CN110724631A - Heating control device of nucleic acid amplification instrument - Google Patents
Heating control device of nucleic acid amplification instrument Download PDFInfo
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- CN110724631A CN110724631A CN201911047219.6A CN201911047219A CN110724631A CN 110724631 A CN110724631 A CN 110724631A CN 201911047219 A CN201911047219 A CN 201911047219A CN 110724631 A CN110724631 A CN 110724631A
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- 238000010438 heat treatment Methods 0.000 title claims abstract description 225
- 230000003321 amplification Effects 0.000 title claims abstract description 30
- 238000003199 nucleic acid amplification method Methods 0.000 title claims abstract description 30
- 108020004707 nucleic acids Proteins 0.000 title claims abstract description 29
- 102000039446 nucleic acids Human genes 0.000 title claims abstract description 29
- 150000007523 nucleic acids Chemical class 0.000 title claims abstract description 29
- 230000017525 heat dissipation Effects 0.000 claims abstract description 40
- 238000006243 chemical reaction Methods 0.000 claims abstract description 27
- 238000007789 sealing Methods 0.000 claims abstract description 5
- 238000006073 displacement reaction Methods 0.000 claims description 23
- 238000000137 annealing Methods 0.000 claims description 10
- 238000005485 electric heating Methods 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 9
- 238000004925 denaturation Methods 0.000 claims description 6
- 230000036425 denaturation Effects 0.000 claims description 6
- 125000006850 spacer group Chemical group 0.000 claims description 4
- 108020004414 DNA Proteins 0.000 description 11
- 238000003752 polymerase chain reaction Methods 0.000 description 10
- 238000002955 isolation Methods 0.000 description 6
- 238000001816 cooling Methods 0.000 description 5
- 239000012634 fragment Substances 0.000 description 5
- 102000053602 DNA Human genes 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 238000010586 diagram Methods 0.000 description 2
- 239000013615 primer Substances 0.000 description 2
- 238000005057 refrigeration Methods 0.000 description 2
- 239000003155 DNA primer Substances 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000012864 cross contamination Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L7/00—Heating or cooling apparatus; Heat insulating devices
- B01L7/52—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
- B01L7/525—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples with physical movement of samples between temperature zones
- B01L7/5255—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples with physical movement of samples between temperature zones by moving sample containers
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
-
- G—PHYSICS
- G05—CONTROLLING; REGULATING
- G05D—SYSTEMS FOR CONTROLLING OR REGULATING NON-ELECTRIC VARIABLES
- G05D23/00—Control of temperature
- G05D23/19—Control of temperature characterised by the use of electric means
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/04—Closures and closing means
- B01L2300/041—Connecting closures to device or container
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/18—Means for temperature control
- B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/18—Means for temperature control
- B01L2300/1894—Cooling means; Cryo cooling
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Clinical Laboratory Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Health & Medical Sciences (AREA)
- Physics & Mathematics (AREA)
- Hematology (AREA)
- Analytical Chemistry (AREA)
- Dispersion Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Engineering & Computer Science (AREA)
- Automation & Control Theory (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
Abstract
The invention relates to a heating control device of a nucleic acid amplification instrument, which comprises a chip mechanism, a heating module, a heat dissipation module, a conveying mechanism, a heating cover plate mechanism and a control unit, wherein the chip mechanism comprises a chip mounting bracket and a chip, the chip is mounted on the chip mounting bracket, the chip comprises a reaction bottom plate and capillary tubes, grooves are formed in the reaction bottom plate, the capillary tubes are arranged in the grooves, and at least two temperature sensors are arranged on the chip; the chip mechanism is also provided with a heating cover plate mechanism for sealing and heating the chip; the heating cover plate mechanism is arranged on the chip mechanism, the conveying mechanism comprises a moving base, and the heating module and the heat dissipation module are arranged on the moving base from top to bottom; the device can quickly and accurately realize temperature rise and fall of the PCR reaction.
Description
Technical Field
The invention belongs to the technical field of nucleic acid amplification, and particularly relates to a heating control device of a nucleic acid amplification instrument.
Background
The nucleic acid amplification technology, especially the digital Polymerase Chain Reaction (PCR) technology, is a molecular biological technology for amplifying specific DNA molecular fragment, which uses DNA molecule as template and uses a pair of artificially synthesized specific oligonucleotide primers to quickly amplify the specific DNA molecular fragment by means of DNA Polymerase enzymatic Reaction, and has extremely important action in biology. The basic process of PCR reaction is divided into three steps. Firstly, DNA denaturation (94 ℃) is carried out, and a double-stranded DNA template is broken by hydrogen bonds under the action of heat to form single-stranded DNA; step two, annealing (55 ℃), reducing the temperature of the system, and combining the primer and the DNA template to form a local double strand; and step three, extending (72 ℃) to synthesize a DNA chain complementary with the template by taking dNTP as a raw material to extend from the 5 end to the 3 end of the primer under the action of Taq enzyme. The PCR instrument is used for performing denaturation, annealing and polymerization treatment on the amplified DNA fragments by controlling samples to reach different temperatures so as to achieve the purpose of amplifying the quantity of the DNA fragments by times. Therefore, the accuracy of temperature control and the speed of temperature rise and fall directly affect the efficiency of DNA fragment amplification.
Patent document CN109929753A discloses a blower module of a digital nucleic acid amplification instrument, which comprises a blower module frame, a heat sink, and a cooling plate, wherein the blower module further comprises a variable speed fan, a temperature sensor, a temperature controller, and a fan speed controller; the variable speed fan, the temperature sensor, the temperature controller and the fan rotating speed controller are electrically connected, the rotating speed of the variable speed fan and the temperature of the chip are in one-to-one correspondence, and the rotating speed of the variable speed fan can be adjusted in real time according to the temperature of the chip, so that heat dissipation is rapidly carried out and the heat dissipation process is controlled;
patent document CN106047688A discloses a polymerase chain reaction apparatus and a temperature control system thereof, wherein the system comprises: the heating module is attached to the porous reaction plate and is used for adjusting the temperature of the porous reaction plate; a temperature sensor for detecting the temperature of the multi-well reaction plate; and the controller is respectively connected with the heating module and the temperature sensor and is used for controlling the heating module to regulate the temperature of the porous reaction plate. The invention can rapidly heat or cool the porous reaction plate of the PCR instrument, thereby realizing rapid adjustment of the temperature of the sample.
Although the above patent documents can achieve temperature control to some extent, the three stages of PCR reaction are all executed on the unified heating and cooling module, which may affect the temperature control effect, and especially cannot raise the temperature quickly.
Disclosure of Invention
In order to solve the technical problems, the invention provides a heating control device and a heating control method for a nucleic acid amplification instrument, which can quickly and accurately realize temperature rise and fall of a PCR reaction.
On one hand, the invention provides a heating control device of a nucleic acid amplification instrument, which is characterized by comprising a chip mechanism, a heating module, a heat dissipation module, a transmission mechanism, a heating cover plate mechanism and a control unit, wherein the chip mechanism comprises a chip mounting bracket and a chip, the chip is mounted on the chip mounting bracket, the chip comprises a reaction bottom plate and capillary tubes, grooves are formed in the reaction bottom plate, the capillary tubes are arranged in the grooves, and at least two temperature sensors are arranged on the chip; the chip mechanism is also provided with a heating cover plate mechanism for sealing and heating the chip; the heating cover plate mechanism is arranged on the chip mechanism, the conveying mechanism comprises a moving base, and the heating module and the heat dissipation module are arranged on the moving base from top to bottom;
the heating module comprises a first heating area, a second heating area and a third heating area; the first heating area, the second heating area and the third heating area respectively comprise a first heat-conducting plate, a second heat-conducting plate, a first-stage refrigerating sheet and a second-stage refrigerating sheet, and the first heat-conducting plate, the first-stage refrigerating sheet, the second heat-conducting plate and the second-stage refrigerating sheet are sequentially arranged from top to bottom;
the heat dissipation module comprises a heat dissipation support and a fan, the first heating area, the second heating area and the third heating area are sequentially arranged on the heat dissipation support from left to right, and the fan is arranged below the heat dissipation support;
the control unit is used for controlling the heating module, the heating cover plate mechanism and the radiating module to work according to the real-time temperature detected by the temperature sensor; the control unit is used for controlling the operation of the conveying mechanism according to the position of the chip.
Preferably, a heat dissipation plate is further arranged between the heat dissipation bracket and the fan, and a plurality of heat dissipation holes are formed in the heat dissipation plate.
Preferably, in the extending stage, the conveying mechanism control chip is located on the first heat-conducting plate of the first heating region, in the denaturing stage, the conveying mechanism control chip is located on the first heat-conducting plate of the second heating region, and in the annealing stage, the conveying mechanism control chip is located on the first heat-conducting plate of the third heating region.
Preferably, a left isolation block is arranged between the first heating area and the second heating area, and a right isolation block is arranged between the second heating area and the third heating area.
Preferably, the chip is further provided with a displacement sensor, the displacement sensor is used for detecting whether the conveying mechanism accurately conveys the chip to the corresponding first heat-conducting plate during the nucleic acid amplification reaction, and the length and the width of the first heat-conducting plate are equal to those of the bottom of the chip mechanism.
Preferably, the conveying structure further comprises two fixed bases, and the moving base is mounted on the two fixed bases.
Preferably, all be provided with the spout on two fixed bases, the both sides of moving the base are located the spout, just it is provided with the motor to move the base below, the control unit control motor drives it is at the spout internal horizontal motion to move the base.
Preferably, the heating cover plate mechanism comprises a heating cover plate and a heating cover plate support, an electric heating sheet is arranged on the bottom surface of the heating cover plate, the control unit controls the electric heating sheet to heat, the heating cover plate support comprises a top cover plate and a side cover plate, and the side cover plate is connected to the edge of the top cover plate.
Preferably, be equipped with two bases on the chip mounting support, be provided with the chip mount table on two bases, the chip both sides are provided with the screens, the screens of chip joint respectively on the chip mount table, the heating cover lid closes in the chip top.
Preferably, an elastic mechanism is arranged between the electric heating piece and the chip, so that the chip is prevented from being damaged and crushed.
In another aspect, the present invention provides a method for controlling heating of a nucleic acid amplification apparatus, comprising the steps of:
s1: the control unit controls the conveying mechanism to convey the chip mechanism to the first heat-conducting plate of the first heating area, the displacement sensor is used for detecting whether the bottom of the chip mechanism corresponds to the first heat-conducting plate of the first heating area, if so, the control unit controls the conveying mechanism to stop, if not, the conveying mechanism continues conveying the chip mechanism until the displacement sensor detects that the bottom of the chip mechanism corresponds to the first heat-conducting plate of the first heating area, and then the control unit controls the first heating area to heat until the temperature T1 set in the first heating area is reached and the expected time T1 is kept;
s2: after the temperature is kept for T1 time at the temperature of T1 in the first heating area, the control unit controls the conveying mechanism to convey the chip mechanism to the first heat-conducting plate of the second heating area, and the displacement sensor is used for detecting whether the bottom of the chip mechanism corresponds to the first heat-conducting plate of the second heating area or not, if so, the control unit controls the conveying mechanism to stop, and if not, the conveying mechanism continues to convey the chip mechanism until the displacement sensor detects that the bottom of the chip mechanism corresponds to the first heat-conducting plate of the second heating area; the control unit controls the heating of the second heating area, and if the temperature T2 set by the second heating area is not reached after the expected time T2, the control unit controls the heating cover plate mechanism to heat until the temperature T2 set by the second heating area is reached and the expected time T3 is kept;
s3: after keeping at the temperature of the second heating zone T2 for T3 time, the control unit turns off the heat source of the heating cover plate mechanism;
s4: the control unit controls the conveying mechanism to convey the chip mechanism to the first heat-conducting plate of the third heating area, the displacement sensor is used for detecting whether the bottom of the chip mechanism corresponds to the first heat-conducting plate of the third heating area, if so, the conveying mechanism is controlled to stop through the control unit, and if not, the conveying mechanism continues to convey the chip mechanism until the displacement sensor detects that the bottom of the chip mechanism corresponds to the first heat-conducting plate of the third heating area; the control unit controls the power of the fan according to the temperature displayed by the temperature sensor on the chip, if the temperature displayed by the temperature sensor is far greater than the temperature T3 set by the third heating area, the power of the fan is increased, and if the temperature displayed by the temperature sensor is lower than the temperature T3 set by the third heating area, the control unit controls the third heating area to heat until the desired time T4 is kept.
Preferably, in the extension reaction stage, that is, when the chip mechanism is in the first heating region, if the temperature of the temperature sensor is far lower than the set temperature T1 within the desired time, the control unit may control the heating lid mechanism to heat until the temperature rises to T1;
preferably, in the annealing reaction stage, that is, when the chip mechanism is in the third heating region, if the temperature of the temperature sensor is far lower than the set temperature T3 within the desired time, the control unit may control the heating lid mechanism to heat until the temperature rises to T3;
compared with the prior art, the invention has the beneficial effects that:
(1) according to the invention, the chip mechanism is respectively conveyed to three different heating areas through the movable bottom plate according to three different stages of nucleic acid amplification reaction, so that the reaction liquid of a capillary in the chip can realize rapid temperature rise and fall, particularly, the upper end of the chip is provided with the electric grade plate, the lower end of the chip is provided with the primary refrigerating plate and the secondary refrigerating plate, namely, the upper end and the lower end of the chip are both provided with heat sources, therefore, the temperature can be rapidly raised in a denaturation area of nucleic acid amplification, and meanwhile, if the temperature of other areas can not be rapidly raised, the heat sources at the upper end and the lower end can also be used for rapid and accurate temperature.
(2) The heating cover plate mechanism provided by the invention not only can play a role in heating, but also can be used for sealing a chip, so that a reaction system in the chip is safer and more reliable, and no cross contamination exists.
(3) The heating control method of the nucleic acid amplification instrument provided by the invention can quickly and accurately realize temperature rise and drop of PCR reaction.
(4) The control device and the control method provided by the invention can quickly realize accurate temperature rise and fall by controlling the heating module and the electric heating sheet of the heating cover plate mechanism through the control unit according to different temperature requirements of three PCR stages.
Drawings
FIG. 1 is a cross-sectional view of a heated cover plate mechanism and a chip mechanism provided by the present invention.
FIG. 2 is a schematic view of a single heating zone of the heating module provided by the present invention;
FIG. 3 is a schematic structural view of a heating module and a heat dissipation module provided in the present invention;
fig. 4 is a schematic structural diagram of a conveying mechanism provided by the present invention.
The reference numerals denote:
1. a chip; 2. heating the cover plate; 3. a voltage level chip; 4. a base; 5. a top cover plate; 6. a side cover plate; 7: a first heat-conducting plate; 8. a first-stage refrigeration sheet; 9: a secondary refrigeration plate; 10: a first heating zone; 11. a second heating zone; 12. a third heating zone; 13. a heat dissipation plate; 14. a heat dissipation bracket; 15. a fan; 16. a left spacer block; 17. a right spacer block; 18. moving the base; 19. a fixed base; 20. a second heat-conducting plate.
Detailed Description
The invention is further illustrated by way of example in the following description with reference to the accompanying drawings:
as shown in fig. 1-4, fig. 1 is a cross-sectional view of a heated cover plate mechanism and a chip mechanism provided by the present invention. FIG. 2 is a schematic view of a single heating zone of the heating module provided by the present invention; FIG. 3 is a schematic structural view of a heating module and a heat dissipation module provided in the present invention; fig. 4 is a schematic structural diagram of a conveying mechanism provided by the present invention.
On one hand, the invention provides a heating control device of a nucleic acid amplification instrument, which comprises a chip mechanism, a heating module, a heat dissipation module, a conveying mechanism, a heating cover plate mechanism and a control unit, wherein the chip mechanism comprises a chip mounting bracket and a chip 1, the chip 1 is mounted on the chip mounting bracket, the chip 1 comprises a reaction bottom plate and capillary tubes, grooves are formed in the reaction bottom plate, the capillary tubes are arranged in the grooves, and at least two temperature sensors are further arranged on the chip; the chip mechanism is also provided with a heating cover plate mechanism for sealing and heating the chip; the heating cover plate mechanism is arranged on the chip mechanism, the conveying mechanism comprises a movable base 18, and the heating module and the heat dissipation module are arranged on the movable base 18 from top to bottom;
the heating module provided by the invention comprises a first heating area, a second heating area and a third heating area; the first heating area 10, the second heating area 11 and the third heating area 12 respectively comprise a first heat-conducting plate 7, a second heat-conducting plate 20, a primary refrigerating sheet 8 and a secondary refrigerating sheet 9, wherein the first heat-conducting plate 7, the primary refrigerating sheet 8, the second heat-conducting plate 20 and the secondary refrigerating sheet 9 are sequentially arranged from top to bottom; specifically, the first heat conducting plate and the second heat conducting plate can be aluminum plates, wherein the first heat conducting plate, the first-stage refrigerating plate, the second heat conducting plate and the second-stage refrigerating plate can be bonded together by using a heat conducting adhesive;
the heat dissipation module provided by the invention comprises a heat dissipation support 14 and a fan 15, wherein a first heating area 10, a second heating area 11 and a third heating area 12 are sequentially arranged on the heat dissipation support 14 from left to right, and the fan 15 is arranged below the heat dissipation support 14; the control unit can control the power of the fan, so that the heat of the fan, the heat dissipation bracket and the heat dissipation plate can overflow the heat of the heating module under the combined action.
Wherein, a heat dissipation plate 13 is further arranged between the heat dissipation bracket 14 and the fan 15, and a plurality of heat dissipation holes are arranged on the heat dissipation plate 13.
The control unit is used for controlling the heating module, the heating cover plate mechanism and the radiating module to work according to the real-time temperature detected by the temperature sensor; the control unit is used for controlling the operation of the conveying mechanism according to the position of the chip.
In the extension stage, the conveying mechanism control chip 1 is located on the first heat conducting plate of the first heating region, so that the extension stage is reacted in the first heating region 10, in the denaturation stage, the conveying mechanism control chip is located on the first heat conducting plate of the second heating region 11, so that the elongation stage is reacted in the second heating region 12, and in the annealing stage, the conveying mechanism control chip is located on the first heat conducting plate of the third heating region, so that the annealing stage is reacted in the third heating region.
A left isolation block 16 is arranged between the first heating area 10 and the second heating area 11, and a right isolation block 17 is arranged between the second heating area 11 and the third heating area 12. The left isolation block 16 and the right isolation block 17 are used for ensuring that the first heating area, the second heating area and the third heating area move independently and do not interfere with each other, so that the temperature can be accurately controlled.
The chip provided by the invention is also provided with a displacement sensor, the displacement sensor is used for detecting whether the conveying mechanism accurately conveys the chip to the corresponding first heat-conducting plate during the nucleic acid amplification reaction, and the length and the width of the first heat-conducting plate are equal to the length and the width of the bottom of the chip mechanism.
The conveying structure provided by the invention further comprises two fixed bases 19, and the moving base 18 is arranged on the two fixed bases 19. The two fixed bases 19 provided by the invention are respectively provided with a sliding groove, two sides of the moving base 18 are positioned in the sliding grooves, a motor is arranged below the moving base, and the control unit controls the motor to drive the moving base 18 to horizontally move in the sliding grooves.
The heating cover plate mechanism provided by the invention comprises a heating cover plate 2 and a heating cover plate support, wherein an electric heating piece 3 is arranged on the bottom surface of the heating cover plate, the control unit controls the electric heating piece 3 to heat, the heating cover plate support comprises a top cover plate 5 and a side cover plate 6, and the side cover plate 6 is connected to the edge of the top cover plate 5.
Be provided with two bases 4 on the chip mounting support, be provided with the chip mount table on two bases 4, the chip both sides are provided with the screens, the screens difference joint of chip 1 is on the chip mount table, 2 lids of heating apron close in the chip top.
An elastic mechanism can be arranged between the electric heating piece 3 and the chip 1, so that the chip can be prevented from being damaged and crushed.
The control unit provided by the invention is mainly used for heating and/or cooling the chip in the extension and annealing phases by the first-stage refrigerating sheet and the second-stage refrigerating sheet, and at the moment, the heating cover plate mechanism is in a closed state, or the heating power during the extension and annealing phases is lower than that in the denaturation phase; the control unit may control the heating and/or cooling capacity of the primary and secondary cooling fins such that the desired temperature is quickly reached and maintained for the desired time.
In another aspect, the present invention provides a method for controlling heating of a nucleic acid amplification apparatus, comprising the steps of:
s1: the control unit controls the conveying mechanism to convey the chip mechanism to the first heat-conducting plate of the first heating area, the displacement sensor is used for detecting whether the bottom of the chip mechanism corresponds to the first heat-conducting plate of the first heating area, if so, the control unit controls the conveying mechanism to stop, if not, the conveying mechanism continues conveying the chip mechanism until the displacement sensor detects that the bottom of the chip mechanism corresponds to the first heat-conducting plate of the first heating area, and then the control unit controls the first heating area to heat until the temperature T1 set in the first heating area is reached and the expected time T1 is kept;
s2: after the temperature is kept for T1 time at the temperature of T1 in the first heating area, the control unit controls the conveying mechanism to convey the chip mechanism to the first heat-conducting plate of the second heating area, and the displacement sensor is used for detecting whether the bottom of the chip mechanism corresponds to the first heat-conducting plate of the second heating area or not, if so, the control unit controls the conveying mechanism to stop, and if not, the conveying mechanism continues to convey the chip mechanism until the displacement sensor detects that the bottom of the chip mechanism corresponds to the first heat-conducting plate of the second heating area; the control unit controls the heating of the second heating area, and if the temperature T2 set by the second heating area is not reached after the expected time T2, the control unit controls the heating cover plate mechanism to heat until the temperature T2 set by the second heating area is reached and the expected time T3 is kept;
s3: after keeping at the temperature of the second heating zone T2 for T3 time, the control unit turns off the heat source of the heating cover plate mechanism;
s4: the control unit controls the conveying mechanism to convey the chip mechanism to the first heat-conducting plate of the third heating area, the displacement sensor is used for detecting whether the bottom of the chip mechanism corresponds to the first heat-conducting plate of the third heating area, if so, the conveying mechanism is controlled to stop through the control unit, and if not, the conveying mechanism continues to convey the chip mechanism until the displacement sensor detects that the bottom of the chip mechanism corresponds to the first heat-conducting plate of the third heating area; the control unit controls the power of the fan according to the temperature displayed by the temperature sensor on the chip, if the temperature displayed by the temperature sensor is far greater than the temperature T3 set by the third heating area, the power of the fan is increased, and if the temperature displayed by the temperature sensor is lower than the temperature T3 set by the third heating area, the control unit controls the third heating area to heat until the desired time T4 is kept.
In the extension reaction stage, that is, when the chip mechanism is in the first heating region, if the temperature of the temperature sensor is far lower than the set temperature T1 within the expected time, the control unit may control the heating cover plate mechanism to heat until the temperature rises to T1;
in the annealing reaction stage, that is, when the chip mechanism is in the third heating region, if the temperature of the temperature sensor is far lower than the set temperature T3 in the expected time, the control unit may control the heating cover plate mechanism to heat until the temperature rises to T3;
the above description is only an example of the present invention, and not intended to limit the scope of the present invention, and all modifications of equivalent structures and equivalent processes, which are made by using the contents of the present specification and the accompanying drawings, or directly or indirectly applied to other related technical fields, are included in the scope of the present invention.
Claims (10)
1. A heating control device of a nucleic acid amplification instrument is characterized by comprising a chip mechanism, a heating module, a heat dissipation module, a conveying mechanism, a heating cover plate mechanism and a control unit, wherein the chip mechanism comprises a chip mounting support and a chip, the chip is mounted on the chip mounting support, the chip comprises a reaction bottom plate and capillary tubes, grooves are formed in the reaction bottom plate, the capillary tubes are arranged in the grooves, and at least two temperature sensors are further arranged on the chip; the chip mechanism is also provided with a heating cover plate mechanism for sealing and heating the chip; the heating cover plate mechanism is arranged on the chip mechanism, the conveying mechanism comprises a moving base, and the heating module and the heat dissipation module are arranged on the moving base from top to bottom;
the heating module comprises a first heating area, a second heating area and a third heating area; the first heating area, the second heating area and the third heating area respectively comprise a first heat-conducting plate, a second heat-conducting plate, a first-stage refrigerating sheet and a second-stage refrigerating sheet, and the first heat-conducting plate, the first-stage refrigerating sheet, the second heat-conducting plate and the second-stage refrigerating sheet are sequentially arranged from top to bottom;
the heat dissipation module comprises a heat dissipation support and a fan, the first heating area, the second heating area and the third heating area are sequentially arranged on the heat dissipation support from left to right, and the fan is arranged below the heat dissipation support;
the control unit is used for controlling the heating module, the heating cover plate mechanism and the radiating module to work according to the real-time temperature detected by the temperature sensor; the control unit is used for controlling the operation of the conveying mechanism according to the position of the chip.
2. The heating control device of the nucleic acid amplification instrument according to claim 1, wherein a heat dissipation plate is further disposed between the heat dissipation bracket and the fan, and the heat dissipation plate is provided with a plurality of heat dissipation holes.
3. The heating control device for the nucleic acid amplification apparatus according to claim 1, wherein the conveying mechanism control chip is located on the first heat-conducting plate of the first heating region in the extension stage, the conveying mechanism control chip is located on the first heat-conducting plate of the second heating region in the denaturation stage, and the conveying mechanism control chip is located on the first heat-conducting plate of the third heating region in the annealing stage.
4. The heating control device for the nucleic acid amplification apparatus according to claim 1, wherein a left spacer is provided between the first heating region and the second heating region, and a right spacer is provided between the second heating region and the third heating region.
5. The heating control device of the nucleic acid amplification instrument according to claim 1, wherein the chip is further provided with a displacement sensor for detecting whether the conveying mechanism accurately conveys the chip to the corresponding first heat-conducting plate during the nucleic acid amplification reaction, and the length and width of the first heat-conducting plate are equal to the length and width of the bottom of the chip mechanism.
6. The heating control device of the nucleic acid amplification apparatus according to claim 1, wherein the transfer structure further comprises two fixed bases, and the movable base is mounted on the two fixed bases.
7. The heating control device of the nucleic acid amplification instrument according to claim 6, wherein the two fixing bases are provided with sliding grooves, two sides of the moving base are located in the sliding grooves, a motor is arranged below the moving base, and the control unit controls the motor to drive the moving base to move horizontally in the sliding grooves.
8. The heating control device of the nucleic acid amplification apparatus of claim 1, wherein the heating cover plate mechanism comprises a heating cover plate and a heating cover plate support, the bottom surface of the heating cover plate is provided with an electric heating plate, the control unit controls the electric heating plate to heat, and the heating cover plate support comprises a top cover plate and a side cover plate, and the side cover plate is connected to the edge of the top cover plate.
9. The heating control device of the nucleic acid amplification instrument according to claim 8, wherein the chip mounting bracket is provided with two bases, the two bases are provided with chip mounting platforms, clamping positions are arranged on two sides of the chip, the clamping positions of the chip are respectively clamped on the chip mounting platforms, and the heating cover plate covers the chip.
10. A method for controlling the heating of a nucleic acid amplification apparatus using the heating control device for a nucleic acid amplification apparatus according to any one of claims 1 to 8, comprising the steps of:
s1: the control unit controls the conveying mechanism to convey the chip mechanism to the first heat-conducting plate of the first heating area, the displacement sensor is used for detecting whether the bottom of the chip mechanism corresponds to the first heat-conducting plate of the first heating area, if so, the control unit controls the conveying mechanism to stop, if not, the conveying mechanism continues conveying the chip mechanism until the displacement sensor detects that the bottom of the chip mechanism corresponds to the first heat-conducting plate of the first heating area, and then the control unit controls the first heating area to heat until the temperature T1 set in the first heating area is reached and the expected time T1 is kept;
s2: after the temperature is kept for T1 time at the temperature of T1 in the first heating area, the control unit controls the conveying mechanism to convey the chip mechanism to the first heat-conducting plate of the second heating area, and the displacement sensor is used for detecting whether the bottom of the chip mechanism corresponds to the first heat-conducting plate of the second heating area or not, if so, the control unit controls the conveying mechanism to stop, and if not, the conveying mechanism continues to convey the chip mechanism until the displacement sensor detects that the bottom of the chip mechanism corresponds to the first heat-conducting plate of the second heating area; the control unit controls the heating of the second heating area, and if the temperature T2 set by the second heating area is not reached after the expected time T2, the control unit controls the heating cover plate mechanism to heat until the temperature T2 set by the second heating area is reached and the expected time T3 is kept;
s3: after keeping at the temperature of the second heating zone T2 for T3 time, the control unit turns off the heat source of the heating cover plate mechanism;
s4: the control unit controls the conveying mechanism to convey the chip mechanism to the first heat-conducting plate of the third heating area, the displacement sensor is used for detecting whether the bottom of the chip mechanism corresponds to the first heat-conducting plate of the third heating area, if so, the conveying mechanism is controlled to stop through the control unit, and if not, the conveying mechanism continues to convey the chip mechanism until the displacement sensor detects that the bottom of the chip mechanism corresponds to the first heat-conducting plate of the third heating area; the control unit controls the power of the fan according to the temperature displayed by the temperature sensor on the chip, if the temperature displayed by the temperature sensor is far greater than the temperature T3 set by the third heating area, the power of the fan is increased, and if the temperature displayed by the temperature sensor is lower than the temperature T3 set by the third heating area, the control unit controls the third heating area to heat until the desired time T4 is kept.
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