the chamber comprises a mounting seat 9, an amplification reaction module and a hybridization reaction module, and the amplification reaction module and the hybridization reaction module comprise a temperature control unit for controlling amplification and hybridization reactions. The reaction module is used for realizing PCR amplification and hybridization reaction of the PCR amplification hybridization reaction device, and the temperature control unit can be used for realizing accurate temperature control of the PCR amplification and hybridization reaction.
The temperature control unit comprises a plurality of temperature control devices, and at least one temperature control device is arranged on the periphery of each mounting groove 10. The mounting groove 10 includes a PCR amplification groove and a hybridization reaction groove, and the PCR amplification groove and the hybridization reaction groove are communicated through a flow channel. The PCR amplification well corresponds to a PCR amplification chamber or a PCR reaction chamber 12 of the PCR amplification hybridization reaction apparatus. The hybridization reaction tank corresponds to the hybridization reaction chamber 16 of the PCR amplification hybridization reaction apparatus. The flow channel corresponds to the drainage groove 13 of the PCR amplification hybridization reaction device.
In an alternative embodiment, the flow channel is provided with or without an inclined surface. When the inclined surface is provided, the depth of the end close to the hybridization reaction tank may be set larger than the depth of the end far from the hybridization reaction tank. This facilitates the flow of amplified products from the PCR chamber 12 of the PCR amplification hybridization reaction apparatus into the hybridization reaction chamber 16. The inclined surface is inclined at an angle of 5-40 degrees compared with the horizontal plane.
The PCR amplification hybridization reaction device comprises an amplification hybridization integrated gene chip disclosed in patent publication No. CN 116004371A.
In this embodiment, the temperature control device is a heating and cooling plate 22, and is specifically selected from TEC semiconductor heating and cooling plates 22. The adjacent two heating and cooling plates 22 are provided with gaps 20, and the waste liquid holes and the gaps 20 are communicated with the waste liquid discharge outlet 1 arranged on the shell 4 so as to realize the discharge of waste liquid. In order to realize the rapid discharge of the waste liquid, a pump is further arranged in the shell 4, and a liquid inlet of the pump is connected with a waste liquid hole at the bottom of the installation groove 10 through a pipeline and a gap 20 in the temperature control device. The reacted waste liquid is discharged from the waste liquid hole at the bottom of the installation groove 10 under the action of the pump. The pump is used for draining and pushing the amplified nucleic acid into the hybridization reaction chamber 16 by means of the difference of hybridization liquid pressure, and the hybridization liquid is pumped out further after hybridization is completed, so that hybridization reaction is completed. The liquid flow during the experiment is formed by the pump liquid and the liquid injection pressure of the liquid injection hole 18 on the PCR amplification hybridization reaction device.
The waste liquid holes include, but are not limited to, round holes, square holes or diamond holes, and can be used as long as the function of liquid discharge can be satisfied. The waste liquid hole is arranged corresponding to the liquid outlet 14 at the bottom of the hybridization reaction chamber 16 of the PCR amplification hybridization reaction chip. In an alternative embodiment, a waste liquid conducting tube is placed in the gap 20, the waste liquid in the tube leading to the waste liquid outlet 1.
The amplification reaction module includes: a first heat sink, a first temperature sensor, and an amplification heating/cooling plate 22; the hybridization reaction module includes: a second heat sink, a second temperature sensor, a hybrid heating and cooling plate 22, and a first switch. The heat dissipation port 24 is positioned below the heating and cooling plate 22, the heat dissipation port 24 is positioned on the side wall of the casing beside the temperature control unit, and the temperature sensor is positioned on the side wall or bottom of the mounting groove 10; the first switch is electrically connected with the pump; the reaction module further comprises an electromagnetic valve, and the electromagnetic valve is electrically connected with the first switch.
In an alternative embodiment, the heat sink 24 is a heat sink channel opening on the interior wall of the housing. The heat dissipation device is used for dissipating heat of the temperature control unit and the TEC semiconductor.
In an alternative embodiment, the TEC semiconductor is drive controlled by a temperature control unit, the semiconductor being used to provide both heating and cooling.
Referring to fig. 4, the bottom of the mounting seat 9 is further provided with a baffle 21 and a waste liquid chamber in sequence, the waste liquid chamber and a liquid outlet of the pump extend into the waste liquid chamber through a setting pipeline, and the waste liquid chamber is provided with a waste liquid chamber outer discharge port communicated with the waste liquid discharge port 1 on the shell 4; the pump is a peristaltic pump.
The baffle 21 is used to separate the mounting seat 9 from the waste liquid chamber. Under the action of the peristaltic pump, the waste liquid flows out from the liquid outlet 14 of the PCR amplification hybridization reaction chip, flows into a pipeline arranged in the gap 20 through a waste liquid hole at the bottom of the mounting groove 10, enters the peristaltic pump, is discharged from the liquid outlet end of the peristaltic pump along the pipeline to be gathered in the waste liquid pool, and is finally discharged from the waste liquid outlet 1 of the waste liquid pool.
The casing 4 (the position of the front end 7) is also provided with a control display module 8. The control display module 8 may present the equipment operating state, the work progress and the quality parameters. The circuit board can realize a control system for driving the whole device by being electrically connected with the temperature control unit, the control display module 8 and the power line port 2, and can collect system data, control the power supply, cooperate with each functional module in the control equipment and perform information transmission work, including information transmission without limitation to a wired signal interface, a power interface and a wireless data transmission interface.
In this embodiment, the control display module 8 includes a single-chip microcomputer main control board module and a touch screen, the single-chip microcomputer main control board module is used for driving a control system of the whole device, collecting system data, controlling a power supply, and controlling each functional module in the equipment to work cooperatively with information transmission, including a wired signal interface, a power interface and a wireless data transmission interface.
The touch screen is used as a control panel and a display panel and is used for displaying the running states of equipment and systems and manually modifying data parameters to change the current running state.
The control display module 8 also comprises a transparent cover which is convenient for monitoring sample application, sample adding, drainage and reading of the chip hybridization result.
A circuit board is also arranged in the casing 4 and is electrically connected with the temperature control unit, the control display module 8 and the power line port 2.
4 rubber foot pads 3 are arranged below the machine base 5, and the rubber foot pads 3 can resist vibration and reduce noise. Each foot pad 3 is also provided with a suction cup. The stability of the stand 5 can be ensured, and the influence of the stand 5 on the internal reaction rate of the reaction chamber due to vibration is avoided when hybridization reaction occurs.
Referring to FIG. 3, the PCR amplification hybridization reaction chip includes a reaction chamber cover 15 and a base 19; the reaction chamber cover 15 is opened with a liquid injection hole 18, and the base 19 includes a PCR reaction chamber 12, a drainage groove 13, a hybridization reaction chamber 16 and a liquid drain port 14.
The reaction chamber cover 15 and the base 19 can be connected in an adsorption sealing way through a rubber sealing ring 17; the PCR reaction chamber 12 is connected with a drainage groove 13, the drainage groove 13 is connected with a hybridization reaction chamber 16, and the hybridization reaction chamber 16 is connected with a liquid outlet 14.
For the PCR reaction chamber, the bottom is an inclined plane, and the depth of one end of the PCR reaction chamber close to the hybridization reaction chamber is larger than the depth of one end of the PCR reaction chamber far away from the hybridization reaction chamber, so that the amplification product in the PCR reaction chamber can flow into the hybridization reaction chamber from the PCR reaction chamber. Wherein the hybridization reaction chamber is provided with a hybridization membrane supporting plate, and the inclined plane is inclined at an angle of 5-40 degrees compared with the horizontal plane. The PCR reagent, hybridization solution, blocking solution and enzyme-labeled solution are injected through the injection hole.
In an alternative embodiment, a drainage hole for facilitating drainage is formed in the middle of the hybridization membrane supporting plate. The drainage holes are arranged to facilitate the hybridization reaction liquid to flow downwards from the hybridization membrane support plate.
The PCR amplification and hybridization method comprises the following steps:
placing the PCR amplification hybridization reaction chip into a hybridization reaction chamber 16, injecting 600 microliters of hybridization solution preheated to 45 DEG from a solution injection hole, starting a peristaltic pump, sucking the hybridization solution into the hybridization reaction chamber, and closing the peristaltic pump; the prepared nucleic acid sample was added to the PCR reagent tube, and 5. Mu.l of paraffin was injected, which served to prevent the reaction solution or hybridization solution from volatilizing.
The power supply is turned on, the power switch is turned on, and the singlechip is used for driving the touch screen to serve as a control panel and a display panel. The temperature sensor is used for detecting the temperature of the current PCR reaction chamber to obtain temperature data, the temperature data are transmitted to the master control board of the singlechip, the singlechip is displayed on the touch screen, the data are transmitted through the touch screen, the touch screen can display the temperature of the current reaction chamber and the current reaction stage, and meanwhile, the touch screen can be used for controlling the reaction of the current reaction chamber.
The temperature of the PCR reaction chamber is controlled by using a TEC semiconductor, wherein the single chip microcomputer controls the PCR reaction program as follows: the PCR reaction chamber was heated to 95 °, maintained for 30 seconds, then cooled to 65 °, and maintained for 30 seconds. Repeating the heating and cooling cycle for more than 35 times;
in the reaction process, the main control board records the reaction data.
The main control board analyzes and uploads the data after the reaction to the management platform, displays the data on the touch screen display module, reminds a user that the detection is completed, and monitors the temperature in the reaction chamber after the start;
the singlechip controls the heating and cooling plate 22 to promote the reaction and record the reaction data; after the reaction is finished, an instruction can be transmitted through the touch screen, so that the control display module controls the peristaltic pump to discharge waste liquid, and a new PCR amplification hybridization reaction chip is used in the next experiment.
The above is only a preferred embodiment of the present invention, and is not intended to limit the present invention, but various modifications and variations can be made to the present invention by those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. A nucleic acid PCR amplification hybridization reaction apparatus, comprising: the reaction device comprises a machine base, a machine shell, a machine cover and a reaction module, wherein the machine shell is arranged above the machine base, the machine cover is movably connected with the machine shell, a cavity is defined by the machine cover, the machine shell and the machine base, and the reaction module is arranged in the cavity;
the shell is provided with a control display module, a waste liquid outlet and a power line port;
the reaction module comprises a mounting seat and a temperature control unit for respectively and independently controlling amplification and hybridization reactions; the top of the mounting seat is provided with a plurality of mounting grooves for placing the PCR amplification hybridization reaction devices, the bottom of the mounting groove is provided with a waste liquid hole, the temperature control unit comprises a plurality of temperature control devices, and at least one temperature control device is arranged on the periphery of each mounting groove;
the two adjacent temperature control devices are provided with gaps, and the waste liquid holes and the gaps are communicated with the waste liquid discharge outlet arranged on the shell so as to realize the discharge of waste liquid;
a pump and a circuit board are also arranged in the shell, and a liquid inlet of the pump is connected with the gap or a waste liquid hole at the bottom of the mounting groove through a pipeline; the circuit board is electrically connected with the temperature control unit, the control display module and the power line port.
2. The nucleic acid PCR amplification hybridization reaction instrument according to claim 1, wherein the reaction module further comprises a heat sink, a temperature sensor and a first switch, wherein the heat sink is positioned below the temperature control unit, the heat sink is positioned on a side wall of the casing beside the temperature control unit, and the temperature sensor is positioned on a side wall or bottom of the mounting groove; the first switch is electrically connected with the pump;
preferably, the reaction module further comprises a solenoid valve electrically connected to the first switch.
3. The nucleic acid PCR amplification hybridization reactor according to claim 2, wherein the reaction module comprises a mount, an amplification reaction module, and a hybridization reaction module, and the amplification reaction module comprises: the device comprises a first heat radiation port, a first temperature sensor and an amplification temperature control unit; the hybridization reaction module includes: the device comprises a second heat radiation port, a second temperature sensor, a hybridization temperature control unit and a first switch.
4. The nucleic acid PCR amplification hybridization reaction apparatus according to claim 3, wherein 2 temperature control devices are provided on the outer periphery of each of the mounting grooves, and a gap is provided between the two temperature control devices, and the waste liquid hole and the gap are communicated with the waste liquid discharge port provided on the housing;
the mounting groove comprises a PCR amplification groove and a hybridization reaction groove, and the PCR amplification groove and the hybridization reaction groove are communicated through a flow channel;
preferably, the temperature control device is a heating and cooling plate, a heating and cooling column, a heating and cooling pipe or a heating and cooling table.
5. The nucleic acid PCR amplification hybridization reaction instrument according to claim 4, wherein a baffle and a waste liquid chamber are further arranged at the bottom of the mounting seat in sequence, the waste liquid chamber and a liquid outlet of the pump extend into the waste liquid chamber through a setting pipeline, and a waste liquid chamber outer discharge port communicated with the waste liquid discharge port on the shell is arranged in the waste liquid chamber;
preferably, the pump is a peristaltic pump.
6. The nucleic acid PCR amplification hybridization reaction apparatus according to claim 1, wherein the control display module is located at a front end of the housing, and the waste liquid discharge port and the power line port are located at a rear end or a side end of the housing.
7. The nucleic acid PCR amplification hybridization reaction apparatus according to claim 6, wherein a second switch is further provided on the housing, and the second switch is electrically connected to the circuit board.
8. The nucleic acid PCR amplification hybridization reaction apparatus as set forth in claim 1, wherein the cover is hinged to the housing;
preferably, at least 3 foot pads are arranged below the stand;
preferably, each of the foot pads is further provided with a suction cup.
9. A nucleic acid PCR amplification hybridization all-in-one machine, characterized in that it comprises the nucleic acid PCR amplification hybridization reaction instrument and the PCR amplification hybridization reaction device according to any one of claims 1 to 8.
10. The nucleic acid PCR amplification hybridization all-in-one machine according to claim 9, wherein the PCR amplification hybridization reaction device is a gene chip, and a liquid drain port at the bottom of the PCR amplification hybridization reaction device is provided corresponding to a liquid waste hole at the bottom of the mounting groove.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310915585.9A CN116694452A (en) | 2023-07-24 | 2023-07-24 | Nucleic acid PCR amplification hybridization reaction instrument and amplification hybridization all-in-one machine |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310915585.9A CN116694452A (en) | 2023-07-24 | 2023-07-24 | Nucleic acid PCR amplification hybridization reaction instrument and amplification hybridization all-in-one machine |
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| CN116694452A true CN116694452A (en) | 2023-09-05 |
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| CN202310915585.9A Pending CN116694452A (en) | 2023-07-24 | 2023-07-24 | Nucleic acid PCR amplification hybridization reaction instrument and amplification hybridization all-in-one machine |
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