CN114812005B

CN114812005B - Active rapid heat dissipation method and device of thermal cycler based on thermoelectric refrigeration piece

Info

Publication number: CN114812005B
Application number: CN202210738155.XA
Authority: CN
Inventors: 李清宁
Original assignee: Hefei Zhongke Guoteng Biotechnology Co ltd
Current assignee: Hefei Zhongke Guoteng Biotechnology Co ltd
Priority date: 2022-06-28
Filing date: 2022-06-28
Publication date: 2022-10-11
Anticipated expiration: 2042-06-28
Also published as: CN114812005A

Abstract

The invention discloses a method and a device for actively and quickly radiating heat of a thermal cycler based on thermoelectric refrigeration sheets.A thermal block thermoelectric refrigeration sheet of the thermal cycler is provided with an active quick radiating module for actively radiating heat of the thermal block thermoelectric refrigeration sheet; the heat dissipation VC temperature equalizing plate acts on the hot block thermoelectric refrigerating piece, and the heat dissipation refrigerating piece actively adjusts the temperature difference delta T between the upper surface and the lower surface of the hot block thermoelectric refrigerating piece to be kept in a preset value range under the control of a temperature controller of temperature control software with a specific logic algorithm, so that the hot block thermoelectric refrigerating piece is ensured to keep larger output heat; the active rapid heat dissipation module adopts liquid metal, a VC temperature equalizing plate with condensate sealed inside and a heat pipe radiator. The invention relates to a method and a device for actively and quickly radiating heat of a thermal cycler based on thermoelectric refrigerating sheets, which adopt a technology and a device for actively controlling the temperature change rate of temperature rise and temperature drop in the thermal cycle process and quickly radiating heat of a thermal cycle execution unit, thereby realizing the purpose of quick PCR thermal cycle.

Description

Active rapid heat dissipation method and device of thermal cycler based on thermoelectric refrigeration piece

Technical Field

The invention relates to the technical field of heat dissipation, in particular to a method and a device for actively and quickly dissipating heat of a thermal cycler based on thermoelectric refrigeration sheets.

Background

The amplification PCR is an English abbreviation of nucleic acid Polymerase Chain Reaction (Polymerase Chain Reaction), and the PCR Reaction conditions are temperature, time and cycle number. The denaturation-annealing-extension 3 temperature points were set based on the three steps of the PCR principle. In a standard reaction, double-stranded DNA is denatured at 90 to 95 ℃, then is rapidly cooled to 40 to 60 ℃, a primer is annealed and is combined to a target sequence, then is rapidly heated to 70 to 75 ℃, and a primer chain is extended along a template under the action of TaqDNA polymerase. The PCR reaction is realized by thermal cycling of denaturation-annealing-extension, and 30-40 continuous thermal cycles are usually required for one PCR amplification experiment. The time required for each temperature change directly affects the total time of the PCR reaction. The temperature rise and fall rate between different temperature areas in PCR thermal cycle is improved, the time required by the whole PCR amplification process can be shortened, and the specificity of the nucleic acid amplification result can be improved.

The PCR thermal cycler is generally composed of a heat-sealing part, a thermal cycling part, a control part, and a power supply part. The thermal cycle part is used for realizing the temperature rise and fall control in the control process. PCR thermal cyclers typically employ thermoelectric cooling fins and metal PCR thermal blocks as thermal cycling components. The thermoelectric refrigeration piece provides a special heat source of thermal cycle. When current passes through the thermoelectric refrigerating piece, heat transfer is generated between the two end faces of the thermoelectric refrigerating piece, the heat is transferred from one end face to the other end face, a temperature difference delta T is generated between the two end faces of the thermoelectric refrigerating piece, and a cold end face and a hot end face are formed. As the time of the voltage or current action is prolonged, the temperature difference delta T between two end faces of the thermoelectric refrigerating chip is increased, the output heat quantity is reduced, and the temperature rising and falling speed of the PCR thermal cycle is reduced.

Particularly, in the cooling stage of the thermal cycle, the heat of the thermoelectric refrigeration piece includes the heat generated by the refrigeration of the thermoelectric refrigeration piece besides the heat absorbed by the cold end, if the superposed heat cannot be quickly dissipated, the temperature of the cold end surface is difficult to drop, and the cooling rate of the thermal cycle is reduced, which is one of the reasons that the cooling rate of the thermoelectric refrigeration piece is obviously lower than the heating rate.

The temperature control part adopting PID control controls the temperature of the thermal block thermoelectric refrigerating piece, single PID control only controls the temperature T0 of the thermal block by controlling the output heat of the thermal block thermoelectric refrigerating piece, but the temperature difference delta T at two ends of the thermal block thermoelectric refrigerating piece is increased along with the rise of the temperature T0 of the thermal block, the output heat is reduced due to the characteristics of the thermal block thermoelectric refrigerating piece, and the temperature rise rate of the thermal block temperature T0 is reduced.

The thermal interface between the thermal cycle execution unit and the heat dissipation unit of the PCR thermal cycler usually adopts a heat-conducting silicone grease or graphite film as a heat-conducting medium. The highest heat conductivity coefficient of the heat-conducting silicone grease can only reach 11W/m.K at present. Due to the structure of the graphite film, the heat conductivity coefficient of the surface of the graphite film is 180W/m.K. However, the thermal conductivity between the surfaces (in the thickness direction) is only about 5W/mK. The 'thermal barrier' bottleneck causes that the heating or refrigerating capacity of the thermal block thermoelectric refrigerating sheet is difficult to be quickly transferred to the VC temperature equalizing plate and the heat radiating module of the PCR thermal block, and the temperature change rate of the fixed thermal cycler is directly influenced. The heat conductivity coefficient of the liquid metal can reach 73W/m.K, which is several times of that of the traditional silicone grease or graphite film, and the liquid metal medium is used as a heat conducting agent, reduces the thermal resistance of a thermal interface and realizes rapid heat conduction.

The heat sink of the fixed PCR thermal cycler is usually made of a material with high thermal conductivity, such as copper, aluminum, and stainless steel. However, these materials have a relatively low specific heat capacity, i.e., they absorb less heat per unit temperature and do not quickly conduct much heat. VC (Vapor Chambers) Vapor Chambers and heat pipes use evaporation and condensation of a liquid sealed within a metal envelope to transport heat, use liquid-Vapor two-phase heat transfer to move heat quickly within the assembly, with the heat transfer being 10 to 50 times higher than solid metal structures to improve their overall thermal performance. Heat pipes move heat primarily on the axis of the pipe, connecting the heat source to the ideal choice of distal fins, especially for relatively tortuous paths; the VC temperature equalizing plate diffuses heat to the whole plane, so that the temperature of the whole plane is more uniform, the heat uniformity of the whole plane is improved, the heat resistance of a thermal interface is reduced by the VC temperature equalizing plate and the liquid metal medium, and the rapid heat conduction is realized.

Disclosure of Invention

The invention aims to avoid the defects in the prior art, and provides an active rapid heat dissipation method and device for a thermal cycler based on a thermoelectric cooling plate, so that the temperature rise and fall rate of a thermal cycle execution unit of the PCR thermal cycler can be improved, and the time of a single PCR amplification experiment can be shortened.

The invention adopts the following technical scheme to solve the technical problem.

A thermal cycler active rapid heat dissipation method based on thermoelectric refrigeration sheets is used for actively dissipating heat of a thermal block thermoelectric refrigeration sheet of a thermal cycler;

the active rapid heat dissipation method of the thermal cycler comprises the following steps:

step 1: arranging an active quick heat dissipation device for actively dissipating heat of a hot block thermoelectric refrigerating piece on the hot block thermoelectric refrigerating piece, so that one side of a heat dissipation VC temperature equalizing plate of the active quick heat dissipation device is attached to the hot block thermoelectric refrigerating piece;

step 2: at least one heat dissipation thermoelectric refrigerating sheet is attached to the other side of the heat dissipation VC temperature-equalizing plate;

and step 3: through heat dissipation thermoelectric refrigeration piece heats up or cools down for heat dissipation VC samming board can heat up or cool down for hot block thermoelectric refrigeration piece, and then makes the difference in temperature delta T between the upper surface and the lower surface of hot block thermoelectric refrigeration piece remain in the predetermined value territory throughout, ensures that hot block thermoelectric refrigeration piece is in best operating condition.

The invention relates to a thermal cycler active rapid heat dissipation method based on thermoelectric refrigeration sheets, which is also characterized in that:

preferably, the thermal block thermoelectric refrigeration piece and the active rapid heat dissipation device are both connected with a temperature controller;

the temperature controller is used for controlling the thermal block thermoelectric refrigerating piece to heat or cool the thermal block thermoelectric refrigerating piece;

the temperature controller is used for controlling the active quick heat dissipation device, so that the heat dissipation thermoelectric refrigerating sheet of the active quick heat dissipation device is heated or cooled.

Preferably, the temperature controller is internally provided with a temperature control program, and the temperature control program is used for executing a temperature control algorithm.

Preferably, the temperature control algorithm comprises a cascade PID control algorithm.

Preferably, in the temperature control algorithm, before the thermal block thermoelectric refrigerating sheet needs to cool the thermal block VC temperature-equalizing plate of the PCR thermal cycler, the thermal block VC temperature-equalizing plate is actively cooled in advance by the thermal block thermoelectric refrigerating sheet.

Preferably, in the temperature control algorithm, when the thermal block thermoelectric refrigeration piece needs to heat up the thermal block VC temperature-equalizing plate, the heat-dissipating VC temperature-equalizing plate of the active rapid heat-dissipating device and the thermal block VC temperature-equalizing plate are controlled to heat up synchronously, so that the temperature difference Δ T between the upper and lower surfaces of the thermal block thermoelectric refrigeration piece is within a predetermined value range.

Preferably, in the temperature control algorithm, at least one set of temperature control PID values is set for each variable temperature node of the PCR thermal cycle.

In addition, the invention also discloses a thermocycler active type quick heat dissipation device based on the thermoelectric refrigeration piece, which is characterized in that the active type quick heat dissipation device is arranged on the thermoelectric refrigeration piece of the thermal block as a heat-dissipated object and is used for keeping the temperature difference delta T between the upper surface and the lower surface of the thermoelectric refrigeration piece of the thermal block in a preset value range all the time;

the active rapid heat dissipation device comprises at least one heat dissipation VC temperature equalizing plate, at least one heat dissipation thermoelectric refrigerating sheet, a liquid metal medium, a conduction type heat radiator and a convection type heat radiator.

Preferably, the heat dissipation VC temperature-equalizing plate and the hot block thermoelectric refrigerating piece exchange heat, and the heat dissipation VC temperature-equalizing plate and the hot block thermoelectric refrigerating piece conduct rapid heat conduction through the liquid metal medium;

the heat dissipation VC temperature-equalizing plate is in heat exchange with the heat dissipation thermoelectric refrigerating sheet, and the heat dissipation VC temperature-equalizing plate and the heat dissipation thermoelectric refrigerating sheet are in rapid heat conduction through the liquid metal medium;

a liquid metal medium is arranged between the heat dissipation thermoelectric refrigeration piece and the conduction type radiator, and rapid heat conduction is carried out between the heat dissipation thermoelectric refrigeration piece and the conduction type radiator through the liquid metal medium.

Preferably, the liquid metal medium includes, but is not limited to, a liquid metal heat conducting agent, a liquid metal alloy, a liquid metal heat conducting paste, a liquid metal heat conducting glue, or a phase-change liquid metal alloy sheet.

Preferably, the condensing agent sealed inside the heat dissipation VC temperature equalization plate comprises but is not limited to water, ethanol, methanol, acetone or butane.

Preferably, the active rapid heat dissipation device of the thermal cycler based on the thermoelectric refrigeration piece further comprises a temperature controller; and the temperature controller is connected with a temperature sensor of the heat dissipation VC temperature equalizing plate, the hot block thermoelectric refrigerating sheet and the heat dissipation thermoelectric refrigerating sheet.

The invention also discloses an electronic device, comprising: at least one processor and a memory communicatively coupled to the at least one processor;

wherein the memory stores instructions executable by the at least one processor to enable the at least one processor to perform the above-described method for active rapid thermal cycler cooling based on thermoelectric cooling fins.

The invention also discloses a computer readable storage medium, wherein a computer program is stored, and when the computer program is executed by a processor, the active rapid heat dissipation method of the thermal cycler based on the thermoelectric cooling fins is realized.

Compared with the prior art, the invention has the beneficial effects that:

the invention discloses an active rapid heat dissipation method and device for a thermal cycler based on a thermoelectric refrigeration piece, which are suitable for a PCR thermal cycler based on the thermoelectric refrigeration piece, and comprise a thermal cycle execution unit for a nucleic acid amplification instrument to dissipate heat rapidly; the thermal cycle execution unit of the nucleic acid amplification instrument comprises a PCR hot block VC temperature-equalizing plate, a liquid metal medium of the PCR hot block VC temperature-equalizing plate and a hot block thermoelectric refrigerating sheet; an active rapid heat dissipation device is arranged on the hot block thermoelectric refrigerating piece and used for enabling the temperature difference delta T between the upper surface and the lower surface of the hot block thermoelectric refrigerating piece to be kept within a preset value range all the time; the heat cycle execution unit and the active quick heat dissipation device are both connected with a temperature controller, and the temperature controller is used for controlling the heat cycle execution unit and the active quick heat dissipation device.

In the prior art, the thermal cycle temperature rise and fall rate of a mainstream PCR tube nucleic acid amplification PCR instrument product is generally 4 ℃/second for temperature rise and 3 ℃/second for temperature fall; some high-end products are heated up by 6 ℃/s and cooled down by 4 ℃/s.

The sample machine of the PCR tube nucleic acid amplification PCR instrument adopting the active rapid heat dissipation technical scheme has the advantages that the temperature is increased by 8 ℃/s and reduced by 6 ℃/s, and the temperature increasing and reducing rate is 2 times of the mainstream product in the prior art and is 1.5 times of the high-end product.

The sample machine of the nucleic acid amplification PCR instrument with the fixed PCR cavity microfluidic chip achieves the levels of temperature rise of 12 ℃/second and temperature drop of 10 ℃/second, and the temperature rise and fall rate is more than 3 times of that of a mainstream product in the prior art and more than 2 times of that of a high-end product. Fig. 13 is a graph of temperature rise and fall, where the absolute value of the slope of the curve of temperature rise and fall is the rate of temperature rise and fall.

The invention is used for heat dissipation of circuit boards or electronic devices of various experimental instruments and detection instruments, and is particularly suitable for life science instruments and medical instruments.

The active rapid heat dissipation method and device for the thermal cycler based on the thermoelectric refrigeration piece can ensure that the thermal cycle execution unit of the nucleic acid amplification instrument rapidly dissipates heat, improve the temperature change rate of temperature rise and temperature reduction in the thermal cycle process, and realize rapid heat transfer to the thermal cycle execution module, thereby shortening the overall time of thermal cycle and the like.

Drawings

Fig. 1 is a schematic block diagram of a thermal cycler active fast heat sink based on thermoelectric cooling fins according to the present invention.

Fig. 2 is a control schematic block diagram of a control algorithm of the active rapid heat dissipation method of the thermal cycler based on the thermoelectric cooling fins.

Fig. 3 is a front view of a first embodiment of a thermal cycler active quick heat sink based on thermoelectric cooling fins in accordance with the present invention.

Fig. 4 isbase:Sub>A sectional viewbase:Sub>A-base:Sub>A of fig. 3.

Fig. 5 is an exploded view of fig. 3.

Fig. 6 is a front view of a second embodiment of a thermal cycler active quick heat sink based on thermoelectric cooling fins in accordance with the present invention.

Fig. 7 is a sectional view taken along line B-B of fig. 6.

Fig. 8 is an exploded view of fig. 6.

FIG. 9 is a graph illustrating the effect of controlling the temperature gradient in 8 channels in one embodiment.

Fig. 10 is a front view of a third embodiment of a thermal cycler active fast heat sink based on thermoelectric cooling fins of the present invention.

Fig. 11 is a cross-sectional view C-C of fig. 10.

Fig. 12 is an exploded view of fig. 10.

Fig. 13 is a graph of temperature rise and fall.

The present invention will be further described with reference to the following detailed description and accompanying drawings.

Detailed Description

Referring to fig. 1 to 12, the present invention provides a method for actively and rapidly dissipating heat of a thermal cycler based on thermoelectric cooling fins, which is used for actively dissipating heat of a thermal block thermoelectric cooling fin 120 of the thermal cycler;

step 1: arranging an active quick heat dissipation device for actively dissipating heat of the hot block thermoelectric refrigerating fins 120 on the hot block thermoelectric refrigerating fins 120, so that one side of a heat dissipation VC (temperature uniformity) plate 210 of the active quick heat dissipation device is attached to the hot block thermoelectric refrigerating fins 120;

step 2: at least one heat dissipation thermoelectric refrigerating sheet 220 is attached to the other side of the heat dissipation VC temperature-equalizing plate 210;

and step 3: through the heat dissipation thermoelectric refrigeration piece 220 heats up or cools down for the heat dissipation VC temperature equalizing plate 210, make the heat dissipation VC temperature equalizing plate 210 can heat up or cool down for the hot block thermoelectric refrigeration piece 120, and then make the difference in temperature delta T between the upper surface and the lower surface of hot block thermoelectric refrigeration piece 120 remain in the predetermined value territory all the time, ensure that hot block thermoelectric refrigeration piece 120 is in the best operating condition.

In specific implementation, the thermal block thermoelectric refrigeration chip 120 and the active fast heat dissipation device are both connected to a temperature controller;

an active rapid heat dissipation device for actively dissipating heat of the thermal block thermoelectric refrigeration piece 120 is arranged on the thermal block thermoelectric refrigeration piece 120; the active rapid heat dissipation device comprises a heat dissipation VC temperature-equalizing plate 210 and at least one heat dissipation thermoelectric refrigerating sheet 220; the heat dissipation VC temperature-uniforming plate 210 is attached to the hot block thermoelectric refrigeration sheet 120, and the heat dissipation thermoelectric refrigeration sheet 220 is attached to the heat dissipation VC temperature-uniforming plate 210;

the temperature controller is used for controlling the thermal block thermoelectric refrigerating sheet 120 to heat or cool the thermal block thermoelectric refrigerating sheet 120;

the temperature controller is used for controlling the active fast heat dissipation device, so that the heat dissipation thermoelectric refrigeration piece 220 of the active fast heat dissipation device is heated up or cooled down.

In the invention, the predetermined value range is 2-10 ℃. The temperature difference between the cold end face and the hot end face of the thermal block thermoelectric cooling piece 120 is within the range of 2-10 ℃, so that the thermal block thermoelectric cooling piece can be ensured to be in the optimal working state, namely the thermal block thermoelectric cooling piece 120 is ensured to work in a stable and large heat output mode, and the thermal block thermoelectric cooling piece can work at a large temperature change rate.

The temperature controller collects the actual temperature T0 of the heat block VC temperature equalizing plate 110 and the actual temperature T1 of the heat dissipation VC temperature equalizing plate through temperature sensors respectively arranged on the heat block VC temperature equalizing plate 110 and the heat dissipation VC temperature equalizing plate 210 of the PCR thermal cycle, and controls the heat output of the heat block thermoelectric refrigerating sheet 120 and the heat dissipation thermoelectric refrigerating sheet 220 through a temperature control program with a specific logic algorithm built in the temperature controller.

The heat dissipation thermoelectric refrigeration piece 220 actively controls the actual temperature T1 of the heat dissipation VC temperature-equalizing plate through the temperature controller and the temperature sensor, so that the temperature difference delta T between the actual temperature T0 of the heat dissipation VC temperature-equalizing plate and the actual temperature T0 of the heat block VC temperature-equalizing plate 110 is kept within a preset value range of 2-10 ℃, and the heat block thermoelectric refrigeration piece 120 is ensured to output stable and large heat, so that the rapid temperature change of the PCR thermal cycler is realized. The calculation formula of the temperature difference delta T is as follows: Δ T = T1-T0.

In fig. 1, the object of the refrigeration of the method and apparatus of the present invention is a PCR thermal cycle execution module. The PCR thermal cycle execution module comprises at least one thermal block VC temperature-equalizing plate 110 positioned at the uppermost part, a liquid metal medium conductor is arranged below the thermal block VC temperature-equalizing plate 110, and a thermal block thermoelectric refrigerating sheet 120 is arranged below the liquid metal medium conductor. Referring to fig. 1, the present invention includes an active rapid heat sink and a temperature controller (solid line portion in fig. 1) which are thermally conductive with a thermal cycle execution module (dotted line portion in fig. 1) which is a heat-dissipated object.

As can be seen from fig. 1, the upper end surface of the thermal block thermoelectric cooling plate 120 is attached to the thermal block VC temperature-equalizing plate 110 through the liquid metal medium, and since the heat conduction speed of the liquid metal medium is very high, the temperature of the upper end surface of the thermal block thermoelectric cooling plate 120 is substantially the same as the actual temperature T0 of the thermal block VC temperature-equalizing plate 110; therefore, T0 can be measured by the temperature sensor disposed on the thermal block VC temperature equalizing plate 110, and the temperature of the upper end surface of the thermal block thermoelectric cooling fins 120 can be obtained. In specific implementation, the upper end surface of the thermal block thermoelectric cooling plate 120 is determined as T0.

Similarly, the lower end surface of the thermal block thermoelectric cooling plate 120 is attached to the heat dissipation VC temperature-equalizing plate 210 through a liquid metal medium, so the temperature of the lower end surface of the thermal block thermoelectric cooling plate 120 is substantially the same as the actual temperature T1 of the heat dissipation VC temperature-equalizing plate 210; therefore, T1 can be measured by the temperature sensor disposed on the heat dissipating VC temperature equalizing plate 210, and the temperature of the lower end surface of the thermal block thermoelectric cooling fins 120 is obtained. In specific implementation, the lower end surface of the thermal block thermoelectric cooling plate 120 is determined as T1.

In specific implementation, a temperature control program is built in the temperature controller, and the temperature control program is used for executing a temperature control algorithm.

In specific implementation, the temperature control algorithm includes, but is not limited to, a cascade PID control algorithm; a fuzzy PID control algorithm or an intelligent PID control algorithm may also be selected.

In the temperature control algorithm, when the thermal block thermoelectric refrigerating sheet needs to cool the thermal block VC temperature-equalizing plate of the PCR thermal cycler, the thermal block VC temperature-equalizing plate is actively cooled in advance through the thermal block thermoelectric refrigerating sheet.

In the temperature control algorithm, when the thermal block thermoelectric refrigeration piece needs to be heated up by the thermal block VC temperature-equalizing plate, the heat dissipation VC temperature-equalizing plate of the active rapid heat dissipation device and the thermal block VC temperature-equalizing plate are controlled to be heated up synchronously, so that the temperature difference Δ T between the upper surface and the lower surface of the thermal block thermoelectric refrigeration piece is within a predetermined value range.

In specific implementation, at least one group of temperature control PID values is set for each variable temperature node of the PCR thermal cycle in the temperature control algorithm.

As shown in FIG. 2, the specific logic algorithm control software employs cascaded PID control. In FIG. 2: the PID control cycle of the thermal block VC temperature-equalizing plate of the PCR thermal cycle is a main control cycle (outer cycle in figure 1), the temperature T0 of the thermal block VC temperature-equalizing plate 110 is a main object, and a cascade PID control main control cycle loop is formed by the thermal block VC temperature-equalizing plate temperature T0 sensor and the thermal block VC temperature-equalizing plate temperature T0 sensor; the heat dissipation PID controller is an auxiliary control loop (an inner loop in fig. 2), the heat dissipation temperature T1 is an auxiliary object, and the heat dissipation temperature T1 sensor form an auxiliary loop of cascade PID control; in the general PID control of the VC temperature equalization plate of the PCR thermal block, the PID control controls the working current and the output heat of the thermoelectric cooling fins 120 of the thermal block through PWM pulse width modulation, thereby controlling the temperature T0 of the VC temperature equalization plate of the PCR thermal block.

However, as the temperature T0 of the VC temperature-equalizing plate 110 of the thermal block rises, the temperature difference Δ T between the upper and lower end surfaces of the thermal block thermoelectric cooling fins 120 decreases, and the output heat decreases accordingly, resulting in a decrease in the temperature change rate of the VC temperature-equalizing plate of the PCR thermal block. The method adopts cascade PID control, namely a heat dissipation PID controller is connected in series as a secondary controller, a heat dissipation temperature T1 directly related to the back temperature of a hot block thermoelectric refrigerating piece is taken as a secondary object, the working current and the output heat of the heat dissipation thermoelectric refrigerating piece are cooperatively driven and controlled, the temperature difference between two end faces of the hot block thermoelectric refrigerating piece is kept within the range of 2-10 ℃, the hot block thermoelectric refrigerating piece is ensured to be in the optimal heat output state, and the temperature change rate of the temperature T0 of the VC temperature equalizing plate of the PCR hot block is improved.

The invention also discloses a thermocycler active quick heat dissipation device based on the thermoelectric refrigeration piece, which is characterized in that the active quick heat dissipation device is arranged on the thermoelectric refrigeration piece 120 of the thermal block as a heat-dissipated object and is used for keeping the temperature difference delta T between the upper surface and the lower surface of the thermoelectric refrigeration piece 120 of the thermal block in a preset value range all the time;

the active fast heat dissipation device comprises at least one heat dissipation VC temperature equalization plate 210, at least one heat dissipation thermoelectric cooling fins 220, a liquid metal medium 230, a conductive heat sink, and a convective heat sink.

The conductive heat sink is a heat pipe heat sink 240. The active fast heat dissipation device comprises at least one heat pipe radiator, and the heat pipe radiator comprises at least one heat pipe.

The convection type heat sink is a heat dissipation fan 250, and is used for dissipating heat of the heat pipe heat sink 240 in an air cooling manner. At least one cooling fan is arranged on the side surface of the cooling fin of the heat pipe radiator.

The heat pipe radiator and the heat radiation fan are adopted in the embodiment to conduct heat and radiate heat, and liquid metal media are adopted between heat conduction interfaces to conduct heat rapidly. The heat dissipation fan is arranged at the heat dissipation fins of the heat pipe radiator, the heat dissipation fins of the heat pipe radiator are cooled or heated through air circulation, and finally the heat pipe radiator is cooled or heated, so that the heat dissipation thermoelectric refrigerating piece is in the best working state. One end of the heat pipe is in thermal contact with the heat dissipation thermoelectric refrigerating sheet through a heat pipe heat dissipation seat, and the other end of the heat pipe can be in thermal contact with at least one heat dissipation fin and can also be in thermal contact with a heat dissipation metal block; the heat on the end face of the heat dissipation thermoelectric refrigerating piece is quickly and axially conducted through steam flow and liquid flow on the inner wall of the heat pipe;

the heat pipe radiator, the heat dissipation electric refrigeration sheet and the heat dissipation VC temperature equalizing plate are sequentially arranged from bottom to top, and liquid metal media are arranged on thermal interfaces among all the components.

In specific implementation, the heat dissipation VC temperature-equalizing plate 210 and the hot block thermoelectric cooling fins 120 perform heat exchange, and the heat dissipation VC temperature-equalizing plate 210 and the hot block thermoelectric cooling fins 120 perform rapid heat conduction through the liquid metal medium 230;

the heat dissipation VC temperature equalizing plate 210 and the heat dissipation thermoelectric cooling fins 220 perform heat exchange, and the heat dissipation VC temperature equalizing plate 210 and the heat dissipation thermoelectric cooling fins 220 perform rapid heat conduction through the liquid metal medium 230;

a liquid metal medium 230 is arranged between the heat dissipation thermoelectric refrigeration sheet 220 and the conductive heat sink, and the heat dissipation thermoelectric refrigeration sheet 220 and the conductive heat sink are rapidly thermally conducted through the liquid metal medium 230.

In specific implementation, the liquid metal medium 230 includes, but is not limited to, a liquid metal heat conducting agent, a liquid metal alloy, a liquid metal heat conducting paste, a liquid metal heat conducting glue, or a phase-change liquid metal alloy sheet, and any one of them may be selected as the liquid metal medium in specific implementation.

The liquid metal medium 230 has a phase transition temperature of less than 30 ℃, a proper viscosity and good wettability with an interface material, and a sealing ring is adopted to effectively prevent the liquid metal from overflowing.

The liquid metal medium is placed between two adjacent thermal interfaces in the active rapid heat dissipation device. The liquid metal medium has higher heat conductivity coefficient, which is beneficial to reducing the thermal resistance of each thermal interface and realizing the quick heat conduction of each thermal interface; the liquid metal medium is between 0.1mm and 0.5mm, and is not limited to the liquid metal heat-conducting agent, the liquid metal heat-conducting paste and the phase-change liquid metal sheet, and the liquid metal medium adopted in the embodiment has the phase-change temperature of less than 30 ℃, proper viscosity and good wettability with an interface material, and can effectively prevent the liquid metal from overflowing.

In specific implementation, the condensing agent sealed inside the heat dissipation VC temperature equalization plate 210 includes, but is not limited to, water, ethanol, methanol, acetone, or butane, and any one of them may be selected as the condensing agent in specific implementation.

Condensing agents are sealed in the steam cavity of the heat dissipation VC temperature equalizing plate 210 and the heat pipe inside of the heat pipe radiator 240.

The heat dissipation VC temperature equalization plate comprises at least one steam cavity, and a shell of the steam cavity is made of metals such as but not limited to copper, aluminum, stainless steel and the like. The heat dissipation VC temperature equalizing plate realizes quick and uniform heat dissipation on the end surface of the thermoelectric refrigerating piece of the heat block by utilizing high-conduction heat of vaporization and condensation; the condensing agents sealed in the vapor cavity of the heat dissipation VC temperature equalization plate 210 and the heat pipe of the heat pipe radiator 240 include, but are not limited to, water (boiling point 100 ℃), ethanol (boiling point 78.3 ℃), methanol (boiling point 64.8 ℃), acetone (boiling point 56.53 ℃), butane, or other refrigerant liquids, and liquids with different boiling points are used for heat conduction at different temperatures; the heat dissipation VC temperature equalization plate is usually made of a metal material with high thermal conductivity, and usually includes metal materials such as gold, silver, copper, aluminum, etc. as the material of the outer wall of the vacuum cavity, and this embodiment uses copper. Generally, a condensing agent absorbs or releases heat by using a phase change (change from a solid state to a liquid state or a gaseous state, conversion between a gaseous state and a liquid state, etc.), and belongs to a physical change. Not a chemical reaction. For example, air conditioners operate by using freon to emit heat when it is compressed from a gaseous state to a liquid state (condensation), and to absorb heat when it changes from a liquid state to a gaseous state (evaporation).

In specific implementation, the active rapid heat dissipation device of the thermal cycler based on the thermoelectric refrigeration piece also comprises a temperature controller; the temperature controller is connected with the temperature sensor of the heat dissipation VC temperature equalizing plate 210, the hot block thermoelectric refrigerating sheet 120 and the heat dissipation thermoelectric refrigerating sheet 220.

wherein the memory stores instructions executable by the at least one processor to enable the at least one processor to perform the above-described method for active rapid thermal dissipation of a thermal cycler based on thermoelectric cooling fins.

The invention also discloses a computer readable storage medium, wherein a computer program is stored, and when the computer program is executed by a processor, the active rapid heat dissipation method of the thermal cycler based on the thermoelectric refrigerating sheet is realized.

The specific logic algorithm control software adopts cascade PID control to cooperatively drive and control the working current and the output heat of the heat dissipation thermoelectric refrigerating sheet 220 and the thermal block thermoelectric refrigerating sheet 120, so that the temperature difference between the cold end surface and the hot end surface of the thermal block thermoelectric refrigerating sheet is kept within the range of 2-10 ℃, and the thermal block thermoelectric refrigerating sheet is ensured to be in the optimal working state.

When the PCR thermal cycle execution module heats the thermal block VC temperature-equalizing plate 110, the temperature control module of the temperature control software with specific logic algorithm actively starts the heat-dissipating thermoelectric cooling fins to heat the thermal block VC temperature-equalizing plate synchronously, and maintains the temperature difference Δ T between the upper and lower surfaces of the thermal block thermoelectric cooling fins 120 in a small range, so that the thermal block thermoelectric cooling fins keep a large heating capacity in the whole heating process, and the thermal block VC temperature-equalizing plate 110 heats quickly. Meanwhile, the temperature between the heat interfaces of the heat dissipation thermoelectric refrigeration piece and the heat pipe radiator is reduced, and the temperature compensation is carried out through the heat pipe radiator.

Before the PCR thermal cycle execution module cools the VC temperature-equalizing plate 110 of the PCR thermal block, the temperature control module of the temperature control software with specific logic algorithm actively starts the heat dissipation thermoelectric cooling plate 220 to cool the heat dissipation VC temperature-equalizing plate 210 in advance. At this time, the thermal block thermoelectric cooling plate 120 is still in a heating constant temperature state, and the heat dissipation VC temperature equalizing plate 210 in thermal contact with the lower end face of the thermal block thermoelectric cooling plate 120 is actively cooled in advance, so that the thermal block thermoelectric cooling plate 120 instantly reaches a high-efficiency cooling state with a low temperature when being converted into a cooling state, and the low-efficiency cooling of the thermal block thermoelectric cooling plate 120 at a high temperature is avoided, which results in a low cooling rate of the PCR tube PCR thermal block VC temperature equalizing plate 110. Meanwhile, the temperature between the thermal interfaces of the heat dissipation thermoelectric refrigerating fins and the heat pipe radiator is increased, and the heat is quickly dissipated through the heat pipe radiator.

The temperature control software with the specific logic algorithm sets at least one group of temperature control PID value and switch control value aiming at each variable temperature node of PCR nucleic acid amplification thermal cycle and stores the set values in the memory of the temperature controller.

The temperature control software of the specific logic algorithm controls the overshoot temperature of the thermal block thermoelectric refrigerating sheet to be 1-5 ℃ and the overshoot time to be 1-3 seconds at each variable temperature node of the PCR nucleic acid amplification thermal cycle.

The temperature control software with the specific logic algorithm adopts cascade PID control to drive and control the cooling thermoelectric refrigerating piece to be cooled to a temperature range which is 20-30 ℃ lower than the annealing temperature in advance at a temperature change node of the PCR nucleic acid amplification thermal cycle from the denaturation temperature to the annealing temperature.

As shown in fig. 1, the active rapid heat dissipation device includes at least one heat dissipation thermoelectric cooling fin. The heat dissipation thermoelectric refrigerating chip is used as a cold and heat source of the active rapid heat dissipation device and is driven and controlled by the specific logic algorithm control software through the temperature controller; the heat dissipation thermoelectric refrigerating piece can be a single piece or a plurality of series-parallel combination, and the power of the heat dissipation thermoelectric refrigerating piece is 1.5 to 3 times of that of the thermal block thermoelectric refrigerating piece.

In particular, the temperature controller includes a temperature control plate and a temperature sensor. The temperature controller comprises at least one temperature control board with control software of a specific logic algorithm and at least one temperature sensor. The specific logic algorithm (FIG. 2) includes, but is not limited to, a cascade PID control algorithm; a fuzzy PID control algorithm or an intelligent PID control algorithm may also be selected. The temperature sensor is used for monitoring the real-time temperature value of the heat dissipation VC temperature equalizing plate.

Referring to fig. 3, 4 and 5, an active fast heat dissipation device of a PCR thermal cycle execution module for 8 PCR tubes is shown in a first embodiment.

In this embodiment, the target heat dissipation object is a PCR thermal cycle module with 8 PCR tubes, which belongs to a flat plate fixed thermal cycle device, and performs PCR thermal cycle amplification reaction on PCR reagents in each PCR tube through 8 PCR tube holes of the PCR thermal block VC temperature-uniforming plate 110.

The PCR thermal cycle execution module of the embodiment comprises a PCR thermal block VC temperature-equalizing plate 110 and a thermal block thermoelectric cooling plate 120; 2 rows of 8 PCR tube heat blocks of 0.2mL which are connected with a VC temperature-uniforming plate into a whole are adopted, one heat block thermoelectric refrigerating sheet is adopted as a cold and heat source, and the size of the end surface of the thermoelectric refrigerating sheet executed by heat circulation is 40mm multiplied by 30mm in width.

Furthermore, 3 rows of 12 PCR tube thermal blocks of 0.2mL can be used with the end face size, and 4 rows of 16 PCR tube thermal blocks of 0.2mL can be used with the end face size of a thermoelectric cooling plate with the length of 40mm multiplied by the width of 40 mm.

The active fast heat dissipation device of this embodiment includes a heat dissipation VC temperature equalizing plate 210, a heat dissipation thermoelectric cooling plate 220, a liquid metal medium 230, a heat pipe heat dissipation assembly 240, and a heat dissipation fan 250.

The PCR thermal cycle execution module, the active rapid heat dissipation device and the temperature controller form a PCR thermal cycle module.

Liquid metal media 230 is coated or placed between each heat transfer interface separately, including: the thickness of the liquid metal medium 230 is between 0.1mm and 0.5mm between the PCR temperature execution thermoelectric refrigeration sheet 120 and the heat dissipation VC temperature-equalizing plate 210, between the heat dissipation VC temperature-equalizing plate 210 and the heat dissipation thermoelectric refrigeration sheet 220, and between each heat transfer interface of the heat dissipation thermoelectric refrigeration sheet 220 and the heat pipe heat dissipation assembly 240.

The liquid metal medium 230 includes, but is not limited to, a liquid metal heat conducting agent, a liquid metal alloy, a liquid metal heat conducting paste, a liquid metal heat conducting glue, or a phase-change liquid metal alloy sheet, and any one of them may be selected as the liquid metal medium in the specific implementation.

The heat dissipation VC temperature equalization plate 210 is usually made of a metal material with high thermal conductivity, and usually includes metal materials such as gold, silver, copper, and aluminum as the outer wall material of the vacuum cavity, in which copper is used in this embodiment.

The heat dissipation thermoelectric cooling plate 220 may be a single one or a plurality of series or parallel combinations, in this embodiment, 1 thermoelectric cooling plate of 40mm × 40mm is adopted, and the power of the thermoelectric cooling plate is 1.5-2 times of the power of the thermoelectric cooling plate executed at the temperature.

The heat pipe cooling assembly 240 and the cooling fan 250, in this embodiment, the heat pipe cooling assembly 240 and the cooling thermoelectric cooling fins 220 are used for heat conduction, and the liquid metal medium 230 is used for rapid heat conduction between the heat conduction interfaces.

The heat dissipation fan 250 is installed at the heat dissipation fins of the heat pipe heat dissipation assembly 240, cools or heats the heat dissipation fins of the heat pipe heat dissipation assembly 240 through air circulation, and finally cools or heats the heat pipe heat dissipation assembly 240, so as to ensure that the heat dissipation thermoelectric cooling fins 220 are in the optimal working state.

When the PCR temperature execution unit 100 heats the PCR tube heat block temperature equalizing plate 110, the temperature control unit actively starts the heat dissipation thermoelectric cooling fins 220 to synchronously heat the heat dissipation temperature equalizing plate 210, and maintains the temperature difference Δ T between the upper and lower surfaces of the PCR temperature execution thermoelectric cooling fins 120 in a small range, so that the PCR heat block thermoelectric cooling fins 120 keep a large heating capacity in the whole heating process, and the PCR tube heat block temperature equalizing plate 110 is rapidly heated. Meanwhile, the temperature between the thermal interfaces of the heat-dissipating thermoelectric cooling fins 220 and the heat pipe radiator 240 is reduced, and temperature compensation is performed through the heat pipe heat-dissipating component.

Before the PCR temperature execution unit 100 cools the PCR tube heat block temperature equalizing plate 110, the temperature control unit actively starts the heat dissipation thermoelectric refrigeration sheet 220 to cool the heat dissipation temperature equalizing plate 210 in advance, and at this time, the temperature execution thermoelectric refrigeration sheet 120 is still in a heating constant temperature state, and actively cools the heat dissipation VC temperature equalizing plate 210 in thermal contact with the lower end surface of the temperature execution thermoelectric refrigeration sheet 120 in advance, so that when the temperature execution refrigeration sheet 120 is converted into a refrigeration state, a high-efficiency refrigeration state with a low temperature is instantly reached, and the problem that the PCR tube heat block temperature equalizing plate 110 has a low cooling rate due to low-efficiency refrigeration of the PCR heat cycle temperature execution refrigeration sheet 120 at a high temperature is avoided. Meanwhile, the temperature between the thermal interfaces of the heat dissipation thermoelectric cooling fins 220 and the heat pipe radiator 240 rises, and the heat is quickly dissipated through the heat pipe heat dissipation assembly.

Referring to fig. 6, 7 and 8, a second embodiment of an active fast heat dissipation device for 3 sets of 8 PCR tube gradient nucleic acid amplification PCR temperature execution units is shown.

In this embodiment, a gradient PCR tube thermal block temperature equalizing plate is composed of 3 identical PCR tube thermal block temperature equalizing plates 110, and a gradient temperature executing unit is composed of 3 paths of temperature executing thermoelectric cooling fins 120 which are independently controlled. The temperature-executing thermoelectric cooling fins 120 of the present embodiment adopt 3 thermoelectric cooling fins 40mm × 10mm, and can generate different temperature gradients through 3 independent temperature control units, and respectively provide cold and heat sources for a group of 2 rows of 8 0.2mL PCR tube heat blocks integrally connected with the VC vapor chamber, so as to meet the requirements of gradient PCR reaction; if the 3 independent temperature control units generate the same temperature, the requirement of PCR reaction of 24 PCR tubes can be realized.

In specific implementation, for example, the temperatures of 3 identical PCR tube/block/isothermal plates 110 can be controlled to 59 ℃, 60 ℃ and 61 ℃. By controlling the temperature of the same PCR tube heat block temperature equalization plate 110 to be different, tests at different temperatures can be performed on the same instrument at one time, so that test results have better contrast.

As shown in FIG. 9, the temperature of 6 identical PCR tube thermal block isothermal plates 110 was controlled from low to high on 6 different gradients, thereby achieving the purpose of performing 6 sets of experiments simultaneously. As shown in fig. 9, the temperatures of the 1 st to 6 th channels are respectively controlled as follows: 52.2 ℃, 53.0 ℃, 54.0 ℃, 55.0 ℃, 56.0 ℃ and 57.0 ℃ and the temperature is increased in turn according to the preset control requirement. Therefore, the conditions of the same test at different temperatures can be met, and workers can easily perform comparative analysis at various temperatures, so that the test effect is improved.

Liquid metal media 230 is coated or placed between each heat transfer interface separately, including: the thickness of the liquid metal medium 230 is between 0.1mm and 0.5mm between the PCR temperature performing thermoelectric cooling plate 120 and the heat dissipation VC temperature equalizing plate 210, between the heat dissipation VC temperature equalizing plate 210 and the heat dissipation thermoelectric cooling plate 220, and between the heat transfer interfaces of the heat dissipation thermoelectric cooling plate 220 and the heat pipe heat dissipation assembly 240.

The liquid metal medium 230 includes, but is not limited to, a liquid metal heat conducting agent, a liquid metal heat conducting paste, and a phase-change liquid metal sheet, and the liquid metal medium adopted in the embodiment has a phase-change temperature of less than 30 ℃, a suitable viscosity, and good wettability with an interface material, and can effectively prevent the liquid metal from overflowing.

The heat dissipation VC temperature equalization plate 210 is usually made of a metal material with high thermal conductivity, and usually includes metal materials such as gold, silver, copper, aluminum, etc. as the outer wall material of the vacuum cavity, in this embodiment, copper is used as the outer wall material of the vacuum cavity of the heat dissipation VC temperature equalization plate 210, and the surface of the heat dissipation VC temperature equalization plate 210 can completely contain the 3 temperature execution thermoelectric cooling fins 120 of the gradient PCR, and can actively and quickly dissipate heat for the 3 temperature execution thermoelectric cooling fins 120.

The heat dissipation thermoelectric cooling plate 220 of the present embodiment is composed of 2 thermoelectric cooling plates of 40mm × 30mm connected in series or in parallel, and the total power of the thermoelectric cooling plate is 1.5-3 times of the total power of the thermoelectric cooling plate executed at 3 temperatures.

The heat pipe cooling assembly 240 and the cooling fan 250, in this example, the U-shaped heat pipe cooling assembly 240 is used for heat conduction of 2 thermoelectric cooling fins of 40mm × 30mm, and the liquid metal medium 230 is used for rapid heat conduction between the heat conduction interfaces.

The heat dissipation fan 250 is installed at the fin of the U-shaped heat pipe heat dissipation assembly 240, exhausts air downward according to the installation space position, cools or heats the fin of the heat pipe heat dissipation assembly 240 through air circulation, and finally cools or heats the heat pipe heat dissipation assembly 240, so as to ensure that the heat dissipation thermoelectric refrigerating fins are in the optimal working state.

When the PCR temperature execution unit 100 heats the PCR tube hot block temperature equalizing plate 110, the temperature control unit actively starts the heat dissipation thermoelectric cooling fin 220 to synchronously heat the heat dissipation VC temperature equalizing plate 210, and maintains the temperature difference Δ T between the upper and lower surfaces of the PCR temperature execution thermoelectric cooling fin 120 in a small range, so that the PCR hot block thermoelectric cooling fin 120 keeps a large heating amount in the whole heating process, and the PCR tube hot block temperature equalizing plate 110 rapidly heats. Meanwhile, the temperature between the thermal interfaces of the heat-dissipating thermoelectric cooling fins 220 and the heat pipe radiator 240 is reduced, and temperature compensation is performed through the heat pipe heat-dissipating component.

Before the PCR temperature execution unit 100 cools the PCR tube heat block temperature equalizing plate 110, the temperature control unit actively starts the heat dissipation thermoelectric cooling fin 220 to cool the heat dissipation temperature equalizing plate 210 in advance, at this time, the temperature execution thermoelectric cooling fin 120 is still in a heating constant temperature state, and actively cools the heat dissipation VC temperature equalizing plate 210 in thermal contact with the lower end face of the temperature execution thermoelectric cooling fin 120 in advance, so that the temperature execution cooling fin 120 instantly reaches a high-efficiency cooling state with a low temperature when being converted into a cooling state, thereby preventing the PCR heat cycle temperature execution cooling fin 120 from performing low-efficiency cooling at a high temperature, and causing the cooling rate of the PCR tube heat block temperature equalizing plate 110 to be low. Meanwhile, the temperature between the thermal interfaces of the heat dissipation thermoelectric cooling fins 220 and the heat pipe radiator 240 rises, and the heat is quickly dissipated through the heat pipe heat dissipation assembly.

Referring to fig. 10, 11 and 12, a third embodiment of an active fast heat dissipation module for fixing a temperature execution unit of a PCR chamber micro-fluidic chip is shown.

In this embodiment, the PCR temperature execution unit is composed of 1 fixed PCR cavity microfluidic chip thermal block VC temperature-equalizing plate 110 and a temperature execution thermoelectric cooling plate 120.

The VC temperature equalization plate 110 for fixing the PCR cavity microfluidic chip heat block is a flat VC temperature equalization plate without a PCR tube heat block.

The active fast heat dissipation unit 200, the heat dissipation VC temperature-uniforming plate 210 thereof, the heat dissipation thermoelectric cooling fins 220, the liquid metal medium 230, the heat pipe heat dissipation assembly 240, and the heat dissipation fan 250.

The PCR temperature execution unit 100, the active fast heat dissipation unit 200 and the temperature control unit 300 constitute a PCR thermal cycle module.

Liquid metal working fluid 230 is coated or placed between each heat transfer interface separately, including: the PCR temperature is performed between the thermoelectric cooling plate 120 and the heat dissipation VC temperature equalizing plate 210, between the heat dissipation VC temperature equalizing plate 210 and the heat dissipation thermoelectric cooling plate 220, and between the heat dissipation thermoelectric cooling plate 220 and each heat transfer interface of the heat pipe heat dissipation assembly 240.

The liquid metal medium 230 includes, but is not limited to, a liquid metal heat conducting agent, a liquid metal heat conducting paste, a phase-change liquid metal heat conducting paste, and a phase-change liquid metal sheet, and the liquid metal medium adopted in the embodiment has a phase-change temperature of less than 30 ℃, a proper viscosity, and good wettability with an interface material, and can effectively prevent the liquid metal from overflowing.

The heat dissipation and uniform temperature distribution plate 210 is usually made of a metal material with high thermal conductivity, and usually includes a metal material such as gold, silver, copper, aluminum, and the like.

The heat dissipating thermoelectric cooling fins 220 can be single or multiple in series or parallel combination,

the heat pipe cooling assembly 240 and the cooling fan 250 are used for heat conduction between the heat pipe cooling assembly 240 and the cooling thermoelectric cooling fins 220, the gallium-based liquid metal working medium 230 is used for rapid heat conduction between heat conduction interfaces, and the gallium-based liquid metal working medium 230 is sealed by heat-conducting silica gel.

The heat dissipation fan 250 is installed at the fins of the heat pipe heat dissipation assembly 240, and cools or heats the fins of the heat pipe heat dissipation assembly 240 through the air flow channel, and finally cools or heats the heat pipe heat dissipation assembly 240, so as to ensure that the heat dissipation thermoelectric cooling fins are in an optimal working state.

When the PCR temperature execution unit 100 heats up the PCR tube heat block temperature equalizing plate 123, the temperature control unit actively starts the heat dissipation thermoelectric cooling fins 220 to heat up the heat dissipation temperature equalizing plate 210 synchronously, and maintains the temperature difference T between the upper surface and the lower surface of the PCR temperature execution thermoelectric cooling fins 120 in a small range, so that the PCR heat block thermoelectric cooling fins 120 keep a large heating capacity in the whole heating process, and the PCR tube heat block temperature equalizing plate 110 heats up quickly. Meanwhile, the temperature between the thermal interfaces of the heat-dissipating thermoelectric cooling fins 220 and the heat sink 2 is reduced, and temperature compensation is performed by the heat pipe heat-dissipating component.

Before the PCR temperature execution unit 100 cools the PCR tube heat block temperature equalizing plate 110, the temperature control unit actively starts the heat dissipation thermoelectric cooling fin 220 to cool the heat dissipation temperature equalizing plate 210 in advance, at this time, the temperature execution thermoelectric cooling fin 120 is still in a heating state, and actively cools the heat dissipation temperature equalizing plate 210 in thermal contact with the lower end of the temperature execution thermoelectric cooling fin 120 in advance, so that the temperature execution cooling fin 120 instantly reaches a high-efficiency cooling state with lower temperature when being converted into a cooling state, and the problem that the PCR tube heat block temperature equalizing plate 110 is low in cooling rate due to low-efficiency cooling of the PCR heat circulation temperature execution cooling fin 120 at high temperature is avoided. Meanwhile, the temperature between the thermal interfaces of the heat-dissipating thermoelectric cooling fins 220 and the heat pipe radiator 240 rises, and heat is dissipated quickly through the heat pipe heat dissipation assembly.

In the embodiment, a sample machine of the fixed PCR cavity microfluidic chip nucleic acid amplification PCR instrument reaches the level of heating up by 12 ℃/s and cooling down by 10 ℃/s, and the heating-down rate is more than 3 times of that of a mainstream product in the prior art and more than 2 times of that of a high-end product.

The active quick heat dissipation device comprises at least one thermoelectric refrigeration piece used as an active heat dissipation cold and heat source; the active rapid heat dissipation device comprises at least one VC temperature equalization plate and a liquid metal medium arranged between every two thermal interfaces.

The temperature controller comprises a temperature controller adopting temperature control software (shown in figure 2) of a cascade PID control logic algorithm, and a heat cycle execution module and a thermoelectric refrigerating sheet in the active quick heat dissipation device are cooperatively driven and controlled. The temperature control module comprises at least one temperature sensor which respectively monitors the target temperature of the thermal cycle execution module and the target temperature of the active quick heat dissipation device.

The method can provide active rapid heat dissipation for at least one thermal cycle execution module at the same time. The method ensures that the thermal cycle execution module is in the optimal working state, improves the temperature change rate of temperature rise and temperature reduction in the thermal cycle process, and realizes the rapid heat transfer to the thermal cycle execution module, thereby shortening the total time of thermal cycle, and being particularly suitable for the temperature control of a PCR thermal cycler based on thermoelectric refrigeration sheets.

The present invention has the following features.

1) The method adopts at least one heat-dissipation thermoelectric refrigerating piece to actively dissipate heat of a thermal cycle execution thermoelectric refrigerating piece of the PCR nucleic acid amplification thermal cycler, and comprises the following steps of combining a plurality of thermal cycle execution thermoelectric refrigerating pieces (such as: a single thermal cycle performing thermoelectric cooling fins in the first embodiment, and a plurality of thermal cycles performing thermoelectric cooling fins in the second embodiment);

2) At least one heat dissipation thermoelectric cooling plate is adopted to carry out the active heat dissipation of the thermoelectric cooling plate on the temperature thermal cycle of the PCR nucleic acid amplification thermal cycler, and the PCR nucleic acid amplification thermal cycler comprises different PCR sample devices (such as: a PCR tube thermal cycling (PCR) unit in examples 1 and 2, a reaction chamber microfluidic chip thermal cycling (PCR) unit in the third example);

3) By software of a specific logic algorithm in the temperature controller, including but not limited to a cascade PID control algorithm; the fuzzy PID control algorithm or the intelligent PID control algorithm can be selected to cooperate with the heat dissipation thermoelectric refrigeration piece and the thermal cycle to execute the working temperature and the temperature change rate of the thermoelectric refrigeration piece, and the method comprises the following steps:

(3-1) specific logic algorithm software in the temperature controller drives the heat dissipation thermoelectric refrigerating piece and the thermal cycle execution refrigerating piece to synchronously change the temperature, so that the temperature difference between the cold and hot end surfaces of the hot block thermoelectric refrigerating piece is reduced, the hot block thermoelectric refrigerating piece is ensured to be in the optimal working state in the whole temperature changing stage, and the higher temperature changing speed is achieved.

(3-2) setting at least one group of temperature control PID values by specific logic algorithm software in the temperature controller aiming at each variable temperature node of PCR nucleic acid amplification thermal cycle, and ensuring that the thermal block thermoelectric refrigerating sheet and the heat dissipation thermoelectric refrigerating sheet reach the optimal variable temperature rate at each variable temperature node;

(3-3) controlling the overshoot temperature and the overshoot time of the thermal block thermoelectric refrigerating chip at each temperature changing temperature node of the PCR nucleic acid amplification thermal cycle by specific logic algorithm software in the temperature controller, and shortening the temperature changing time of the PCR sample reagent.

4) The temperature execution unit and the heat dissipation execution unit both use liquid metal media with high heat conductivity coefficient as heat conduction materials, and the liquid metal media include but are not limited to liquid metal heat conduction agents, liquid metal alloys, liquid metal heat conduction pastes, liquid metal heat conduction adhesives or phase-change liquid metal alloy sheets.

5) The liquid metal medium is coated or placed between the heat transfer interfaces of the PCR hot block VC temperature equalizing plate and the temperature execution thermoelectric refrigerating sheet of the temperature execution unit, also coated or placed between the heat dissipation VC temperature equalizing plate and the heat dissipation thermoelectric refrigerating sheet of the heat dissipation execution unit, and the heat interfaces of the heat dissipation thermoelectric refrigerating sheet and the heat pipe radiator, and similarly, the liquid metal medium is coated or placed between the heat interfaces of the temperature execution thermoelectric refrigerating sheet of the temperature execution unit and the heat dissipation VC temperature equalizing plate of the heat dissipation execution unit.

6) Sealing measures must be taken around the liquid metal media to prevent liquid metal from escaping between the heat transfer interfaces, including but not limited to: silicone rubber, heat-conducting silicone rubber, silicone rubber foam, polyurethane foam and the like.

7) The phase transition temperature of the specially-made liquid metal medium heat conducting paste is less than 30 ℃, the viscosity is proper, the wettability with an interface material is good, and the liquid metal is prevented from overflowing.

8) The VC temperature equalization plate is used as a bottom plate of a PCR heat block of a temperature execution unit, the diffusion heat resistance is reduced, and the effects of rapid heat conduction and temperature equalization are achieved.

9) The heat dissipation temperature equalization plate uses a VC temperature equalization plate as a heat dissipation execution unit, and a steam cavity of the heat dissipation VC temperature equalization plate is filled with refrigerant liquid including but not limited to water (boiling point 100 ℃), ethanol (boiling point 78.3 ℃), methanol (boiling point 64.8 ℃), acetone (boiling point 56.53 ℃), butane or other refrigerant liquid.

10 A heat pipe is adopted as a final radiator component, a vapor cavity of the heat pipe is filled with liquid including but not limited to water (with a boiling point of 100 ℃), ethanol (with a boiling point of 78.3 ℃), methanol (with a boiling point of 64.8 ℃), acetone (with a boiling point of 56.53 ℃), butane or other refrigerants, the section of the heat pipe comprises a circular ring or a rectangle, and the heat pipe can be matched with fins for heat dissipation and can also be matched with other metal plates for heat dissipation.

The temperature control software with specific logic algorithm in the invention sets at least one group of temperature control PID value and switch control value for each variable temperature node of PCR nucleic acid amplification thermal cycle, and stores the set values in the memory of the temperature controller.

The temperature control software with the specific logic algorithm adopts cascade PID control to drive and control the heat dissipation refrigerating sheet at a temperature change node of the PCR nucleic acid amplification thermal cycle from the denaturation temperature to the annealing temperature, and the temperature is lowered to a temperature range 20-30 ℃ lower than the annealing temperature in advance.

The invention mainly aims to provide an active rapid heat dissipation device and method based on thermoelectric cooling fins, which adopt new materials such as liquid metal, steam cavity temperature-equalizing plates, heat pipe radiators and the like, and new technologies such as optimization of a hot block structure, cascade PID temperature control software and the like, aim to solve the key technical problem of low temperature rise and fall rate of thermal cycle of the existing PCR nucleic acid amplification thermal cycler, and provide a rapid temperature rise and fall technical scheme for life science instruments and medical instruments.

It will be evident to those skilled in the art that the invention is not limited to the details of the foregoing illustrative embodiments, and that the present invention may be embodied in other specific forms without departing from the spirit or essential attributes thereof. The present embodiments are therefore to be considered in all respects as illustrative and not restrictive, the scope of the invention being indicated by the appended claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein. Any reference sign in a claim should not be construed as limiting the claim concerned.

Furthermore, it should be understood that although the present specification describes embodiments, not every embodiment includes only a single embodiment, and such description is for clarity purposes only, and it is to be understood that all embodiments may be combined as appropriate by one of ordinary skill in the art to form other embodiments as will be apparent to those of skill in the art from the description herein.

Claims

1. The active rapid heat dissipation method of the thermal cycler based on the thermoelectric refrigeration piece is characterized in that the method is used for actively dissipating heat of a thermal block thermoelectric refrigeration piece (120) of the thermal cycler;

step 1: arranging an active quick heat dissipation device for actively dissipating heat of the hot block thermoelectric refrigeration piece (120) on the hot block thermoelectric refrigeration piece (120), so that one side of a heat dissipation VC temperature equalizing plate (210) of the active quick heat dissipation device is attached to the hot block thermoelectric refrigeration piece (120);

step 2: at least one heat dissipation thermoelectric refrigerating sheet (220) is attached to the other side of the heat dissipation VC temperature-equalizing plate (210);

and step 3: the heat dissipation VC temperature equalizing plate (210) is heated or cooled through the heat dissipation thermoelectric refrigerating piece (220), so that the heat dissipation VC temperature equalizing plate (210) can heat or cool the hot block thermoelectric refrigerating piece (120), the temperature difference delta T between the upper surface and the lower surface of the hot block thermoelectric refrigerating piece (120) is kept in a preset value range all the time, and the hot block thermoelectric refrigerating piece (120) is ensured to be in an optimal working state;

the temperature controller acquires the actual temperature T0 of the heat block VC temperature-uniforming plate (110) and the actual temperature T1 of the heat dissipation VC temperature-uniforming plate through temperature sensors respectively arranged on the heat block VC temperature-uniforming plate (110) and the heat dissipation VC temperature-uniforming plate (210) of the PCR thermal cycle, and controls the heat output of the heat block thermoelectric cooling plate (120) and the heat dissipation thermoelectric cooling plate (220) through a temperature control program with a specific logic algorithm built in the temperature controller;

the PID control cycle of the thermal block VC temperature-equalizing plate of the PCR thermal cycle is a main control cycle, the temperature T0 of the thermal block VC temperature-equalizing plate (110) is a main object, and a cascade PID control main control cycle loop is formed by the thermal block VC temperature-equalizing plate temperature T0 sensor and the thermal block VC temperature-equalizing plate temperature T0 sensor; the heat dissipation PID control cycle is a secondary control cycle, the heat dissipation temperature T1 is a secondary object, and a secondary loop of cascade PID control is formed by the heat dissipation temperature T1 and the sensor.

2. The method as claimed in claim 1, wherein the thermal block thermoelectric cooling plate (120) and the active fast heat sink are connected to a temperature controller;

the temperature controller is used for controlling the thermal block thermoelectric refrigerating sheet (120) to enable the thermal block thermoelectric refrigerating sheet (120) to be heated or cooled;

the temperature controller is used for controlling the active quick heat dissipation device, so that the heat dissipation thermoelectric refrigerating sheet (220) of the active quick heat dissipation device is heated or cooled.

3. The active rapid thermal dissipation method for a thermal cycler based on thermoelectric cooling fins as claimed in claim 2, wherein a temperature control program is embedded in the temperature controller, and the temperature control program is used for executing a temperature control algorithm.

4. The active rapid thermal dissipation method of a thermal cycler based on thermoelectric cooling fins as recited in claim 3 wherein said temperature control algorithm comprises a cascade PID control algorithm.

5. The active rapid heat dissipation method for thermal cycler based on thermoelectric cooling fins as claimed in claim 3, wherein in the temperature control algorithm, when the thermal block thermoelectric cooling fins (120) need to cool the thermal block VC temperature equalizing plate (110), the heat dissipation VC temperature equalizing plate (210) is actively cooled in advance through the heat dissipation thermoelectric cooling fins (220).

6. The active rapid thermal dissipation method for thermal cycler based on thermoelectric cooling fins as claimed in claim 3, wherein in the temperature control algorithm, when the thermal block thermoelectric cooling fins (120) need to heat up the thermal block VC temperature equalizing plate (110), the temperature difference Δ T between the upper and lower surfaces of the thermal block thermoelectric cooling fins is within a predetermined value by controlling the heat dissipation VC temperature equalizing plate (210) of the active rapid thermal dissipation device and the thermal block VC temperature equalizing plate (110) to heat up synchronously.

7. The active rapid heat dissipation method for the thermal cycler based on thermoelectric cooling fins as claimed in claim 3, wherein at least one set of temperature control PID values is set for each variable temperature node of the PCR thermal cycle in the temperature control algorithm.

8. The active quick heat dissipation device of the thermal cycler based on the thermoelectric refrigeration piece is characterized in that the active quick heat dissipation device is arranged on a thermal block thermoelectric refrigeration piece (120) serving as a heat-dissipated object and used for enabling the temperature difference delta T between the upper surface and the lower surface of the thermal block thermoelectric refrigeration piece (120) to be kept within a preset value range all the time;

the active rapid heat dissipation device comprises at least one heat dissipation VC temperature-equalizing plate (210), at least one heat dissipation thermoelectric refrigerating sheet (220), a liquid metal medium (230), a conductive heat radiator and a convective heat radiator;

the temperature controller collects the actual temperature T0 of the heat block VC temperature-equalizing plate (110) and the actual temperature T1 of the heat dissipation VC temperature-equalizing plate through temperature sensors respectively arranged on the heat block VC temperature-equalizing plate (110) and the heat dissipation VC temperature-equalizing plate (210) of PCR thermal cycle, and controls the heat output of the heat block thermoelectric cooling piece (120) and the heat dissipation thermoelectric cooling piece (220) through a temperature control program with a specific logic algorithm built in the temperature controller;

the PID control cycle of the thermal block VC temperature-equalizing plate of the PCR thermal cycle is a main control cycle, the temperature T0 of the thermal block VC temperature-equalizing plate (110) is a main object, and a cascade PID control main control cycle loop is formed by the thermal block VC temperature-equalizing plate temperature T0 sensor and the PCR thermal block VC temperature-equalizing plate temperature T0 sensor; the heat dissipation PID control cycle is a secondary control cycle, the heat dissipation temperature T1 is a secondary object, and a secondary loop of cascade PID control is formed by the heat dissipation temperature T1 and the sensor.

9. The active rapid thermal cycler heat sink based on thermoelectric cooling fins as claimed in claim 8, wherein the heat sink VC temperature equalization plate (210) exchanges heat with the thermoelectric cooling fins (120), and the heat sink VC temperature equalization plate (210) conducts rapid heat with the thermoelectric cooling fins (120) through the liquid metal medium (230);

the heat dissipation VC temperature equalizing plate (210) and the heat dissipation thermoelectric refrigerating sheet (220) are subjected to heat exchange, and the heat dissipation VC temperature equalizing plate (210) and the heat dissipation thermoelectric refrigerating sheet (220) are subjected to rapid heat conduction through the liquid metal medium (230);

a liquid metal medium (230) is arranged between the heat dissipation thermoelectric refrigeration piece (220) and the conduction type radiator, and rapid heat conduction is carried out between the heat dissipation thermoelectric refrigeration piece (220) and the conduction type radiator through the liquid metal medium (230).

10. The active rapid thermal dissipation device of thermal cycler based on thermoelectric cooling fins as recited in claim 9, wherein the liquid metal medium (230) comprises a liquid metal heat conducting agent, a liquid metal alloy, a liquid metal heat conducting paste, a liquid metal heat conducting glue, or a phase-change liquid metal alloy fin.

11. The active rapid thermal dissipating device of a thermal cycler based on thermoelectric cooling fins as claimed in claim 8, wherein the coolant sealed inside the heat dissipating VC temperature equalization plate (210) comprises water, ethanol, methanol, acetone or butane.

12. The active rapid thermal dissipation device of claim 8, further comprising a temperature controller; the temperature controller is connected with a temperature sensor of the heat dissipation VC temperature equalizing plate (210), the hot block thermoelectric refrigerating sheet (120) and the heat dissipation thermoelectric refrigerating sheet (220).

13. An electronic device, comprising: at least one processor and a memory communicatively coupled to the at least one processor;

wherein the memory stores instructions executable by the at least one processor to enable the at least one processor to perform a method of thermal cycler active fast heat dissipation based on thermoelectric cooling fins as recited in any of claims 1 to 7.

14. A computer-readable storage medium, having stored thereon a computer program which, when executed by a processor, implements the method for active rapid thermal dissipation of a thermal cycler based on thermoelectric cooling fins of any of claims 1 to 7.