WO2021179442A1 - 热循环装置及pcr仪 - Google Patents

热循环装置及pcr仪 Download PDF

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Publication number
WO2021179442A1
WO2021179442A1 PCT/CN2020/092543 CN2020092543W WO2021179442A1 WO 2021179442 A1 WO2021179442 A1 WO 2021179442A1 CN 2020092543 W CN2020092543 W CN 2020092543W WO 2021179442 A1 WO2021179442 A1 WO 2021179442A1
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module
sample
heating
auxiliary heating
sample module
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PCT/CN2020/092543
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English (en)
French (fr)
Inventor
曹进涛
李冬
贺贤汉
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杭州博日科技有限公司
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Publication of WO2021179442A1 publication Critical patent/WO2021179442A1/zh

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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

Definitions

  • the invention relates to the technical field of biological detection, in particular to a thermal cycling device and a PCR machine.
  • PCR Polymerase Chain Reaction
  • cell-free molecular cloning or in vitro primer-directed enzymatic amplification of specific DNA sequences is a method of enzymatically synthesizing specific DNA fragments in vitro.
  • a few steps of reaction such as low-temperature annealing and temperature-appropriate extension form a cycle, which is carried out in cycles, so that the target DNA can be rapidly amplified.
  • PCR gene amplification instrument has the characteristics of strong specificity, high sensitivity, simple operation, and time saving.
  • the purpose of the present invention is to provide a thermal cycler and a PCR machine to alleviate the technical problem of uneven temperature of sample holes in different regions of the sample module.
  • the thermal cycle device includes: a sample module, a heating and cooling module, a heat dissipation module, an auxiliary heating module, and a seal;
  • the heating and cooling module is arranged between the sample module and the heat dissipation module, the auxiliary heating module and the sealing element are arranged around the sample module, the auxiliary heating module, the sealing element and the The sample module constitutes a confined space;
  • the auxiliary heating module heats the air in the enclosed space, and the heated air heats the surroundings of the sample module.
  • the heating power of the auxiliary heating module around the sample module is different.
  • the surrounding area of the sample module includes an air inlet side, an air outlet side, and a non-air outlet side.
  • the heating power on the air inlet side is greater than the heating power on the air outlet side.
  • the heating power is greater than the heating power on the side without the tuyere.
  • the enclosed space forms at least one independent enclosed space around the sample module.
  • a heat equalization module which is arranged between the heating and cooling module and the heat dissipation module.
  • the screw is arranged in the middle of the sample module, passes through the sample module, the heating and cooling module, and the heat equalizing module, and is fixed on the heat dissipation module; the screw
  • the thermal conductivity is between 40-50W/mK.
  • sample module is divided into a plurality of sections, each section includes a plurality of sample holes, and the screw is arranged in the center of each section.
  • the auxiliary heating module includes an auxiliary heating film and an auxiliary heating plate, and the auxiliary heating film is arranged on the auxiliary heating plate.
  • the bottom surface of the sample module has a first flange, and the first flange, the sample module main body, the auxiliary heating module, and the sealing element constitute the enclosed space; or the sealing The member has a second flange, and the second flange, the sample module, the auxiliary heating module, and the sealing member constitute the enclosed space; or the sealing member has a bottom plate, the bottom plate, The sample module, the auxiliary heating module and the sealing member constitute the enclosed space.
  • the PCR instrument provided by the present invention includes the thermal cycling device as described above.
  • the thermal cycling device and PCR instrument include: a sample module, a heating and cooling module, a heat dissipation module, an auxiliary heating module and a sealing element; the heating and cooling module is arranged between the sample module and the heat dissipation module, and auxiliary heating is arranged around the sample module Module and seal, auxiliary heating module, seal and sample module constitute a closed space; the auxiliary heating module heats the air in the closed space, and the heated air heats the surroundings of the sample module, so that the sample hole at the edge of the sample module can be heated Heat it up. Therefore, the temperature of the sample hole at the edge of the sample module is increased by air heating, and this heating method can make the heating more uniform, thereby making the temperature of the middle sample hole and the edge sample hole of the sample module more uniform.
  • thermal cycler and PCR machine provided by the present invention also have the following beneficial effects:
  • the thermal cycler and PCR machine provided by the present invention also have good storage performance.
  • the enclosed air will not flow with the outside air after being heated, so as to prevent the outside air from affecting the temperature of the enclosed air, so that the thermal circulation device and
  • the thermal cycler has a good preservation function. Even if the inspector does not keep track of the monitoring, when the monitoring is completed, when the auxiliary heating module stops heating, the airtight air can maintain its temperature for a certain period of time because it is not affected by the outside air.
  • the samples can be preserved continuously without failure and denaturation.
  • the thermal cycler and PCR instrument provided by the present invention can also increase the life of the heating and cooling module.
  • the above-mentioned enclosed space composed of the auxiliary heating module, the sealing element and the sample module can also isolate the outside air and reduce the damage to the heating and cooling module caused by the condensate caused by the outside air. Because the heating and cooling module usually needs to use a circuit board for power supply Therefore, it is possible to prevent the short-circuit influence of the condensed water on the circuit board and the heating and cooling module, and to improve the service life of the heating and cooling module.
  • the auxiliary heating module around the sample module is specially designed for power, that is, the heating power of the auxiliary heating module around the sample module is set to be different Power so that when the temperature of the sample hole around the sample module is different, the temperature of the sample hole around the sample module is made more uniform through different heating powers, so that the temperature of the middle sample hole and the edge sample hole of the sample module is more uniform, The temperature of the sample holes in different areas of the sample module is further evened.
  • the sample module is surrounded by the air inlet side, the air outlet side, and the airless side.
  • the temperature of the sample hole on the air inlet side is lower than the temperature of the sample hole on the air outlet side
  • the temperature of the sample hole on the air outlet side is lower than the air outlet side.
  • the temperature of the sample hole on the tuyere side therefore, the heating power on the side of the air inlet is greater than the heating power on the side of the outlet, and the heating power on the side of the outlet is greater than the heating power on the side without the air outlet, thereby reducing the different sides of the edge
  • the temperature between the sample holes is not uniform. As a result, the temperature of the sample wells in multiple regions of the sample module is more uniform, and the overall gene amplification effect and detection performance accuracy and stability of the PCR instrument are improved.
  • a heat equalization module is arranged between the heating and cooling module and the heat dissipation module, so that the temperature between the sample holes in each area of the sample module is further uniform.
  • the temperature of the sample hole in the middle of the sample module is reduced by using a screw located in the middle of the sample module with a certain degree of heat dissipation, thereby making the sample module
  • the temperature of the middle sample hole and the edge sample hole are further uniform; and the sample module, the heating and cooling module and the soaking module are fixed on the radiator with screws, which can make the heating and cooling module and the sample module and the soaking module tightly spaced.
  • the bonding has a certain thermal conductivity, thereby reducing the temperature unevenness between the middle sample hole and the edge sample hole.
  • the screw can also make the heating and cooling module more uniform, so that in the high and low temperature operation of the sample module, the deformation of the heating and cooling module is small, and its life is further prolonged.
  • Figure 1 is a schematic cross-sectional view of a thermal cycler provided by an embodiment of the present invention
  • Figure 2 is a schematic diagram of a sample module provided by an embodiment of the present invention.
  • Figure 3 is a schematic cross-sectional view of another thermal cycler provided by an embodiment of the present invention.
  • FIG. 4 is a schematic front view of a thermal cycle device provided by an embodiment of the present invention.
  • Fig. 5 is a schematic diagram of a heat dissipation module provided by an embodiment of the present invention.
  • Icon 1-sample module; 2- heating and refrigeration module; 3- cooling module; 4- auxiliary heating module; 41- auxiliary heating plate; 42- auxiliary heating film; 5- seal; 6-closed space; 7- sample hole ;8-Heat soaking module; 9-air inlet side; 10-air outlet side; 11-no air outlet side; 12-screw; 13-decorative board; 14-layering; 15-circuit board; 16-quality reduction hole ; 17-section; 18-air inlet; 19-air outlet; 20-fan; 21-thermal interface material.
  • the phenomenon of inconsistent speed causes the temperature of the middle sample hole to be much higher than the temperature of the edge sample hole, resulting in uneven temperature of the sample hole in different areas of the sample module.
  • the thermal cycler and PCR instrument provided by the embodiments of the present invention increase the temperature of the sample hole at the edge of the sample module by air heating, and this heating method can make the heating more uniform, thereby making the intermediate sample of the sample module The temperature of the hole and the edge sample hole is more uniform.
  • thermal cycler and PCR instrument disclosed in the embodiment of the present invention are first introduced in detail.
  • Figure 1 shows a schematic diagram of a thermal cycler provided by an embodiment of the present invention.
  • the thermal cycle device includes: a sample module 1, a heating and cooling module 2, a heat dissipation module 3, an auxiliary heating module 4, and a sealing member 5; the heating and cooling module 2 is arranged in the sample module 1 and Between the heat dissipation modules 3, an auxiliary heating module 4 and a sealing member 5 are arranged around the sample module 1.
  • the auxiliary heating module 4, the sealing member 5 and the sample module 1 constitute a closed space 6; Heating, the heated air heats the surroundings of the sample module 1.
  • the sample module 1 includes a PCR orifice plate for carrying samples, and the PCR orifice plate is provided with a plurality of sample holes 7.
  • the number of sample wells 7 is not limited, such as 12, 24, 48, 96, 192, or 384, etc., and the arrangement of sample wells 7 is also not limited, and the usual sample wells 7 are arranged.
  • it may be an 8 ⁇ 12 array or a 12 ⁇ 8 array of 96 holes, or a 16 ⁇ 24 array of 384 holes, or an 8 ⁇ 6 array or a 16 ⁇ 3 array of 48 holes, and so on.
  • the sample module 1 may be divided into a plurality of sections, and each section includes a plurality of sample holes 7.
  • the sample module 1 includes a sample block section, which is divided into 6 sections 17, each section 17 includes a recess for forming the sample hole 7, forming There are 16 sample holes 7, a total of 96 sample holes 7, which are arranged in a rectangular shape, and the sample holes 7 are used to hold heat cycle samples.
  • a mass reduction hole 16 may be provided between the sample holes 7 on the sample block section, and the mass reduction hole 16 removes mass from the block, so as to reduce the thermal mass of the sample block section.
  • the heating and cooling module 2 may include heating and cooling fins to heat or cool the sample module 1; the heat dissipation module 3 may use a radiator to dissipate the sample module 1; the seal 5 may be made of rubber or other materials The gasket.
  • a heating and cooling module 2 may be provided on the bottom surface of the sample module 1, and a heat dissipation module 3 may be provided under the heating and cooling module 2.
  • the sample module 1 further includes a decorative board 13.
  • the sealing member 5 can be arranged under the decorative board 13.
  • the auxiliary heating module 4, the sealing member 5, and the sample module 1 form a closed space 6, and the air in the closed space 6 can directly interact with The sample module 1 contacts.
  • the heating and cooling module 2 also includes a circuit board 15 through which power is supplied to the heating and cooling fins.
  • the sample module 1 can also be fixed with the heating and cooling module 2 through the pressing bar 14.
  • the embodiment uses a heating auxiliary module to heat the air in the enclosed space 6 around the sample module 1, the heated air heats the sample hole at the edge of the sample module 1, and the temperature of the sample hole at the edge of the sample module 1 is obtained by air heating.
  • This heating method can make the heating more uniform, so that the temperature of the middle sample hole and the edge sample hole of the sample module 1 is more uniform.
  • the above-mentioned enclosed space 6 makes the enclosed air not flow with the outside air after being heated, and has a good thermal insulation effect, so that the thermal cycle device has a good preservation function; therefore, even if the inspector does not continue to track and monitor, such as the inspection process When the inspection personnel are out or off work, when the monitoring is completed, the heated air can keep the sample continuously without degeneration.
  • the enclosed space 6 can also isolate the outside air, reduce the condensed water brought by the outside air, and prevent the condensed water from damaging the heating and cooling module 2, for example, preventing the circuit board and the heating and cooling fins of the heating and cooling module 2 from causing a short circuit. The service life of the heating and cooling module 2 is improved.
  • the heating power of the auxiliary heating module 4 around the sample module 1 is different.
  • the temperature of the sample holes around the sample module 1 may be different.
  • the heating power can make the temperature of the sample hole around the sample module 1 more uniform.
  • the auxiliary heating module 4 may be arranged around the sample module 1. Since the heat dissipation module 3 performs heat dissipation and cooling for the sample module 1 through convection and heat exchange with the outside wind, as shown in Figures 4 and 5, the heat dissipation module 3 includes an air inlet 18 and an air outlet 19, correspondingly, the sample The module 1 includes an air inlet side 9, an air outlet side 10 and an airless side 11. The outside wind enters from the air inlet 18 of the heat dissipation module 3 and exits from the opposite air outlet 19. When the outside wind starts to enter the heat dissipation module 3, it can quickly cool down the air inlet side 9 of the sample module 1 and reach the heat dissipation module. 3.
  • the heating power around the sample module 1 is set as: the heating power on the side of the air inlet 9 is greater than the heating power on the side of the air outlet 10, and the heating power on the side of the air outlet 10 is greater than the heating power on the side without air outlet 11.
  • the heating power is set as: the heating power on the side of the air inlet 9 is greater than the heating power on the side of the air outlet 10, and the heating power on the side of the air outlet 10 is greater than the heating power on the side without air outlet 11.
  • the fan 20 in order to improve the heat dissipation efficiency of the heat dissipation module 3, the fan 20 can be placed on one side of the heat dissipation module 3 (the air inlet portion 18), but this will further cause the air inlet and outlet portions of the heat dissipation module 3
  • the temperature difference of 19 becomes larger, and the temperature difference between the air inlet side 9 and the air outlet side 10 of the sample module 1 is more obvious.
  • the current PCR machine superimposes the edge effect of the sample module 1 with the temperature difference of the above-mentioned different sides, which will cause the temperature distribution of the sample module 1 to be: temperature in the middle area> temperature on the side of the air outlet> temperature on the side of the air outlet> The temperature on the side of the air inlet.
  • an auxiliary heating module 4 is added around the sample module 1, so that the temperature of the middle sample hole and the edge sample hole of the sample module is more uniform.
  • the power of the four sides of the auxiliary heating module is designed to be different, so that the heating power on the side of the air inlet>the heating power on the side of the air outlet>the side without the air outlet
  • the heating power is used to compensate for the uneven temperature of the sample holes around the sample module 1. While making the temperature of the middle sample hole and the edge sample holes more uniform, the temperature of the sample holes around the sample module 1 is further evened out, which is better. The temperature uniformity.
  • the above-mentioned auxiliary heating module 4 includes an auxiliary heating film 42 and an auxiliary heating plate 41, and the auxiliary heating film 42 is disposed on the auxiliary heating plate 41.
  • the auxiliary heating plate 41 may specifically be an aluminum plate.
  • the auxiliary heating film 42 is arranged on the aluminum plate by glue or other methods.
  • the auxiliary heating film 42 heats the aluminum plate.
  • the heated aluminum plate heats the air in the enclosed space 6 because the air is airtight. , The use of air transfer to make the enclosed space 6 have a certain temperature.
  • the air can make the heat transfer more evenly in the enclosed space 6, and the enclosed air is directly in contact with the side of the sample module 1, the temperature of the surrounding environment of the sample module 1 is increased, so that the enclosed air can transfer the sample at the edge of the sample module 1.
  • the holes 7 are uniformly heated to reduce the temperature difference between the edge sample hole 7 and the middle sample hole 7 and improve the temperature uniformity of the sample module 1.
  • the above-mentioned auxiliary heating film may include a plurality of heating films with different heating powers, which are respectively arranged around the sample module, so that the heating power on the side of the air inlet>the heating power on the side of the air outlet>the heating power on the side without the air outlet.
  • auxiliary heating film In addition to the above-mentioned auxiliary heating film, multiple heating films with different heating powers can also be used.
  • One heating film can be used to compensate for the uneven temperature of the sample holes around the sample module 1 by setting the arrangement density of the heating wires to be different.
  • the arrangement density of the heating wires can be set as: arrangement density on the side of the air inlet> arrangement density on the side of the air outlet> arrangement density on the side of the air outlet.
  • auxiliary heating module 4 and sealing member 5 when a circle of auxiliary heating module 4 and sealing member 5 is arranged around sample module 1, so that auxiliary heating module 4, sealing member 5 and sample module 1 together form a closed space 6,
  • the enclosed space 6 can form at least one independent enclosed space around the sample module 1, that is, the enclosed space 6 can be a connected enclosed space, that is, an independent enclosed space; it can also be a side of the sample module 1.
  • the other three sides are connected closed spaces to form two independent closed spaces; or you can also set two sides as independent closed spaces, and the other two sides are connected closed spaces to form Three independent confined spaces; or as a preferred method, isolate the confined spaces on the four sides of the sample module 1 to form four independent confined spaces, so that the four independently confined confined spaces together form an auxiliary Heating space.
  • the air between the four independent enclosed spaces does not flow, and the auxiliary heating module 4 of different heating power heats the enclosed space on the corresponding side, which can make the sample module 1 different
  • the temperature of the sample hole on the side edge becomes uniform more quickly.
  • the enclosed space 6 forms an independent enclosed space, two independent enclosed spaces, or three independent enclosed spaces, although the air on different sides of the sample module 1 may flow between them, the air on different sides may flow.
  • the auxiliary heating modules 4 with different heating powers are closer to the sample module 1 on the side where they are located. After heating the air on the side where they are located, the sample module 1 on that side can be directly heated, so that the samples on different sides of the sample module 1 can be heated. The hole temperature becomes uniform.
  • the enclosed space 6 is composed of the sample module 1, the auxiliary heating module 4 and the sealing member 5, for example, the following construction methods (1), (2) or (3):
  • the bottom surface of the sample module 1 has a first flange portion facing the sealing member 5, and the first flange portion is closely attached to the sealing member 5 so that the first flange portion, the sample module body, and the auxiliary heating module 4 And the sealing member 5 can form a closed space 6.
  • the sealing member 5 has a second flange portion facing the sample module 1, and the second flange portion is closely attached to the sample module 1, so that the second flange portion, the sample module 1, the auxiliary heating module 4 and the sealing
  • the piece 5 can constitute a closed space 6.
  • the bottom plate under the sealing member 5, and the bottom plate is closely attached to the sealing member 5 and the sample module 1, so that the bottom plate, the sample module 1, the auxiliary heating module 4 and the sealing member 5 can form a closed space 6.
  • the aforementioned bottom plate can be used as a reinforcement or other functional components.
  • the bottom plate can also be the aforementioned circuit board 15, which is not limited here.
  • the above-mentioned configuration is not a limitation, as long as the sample module 1, the auxiliary heating module 4, and the sealing member 5 can form a closed space.
  • the thermal cycle device further includes a heat equalization module 8, and the equalization module 8 may be arranged between the heating and cooling module 2 and the heat dissipation module 3.
  • a heat equalization module 8 is provided on the bottom surface of the heating and cooling module 2, and the bottom surface of the equalization module 8 is provided on the heat dissipation module 3.
  • the soaking module 8 may adopt a soaking plate, and the soaking plate may be provided with an equalizing cavity structure, and the equalizing cavity structure includes a vacuum cavity.
  • the temperature uniformity of the heating and cooling module 2 can be ensured, and the dynamic temperature of the sample module 1 can be improved. Uniformity.
  • the thermal cycler device further includes a screw 12, which can be arranged in the middle of the sample module 1, and the screw 12 passes through the sample module 1, the heating and cooling module 2, and
  • the soaking module 8 is fixed on the heat dissipation module 3, and its thermal conductivity is between 40-50W/mK.
  • a plurality of holes for mounting screws 12 can be provided in the middle of the sample module 1.
  • the sample module 1 is usually divided into a plurality of sections 17, each section 17 includes a plurality of sample holes 7, and the screw 12 can be arranged in the center of each section 17, as shown in FIG. 2.
  • the screw 12 can be made of a material with high thermal conductivity and high heat dissipation performance, such as aluminum, etc., because its thermal conductivity is between 40-50 W/m.K, it has good thermal conductivity.
  • the screw 12 can reduce the temperature of the sample hole 7 in the middle of the sample module 1 where it is located, thereby further reducing the middle sample hole 7 and the edge sample hole 7 The temperature difference can improve the temperature uniformity of the sample module 1.
  • the screw 12 passes through the sample module 1, the heating and cooling module 2, the soaking module 8, and is finally fixed on the heat dissipation module 3, so that the above-mentioned multiple components can be better fixed.
  • the heating and cooling module 2 usually adopts heating and cooling fins. Because the heating and cooling fins are relatively long and are prone to bends, they do not fit well with the sample module 1 and the soaking module 8, which affects the thermal conductivity and makes the heating and cooling module 2. A higher power is required to heat up.
  • the screw 12 in the middle of the sample module 1 can make the heating and cooling module 2 and the sample module 1 and the soaking module 8 have a tight fit, so that the heat conduction effect is good, so that the heating and cooling module 2 can be heated and cooled.
  • the heat is transferred out faster, which can make the temperature of the sample module 1 more uniform, without the need to heat the refrigeration module 2 to have higher power.
  • the screw 12 can also make the heating and cooling module 2 more evenly stressed. During the high and low temperature operation of the sample module 1, the heating and cooling module 2 has a small deformation, thereby increasing the life of the heating and cooling module 2.
  • a thermal interface material 21 is provided between the heating and cooling module 2 and the sample module 1.
  • a thermal interface material 21 can be provided between the top surface of the heating and cooling module 2 and the bottom surface of the sample module 1.
  • the thermal interface material 21 is a thermally conductive material such as carbon film, thereby improving the gap between the heating and cooling module 2 and the sample module 1. Thermal conductivity between.
  • a thermal interface material can also be arranged between the heating and cooling module 2 and the soaking module 8 to improve the thermal conductivity between the heating and cooling module 2 and the soaking module 8.
  • the thermal cycle device includes: a sample module, a heating and cooling module, a heat dissipation module, an auxiliary heating module, and a seal; the heating and cooling module is arranged between the sample module and the heat dissipation module, and the auxiliary heating module is arranged around the sample module
  • the auxiliary heating module, the sealing element, and the sample module constitute a closed space; the auxiliary heating module heats the air in the closed space, and the heated air heats the surroundings of the sample module, so that the sample hole at the edge of the sample module can be heated. heating. Therefore, the temperature of the sample hole at the edge of the sample module is increased by air heating, and this heating method can make the heating more uniform, thereby making the temperature of the middle sample hole and the edge sample hole of the sample module more uniform.
  • thermal cycler provided by the embodiment of the present invention also has the following advantages:
  • the above-mentioned enclosed space composed of the auxiliary heating module, the sealing element and the sample module can also isolate the outside air and reduce the damage to the heating and cooling module caused by the condensate caused by the outside air. Because the heating and cooling module usually needs to use a circuit board for power supply Therefore, it is possible to prevent the short-circuit influence of the condensed water on the circuit board and the heating and cooling module, and to improve the service life of the heating and cooling module.
  • the auxiliary heating module around the sample module is specially designed for power, that is, the heating power of the auxiliary heating module around the sample module is set to be different Power so that when the temperature of the sample hole around the sample module is different, the temperature of the sample hole around the sample module is made more uniform through different heating powers, so that the temperature of the middle sample hole and the edge sample hole of the sample module is more uniform, The temperature of the sample holes in different areas of the sample module is further evened.
  • the heating power on the side of the air inlet is greater than the heating power on the side of the air outlet
  • the heating power on the side of the air outlet is greater than the heating power on the side without the air outlet, thereby reducing the difference between the sample holes on different sides of the edge.
  • the temperature is uneven. As a result, the temperature of the sample wells in multiple regions of the sample module is more uniform, and the overall gene amplification effect and detection performance accuracy and stability of the PCR instrument are improved.
  • a heat equalization module is arranged between the heating and cooling module and the heat dissipation module, so that the temperature between the sample holes in each area of the sample module is further uniform.
  • the embodiment of the present invention also provides a PCR machine, which includes the above thermal cycle device.
  • the thermal cycler of the above-mentioned embodiment is provided on the PCR machine, wherein the sample to be tested is placed in the sample hole on the sample module, usually a test tube containing the test solution.
  • the sample to be tested is required Heating and cooling are performed to meet the reaction temperature, and the thermal cycle device can ensure that the temperature of the sample hole is uniform, that is, the temperature of the sample to be tested is uniform, so as to obtain a uniform sample yield.
  • the PCR instrument of the embodiment of the present invention has the characteristics of uniform temperature, light weight, fast heating and cooling speed, and low power requirement, which greatly improves the overall gene amplification effect of the instrument and the accuracy and stability of detection performance.
  • the terms “installed”, “connected”, and “connected” should be understood in a broad sense, for example, they may be fixed connections or detachable connections. , Or integrally connected; it can be a mechanical connection or an electrical connection; it can be directly connected or indirectly connected through an intermediate medium, and it can be the internal communication between two components.
  • installed e.g., they may be fixed connections or detachable connections. , Or integrally connected; it can be a mechanical connection or an electrical connection; it can be directly connected or indirectly connected through an intermediate medium, and it can be the internal communication between two components.
  • the disclosed device may be implemented in other ways.
  • the device embodiments described above are merely illustrative.
  • the division of the units is only a logical function division, and there may be other divisions in actual implementation.
  • multiple units or components may be combined or It can be integrated into another system, or some features can be ignored or not implemented.
  • the displayed or discussed mutual coupling or direct coupling or communication connection may be through some communication interfaces, indirect coupling or communication connection of devices or units, and may be in electrical, mechanical or other forms.
  • the units described as separate components may or may not be physically separated, and the components displayed as units may or may not be physical units, that is, they may be located in one place, or they may be distributed on multiple network units. Some or all of the units may be selected according to actual needs to achieve the objectives of the solutions of the embodiments.
  • the functional units in the various embodiments of the present invention may be integrated into one processing unit, or each unit may exist alone physically, or two or more units may be integrated into one unit.
  • the function is implemented in the form of a software functional unit and sold or used as an independent product, it can be stored in a non-volatile computer readable storage medium executable by a processor.
  • the technical solution of the present invention essentially or the part that contributes to the prior art or the part of the technical solution can be embodied in the form of a software product, and the computer software product is stored in a storage medium, including Several instructions are used to make a computer device (which may be a personal computer, a server, or a network device, etc.) execute all or part of the steps of the methods described in the various embodiments of the present invention.

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Abstract

本发明提供的一种热循环装置及PCR仪，涉及生物检测技术领域，热循环装置包括：样品模块、加热制冷模块、散热模块、辅助加热模块及密封件；加热制冷模块设置于样品模块和散热模块之间，样品模块的周围设置辅助加热模块和密封件，辅助加热模块、密封件和样品模块构成密闭空间；辅助加热模块对密闭空间中的空气进行加热，加热后的空气对样品模块周围进行加热，从而可以对样品模块边缘的样品孔进行加热。本发明通过空气加热的方式使样品模块边缘的样品孔温度得到提升，并且这种加热方式可以使加热更均匀，从而使样品模块的中间样品孔与边缘样品孔的温度更加均匀。

Description

热循环装置及PCR仪
本申请要求于2020年03月10日提交中国专利局、申请号为202010161139.X、申请名称为“热循环装置及PCR仪”的中国专利申请的优先权，其全部内容通过引用结合在本申请中。
技术领域
本发明涉及生物检测技术领域，尤其是涉及一种热循环装置及PCR仪。
背景技术
聚合酶链式反应(Polymerase Chain Reaction，PCR)，又称无细胞分子克隆或特异性DNA序列体外引物定向酶促扩增技术，是体外酶促合成特异DNA片段的一种方法，由高温变性、低温退火及适温延伸等几步反应组成一个周期，循环进行，使目的DNA得以迅速扩增。PCR基因扩增仪具有特异性强、灵敏度高、操作简便、省时等特点，它不仅可用于基因分离、克隆和核酸序列分析等基础研究，还可用于疾病的诊断或任何有DNA，RNA的地方，因而在分子生物学、微生物学、医学及遗传学等多领域广泛应用和迅速发展。
在PCR热循环期间，需要保持热的均匀性，使整个一组不同的样品孔保持均匀的加热和冷却，得到均匀的样品产率，样品孔之间可以提供定量的产率均匀。然而，目前市场的PCR基因扩增仪，其样品模块机构均采用整体材料精加工或铸造而成，都存在模块机构的边缘效应，即存在中间样品孔与边缘样品孔之间的热均匀性差及升降温速度不一致的现象，使得中间样品孔温度高于边缘样品孔温度，导致样品模块的不同区域的样品孔温度不均匀。
发明内容
本发明的目的在于提供热循环装置及PCR仪，以缓解了样品模块的不同区域的样品孔温度不均匀的技术问题。
本发明提供的热循环装置，包括：样品模块、加热制冷模块、散热模块、辅助加热模块及密封件；
所述加热制冷模块设置于所述样品模块和所述散热模块之间，所述样品模块的周围设置所述辅助加热模块和所述密封件，所述辅助加热模块、所述密封 件和所述样品模块构成密闭空间；
所述辅助加热模块对所述密闭空间中的空气进行加热，加热后的空气对所述样品模块周围进行加热。
进一步的，所述辅助加热模块在所述样品模块周围的加热功率不同。
进一步的，所述样品模块周围包括进风口一侧、出风口一侧以及无风口侧，所述进风口一侧的加热功率大于所述出风口一侧的加热功率，所述出风口一侧的加热功率大于所述无风口侧的加热功率。
进一步的，所述密闭空间在所述样品模块的四周形成至少一个独立密闭空间。
进一步的，还包括均热模块，所述均热模块设置在所述加热制冷模块和所述散热模块之间。
进一步的，还包括螺钉，所述螺钉设置在所述样品模块的中间，并且穿过所述样品模块、所述加热制冷模块和所述均热模块，固定在所述散热模块上；所述螺钉的导热系数在40-50W/m.K之间。
进一步的，所述样品模块分为多个区段，每个所述区段包括多个样品孔，所述螺钉设置在每个所述区段的中央。
进一步的，所述辅助加热模块包括辅助加热膜和辅助加热板，所述辅助加热膜设置在所述辅助加热板上。
进一步的，所述样品模块的底面具有第一凸缘部，所述第一凸缘部、所述样品模块主体、所述辅助加热模块和所述密封件构成所述密闭空间；或者所述密封件具有第二凸缘部，所述第二凸缘部、所述样品模块、所述辅助加热模块和所述密封件构成所述密闭空间；或者所述密封件下面具有底板，所述底板、所述样品模块、所述辅助加热模块和所述密封件构成所述密闭空间。
本发明提供的PCR仪，包括如上所述的热循环装置。
本发明提供的热循环装置及PCR仪，具有以下有益效果：
本发明提供的热循环装置及PCR仪，包括：样品模块、加热制冷模块、散热模块、辅助加热模块及密封件；加热制冷模块设置于样品模块和散热模块之间，样品模块的周围设置辅助加热模块和密封件，辅助加热模块、密封件和样品模块构成密闭空间；辅助加热模块对密闭空间中的空气进行加热，加热后的空气对样品模块周围进行加热，从而可以对样品模块边缘的样品孔进行加热。因此，通过空气加热的方式使样品模块边缘的样品孔温度得到提升，并且 这种加热方式可以使加热更均匀，从而使样品模块的中间样品孔与边缘样品孔的温度更加均匀。
另外，本发明提供的热循环装置及PCR仪，还具有以下有益效果：
(1)本发明提供的热循环装置及PCR仪，还具有良好的保藏性能。通过对辅助加热模块、密封件和样品模块构成的密闭空间中的空气进行加热，使得密闭的空气得到加热后，与外界空气不流动，避免外界空气影响密闭空气的温度，从而使热循环装置及PCR仪具有良好的保藏功能，即便检测人员没有持续跟踪监测，当监测完成后，在辅助加热模块停止加热的情况下，密闭空气由于不受外界空气的影响，其温度能够保持一定的时间，因此可以将样品持续的保藏而不会失效变性。
(2)本发明提供的热循环装置及PCR仪，还可以提高加热制冷模块的寿命。具体的，上述由辅助加热模块、密封件和样品模块构成的密闭空间还可以隔离外界空气，减少外界空气带来的冷凝水对加热制冷模块的损坏，由于加热制冷模块通常需要采用电路板进行供电，因此可以防止冷凝水对电路板、加热制冷模块造成的短路影响，提高了加热制冷模块的寿命。
(3)在利用上述辅助加热模块对样品模块边缘的样品孔进行加热的基础上，将样品模块周围的辅助加热模块进行功率的特殊设计，即将辅助加热模块在样品模块周围的加热功率设置为不同功率，以便当样品模块周围的样品孔温度不同时，通过不同的加热功率使样品模块周围的样品孔温度更加均匀，从而在使样品模块的中间样品孔与边缘样品孔的温度更加均匀的同时，使样品模块不同区域的样品孔的温度进一步均匀。
具体的，样品模块周围包括进风口一侧、出风口一侧以及无风口侧，通常进风口一侧的样品孔温度小于出风口一侧的样品孔温度，出风口一侧的样品孔温度小于无风口侧的样品孔温度，因此，使进风口一侧的加热功率大于出风口一侧的加热功率，出风口一侧的加热功率大于无风口侧的加热功率，从而减小边缘上不同侧边处的样品孔之间的温度不均匀。从而使样品模块的多个区域的样品孔温度更加均匀，改善了PCR仪整体的基因扩增效果和检测性能的精准度及稳定性。
(4)在加热制冷模块和散热模块之间设置均热模块，使得样品模块各个区域的样品孔间的温度进一步均匀。
(5)在利用上述辅助加热模块对样品模块边缘的样品孔进行加热的基础 上，利用位于样品模块中间、具有一定散热性的螺钉，使得样品模块中间的样品孔温度得到降低，从而使样品模块中间样品孔的温度与边缘样品孔的温度进一步均匀；并且利用螺钉将样品模块、加热制冷模块和均热模块固定在散热器上，可以使加热制冷模块与样品模块以及均热模块之间有严密的贴合，具有一定的导热性，从而减小中间样品孔与边缘样品孔之间的温度不均匀。另外，螺钉还可以使加热制冷模块的受力更加均匀，从而在样品模块高、低温运行中，使加热制冷模块的形变量小，使得其寿命进一步加长。
本发明的其他特征和优点将在随后的说明书中阐述，并且，部分地从说明书中变得显而易见，或者通过实施本发明而了解。本发明的目的和其他优点在说明书、权利要求书以及附图中所特别指出的结构来实现和获得。
为使本发明的上述目的、特征和优点能更明显易懂，下文特举较佳实施例，并配合所附附图，作详细说明如下。
附图说明
为了更清楚地说明本发明具体实施方式或现有技术中的技术方案，下面将对具体实施方式或现有技术描述中所需要使用的附图作简单地介绍，显而易见地，下面描述中的附图是本发明的一些实施方式，对于本领域普通技术人员来讲，在不付出创造性劳动的前提下，还可以根据这些附图获得其他的附图。
图1为本发明实施例提供的热循环装置的截面示意图；
图2为本发明实施例提供的样品模块的示意图；
图3为本发明实施例提供的另一热循环装置的截面示意图；
图4为本发明实施例提供的热循环装置的正面示意图；
图5为本发明实施例提供的散热模块的示意图。
图标：1-样品模块；2-加热制冷模块；3-散热模块；4-辅助加热模块；41-辅助加热板；42-辅助加热膜；5-密封件；6-密闭空间；7-样品孔；8-均热模块；9-进风口一侧；10-出风口一侧；11-无风口侧；12-螺钉；13-装饰板；14-压条；15-电路板；16-质量减轻孔；17-区段；18-进风部；19-出风部；20-风扇；21-热界面材料。
具体实施方式
下面将结合实施例对本发明的技术方案进行清楚、完整地描述，显然，所描述的实施例是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。
目前市场的PCR基因扩增仪，其样品模块机构均采用整体材料精加工或铸造而成，都存在模块机构的边缘效应，即存在中间样品孔与边缘样品孔之间的热均匀性差及升降温速度不一致的现象，使得中间样品孔温度大高于边缘样品孔温度，导致样品模块的不同区域的样品孔温度不均匀。基于此，本发明实施例提供的热循环装置及PCR仪，通过空气加热的方式使样品模块边缘的样品孔温度得到提升，并且这种加热方式可以使加热更均匀，从而使样品模块的中间样品孔与边缘样品孔的温度更加均匀。
为便于对本实施例进行理解，首先对本发明实施例公开的一种热循环装置及PCR仪进行详细介绍。
图1示出了本发明实施例提供的热循环装置的示意图。
如图1所示，本发明实施例提供的热循环装置，包括：样品模块1、加热制冷模块2、散热模块3、辅助加热模块4及密封件5；加热制冷模块2设置于样品模块1和散热模块3之间，样品模块1的周围设置辅助加热模块4和密封件5，辅助加热模块4、密封件5和样品模块1构成密闭空间6；辅助加热模块4对密闭空间6中的空气进行加热，加热后的空气对样品模块1周围进行加热。
具体的，样品模块1包括承载样品的PCR孔板，PCR孔板上设有多个样品孔7。其中，样品孔7的数量不限定，例如为12孔、24孔、48孔、96孔、192孔或384等等，并且样品孔7的排布方式也不限定，通常的样品孔7排布成矩形。例如，可以为8×12阵列或者12×8阵列的96孔，或者16×24阵列的384孔，或者8×6阵列或16×3阵列的48孔等等。另外，样品模块1可以分为多个区段，每个区段包括多个样品孔7。
示例性的，如图2所示，样品模块1包括样品组块区段，该样品组块区段分为6个区段17，每个区段17包括用于形成样品孔7的凹部，形成16个样品孔7，一共96个样品孔7，排布成矩形，该样品孔7中用于盛放热循环的 样品。另外，样品组块区段上的样品孔7之间还可以设置质量减轻孔16，该质量减轻孔16从组块上移除质量，以便减轻样品组块区段的热质量。
本实施例中，加热制冷模块2可以包括加热制冷片，对样品模块1进行加热或降温；散热模块3可以采用散热器，对样品模块1进行散热；密封件5可以采用由橡胶等材料制成的密封垫。示例性的，如图1和图3所示，样品模块1的底面上可以设置加热制冷模块2，加热制冷模块2下面可以设置散热模块3。具体的，样品模块1还包括装饰板13，密封件5可以设置在装饰板13下面，由辅助加热模块4、密封件5和样品模块1形成密闭空间6，密闭空间6中的空气可以直接与样品模块1接触。其中，加热制冷模块2还包括电路板15，通过电路板15对加热制冷片供电。另外，如图4所示，样品模块1还可以通过压条14与加热制冷模块2进行固定。
由于加热制冷模块2对样品模块1加热时，存在边缘效应，即边缘样品孔与周围的空气接触使得温度降低，导致样品模块1的中间样品孔的温度高于边缘样品孔的温度，因此，本实施例利用加热辅助模块对样品模块1周围的密闭空间6中的空气进行加热，加热后的空气对样品模块1边缘的样品孔加热，通过空气加热的方式使样品模块1边缘的样品孔温度得到提升，并且这种加热方式可以使加热更均匀，从而使样品模块1的中间样品孔与边缘样品孔的温度更加均匀。
另外，上述密闭空间6使得密闭的空气得到加热后，与外界空气不流动，有良好的保温效果，从而使热循环装置具有良好的保藏功能；所以，即便检测人员没有持续跟踪监测，如检测过程中检测人员外出或者下班，当监测完成后，加热后的密闭空气可以将样品持续的保藏而不会失效变性。并且，密闭空间6还可以使外界空气隔离，减少外界空气带来的冷凝水，防止冷凝水对加热制冷模块2造成的损坏，例如防止对加热制冷模块2的电路板和加热制冷片造成短路，提高了加热制冷模块2的寿命。
在可选的实施方式中，辅助加热模块4在样品模块1周围的加热功率不同，通常的，样品模块1周围的样品孔温度可能会不同，通过将辅助加热模块4不同的位置设置为不同的加热功率，可以使样品模块1周围的样品孔温度更加均匀。
具体的，辅助加热模块4可以设置在样品模块1的四周。由于散热模块3 通过与外界风对流换热，起到对样品模块1散热降温的作用，如图4和图5所示，散热模块3包括进风部18和出风部19，相应的，样品模块1包括进风口一侧9、出风口一侧10和无风口侧11。外界风从散热模块3的进风部18进入，从其相对的出风部19排出，由于外界风开始进入散热模块3时，能使样品模块1的进风口一侧9快速降温，到了散热模块3后段，部分外界风在对流换热后温度有所升高，对样品模块1后段(出风口一侧10)的散热效果不明显，导致整个模块散热不均匀，进风口一侧9和出风口一侧10温度差异明显，导致进风口一侧9的样品孔温度小于出风口一侧10的样品孔温度，出风口一侧10的样品孔温度小于无风口侧11的样品孔温度。
本实施例针对上述问题，将样品模块1的四周的加热功率设置为：进风口一侧9的加热功率大于出风口一侧10的加热功率，出风口一侧10的加热功率大于无风口侧11的加热功率。从而减小边缘上不同侧边处的样品孔之间的温度不均匀。从而使样品模块1的多个区域的样品孔温度更加均匀，改善了PCR仪整体的基因扩增效果和检测性能的精准度及稳定性。
在实际应用中，如图5所示，为了提高散热模块3的散热效率，可以将风扇20置于散热模块3的一侧(进风部18)，但这样会进一步造成散热模块3进出风部19的温度差变大，进而造成样品模块1进风口一侧9和出风口一侧10温度差异更明显，通过将样品模块1四周的加热功率设置为上述不同加热功率，可以减小边缘上不同侧边处的样品孔之间的温度不均匀。
由上可知，目前的PCR仪将样品模块1的边缘效应与上述不同侧的温度差异进行叠加，会造成样品模块1的温度分布为：中间区域温度＞无风口侧温度＞出风口一侧温度＞进风口一侧温度。本实施例为了提高温度均匀性，在样品模块1周围增加了辅助加热模块4，从而使样品模块的中间样品孔与边缘样品孔的温度更加均匀。考虑到样品模块1四周的温度存在差异，因此将辅热加热模块的四个侧边的功率设计为不同功率，使进风口一侧的加热功率＞出风口一侧的加热功率＞无风口侧的加热功率，以此补偿样品模块1四周样品孔的温度不均匀，在使中间样品孔与边缘样品孔的温度更加均匀的情况下，进一步使样品模块1四周样品孔的温度更加均匀，达到比较好的温度均匀性。
在可选的实施方式中，如图1所示，上述辅助加热模块4包括辅助加热膜42和辅助加热板41，辅助加热膜42设置在辅助加热板41上。该辅助加热板 41具体可以采用铝板，辅助加热膜42通过胶或其他方式设置在铝板上面，辅助加热膜42对铝板进行加热，加热后的铝板加热密闭空间6中的空气，由于空气是密闭的，利用空气的传递使得密闭空间6有一定的温度。由于空气可以使热量在密闭空间6内传递的更均匀，而且密闭空气是直接与样品模块1一侧接触的，使样品模块1周围环境温度提高，从而使密闭空气能将样品模块1的边缘样品孔7均匀加热，减小边缘样品孔7与中间样品孔7的温度差距，提高样品模块1的温度均匀性。
上述辅助加热膜可以包括多片不同加热功率的加热膜，分别设置在样品模块的周围，使得进风口一侧的加热功率＞出风口一侧的加热功率＞无风口侧的加热功率。
上述辅助加热膜除了可以采用多片不同加热功率的加热膜外，还可以采用一片加热膜，通过将其加热丝的排布密度设置为不同，来补偿样品模块1四周样品孔的温度不均匀，具体可以将加热丝的排布密度设置为：进风口一侧的排布密度＞出风口一侧的排布密度＞无风口侧的排布密度。在可选的实施方式中，在将样品模块1的周围设置一圈的辅助加热模块4和密封件5，使得辅助加热模块4、密封件5和样品模块1共同构成密闭空间6的情况下，可以使密闭空间6在样品模块1的四周形成至少一个独立密闭空间，也就是说，密闭空间6可以是一圈连通的密闭空间，即一个独立密闭空间；也可以将样品模块1的一个侧边设置为独立密闭空间，其他三个侧边为连通的密闭空间，形成两个独立密闭空间；或者还可以将两个侧边设置为独立密闭空间，其他两个侧边为连通的密闭空间，形成三个独立密闭空间；或者作为优选的方式，将样品模块1四个侧边的密闭空间之间都隔离开来，形成四个独立密闭空间，使独立密闭的四个侧边密闭空间共同构成辅助加热空间。
优选的，当密闭空间6形成四个独立密闭空间时，这四个独立密闭空间之间的空气不流动，不同加热功率的辅助加热模块4加热对应侧边的密闭空间，可以使样品模块1不同侧边的边缘样品孔温度更快速的变得均匀。
需要说明的是，当密闭空间6形成一个独立密闭空间、两个独立密闭空间或者三个独立密闭空间时，虽然样品模块1不同侧边的空气之间可能会有流动，但位于不同侧边的不同加热功率的辅助加热模块4距离自身所在一侧的样品模块1更近，将自身所在一侧的空气加热后可以直接加热该侧的样品模块1， 从而可以使样品模块1不同侧边的样品孔温度变均匀。
上述密闭空间6由样品模块1、辅助加热模块4和密封件5构成的方式可以有多种，例如为以下构成方式(1)、(2)或者(3)：
(1)样品模块1的底面具有朝向密封件5的第一凸缘部，并且该第一凸缘部与密封件5紧密贴合，使得第一凸缘部、样品模块主体、辅助加热模块4和密封件5可以构成密闭空间6。
(2)密封件5具有朝向样品模块1的第二凸缘部，并且该第二凸缘部与样品模块1紧密贴合，使得第二凸缘部、样品模块1、辅助加热模块4和密封件5可以构成密闭空间6。
(3)密封件5下面具有底板，该底板与密封件5和样品模块1紧密贴合，使得底板、样品模块1、辅助加热模块4和密封件5可以构成密闭空间6。具体的，上述底板可以作为加强件或者其他功能部件，例如，底板还可以是上述电路板15，在此不做限制。
上述构成方式并不作为限制，只要能够使样品模块1、辅助加热模块4和密封件5构成密闭空间就可以。
在可选的实施方式中，热循环装置还包括均热模块8，均热模块8可以设置在加热制冷模块2和散热模块3之间。示例性的，如图3所示，加热制冷模块2的底面上设置均热模块8，均热模块8的底面设置在散热模块3上。具体的，均热模块8可以采用均热板，均热板内可以设置均温腔结构，均温腔结构包括真空腔体。
由于均热板具有极高的热传导效率，因此，通过在加热制冷模块2与散热模块3之间增加均热板，可以保证加热制冷模块2的温度均匀性，进而提升了样品模块1的动态温度均匀性。
在可选的实施方式中，如图2和图3所示，热循环装置还包括螺钉12，螺钉12可以设置在样品模块1的中间，并且螺钉12穿过样品模块1、加热制冷模块2和均热模块8，固定在散热模块3上，其导热系数在40-50W/m.K之间。具体可以在样品模块1中间设置用于安装螺钉12的多个孔。
在实际应用中，样品模块1通常分为多个区段17，每个区段17包括多个样品孔7，可以将螺钉12设置在每个区段17的中央，如图2所示。
具体的，螺钉12可以由高导热高散热性能的材料制作，如铝等等，由于其导热系数在40-50W/m.K之间，从而具有良好的导热性。在上述辅助加热模块对样品模块边缘的样品孔进行加热的基础上，螺钉12可以将其所在的样品模块1中间的样品孔7的温度降低，从而进一步减小中间样品孔7与边缘样品孔7的温度差异，提高样品模块1的温度均匀性。并且，螺钉12穿过样品模块1、加热制冷模块2、均热模块8、最终固定在散热模块3上，使得上述多个部件能够更好的固定。
另外，加热制冷模块2通常采用加热制冷片，由于加热制冷片比较长，容易存在弯曲，造成与样品模块1以及均热模块8之间贴合不好，影响导热性，并且使得加热制冷模块2需要较高的功率才能升温。
而本实施例中，一方面，样品模块1中间的螺钉12可以使加热制冷模块2与样品模块1以及均热模块8之间有严密的贴合，使得导热效果好，以便将加热制冷模块2的热量更快的传递出来，能够使样品模块1的温度更加均匀，不需要加热制冷模块2具有较高的功率。另一方面，螺钉12还可以使加热制冷模块2的受力更加均匀，在样品模块1高、低温运行中，使得加热制冷模块2形变量小，从而提高加热制冷模块2的寿命。
在可选的实施方式中，如图3所示，加热制冷模块2和样品模块1之间设有热界面材料21。具体的，可以在加热制冷模块2的顶面和样品模块1的底面之间设置热界面材料21，例如，热界面材料21为碳膜等导热材料，从而提高加热制冷模块2和样品模块1之间的导热性。
另外，加热制冷模块2和均热模块8之间也可以设置热界面材料，从而提高加热制冷模块2和均热模块8之间的导热性。本发明实施例提供的热循环装置，包括：样品模块、加热制冷模块、散热模块、辅助加热模块及密封件；加热制冷模块设置于样品模块和散热模块之间，样品模块的周围设置辅助加热模块和密封件，辅助加热模块、密封件和样品模块构成密闭空间；辅助加热模块对密闭空间中的空气进行加热，加热后的空气对样品模块周围进行加热，从而可以对样品模块边缘的样品孔进行加热。因此，通过空气加热的方式使样品模块边缘的样品孔温度得到提升，并且这种加热方式可以使加热更均匀，从而使样品模块的中间样品孔与边缘样品孔的温度更加均匀。
另外，本发明实施例提供的热循环装置，还具有以下优点：
(1)具有良好的保藏性能。通过对辅助加热模块、密封件和样品模块构成的密闭空间中的空气进行加热，使得密闭的空气得到加热后，与外界空气不流动，避免外界空气影响密闭空气的温度，从而使热循环装置及PCR仪具有良好的保藏功能，即便检测人员没有持续跟踪监测，当监测完成后，在辅助加热模块停止加热的情况下，密闭空气由于由于不受外界空气的影响，其温度能够保持一定的时间，因此，可以将样品持续的保藏而不会失效变性。
(2)提高加热制冷模块的寿命。具体的，上述由辅助加热模块、密封件和样品模块构成的密闭空间还可以隔离外界空气，减少外界空气带来的冷凝水对加热制冷模块的损坏，由于加热制冷模块通常需要采用电路板进行供电，因此可以防止冷凝水对电路板、加热制冷模块造成的短路影响，提高了加热制冷模块的寿命。
(3)在利用上述辅助加热模块对样品模块边缘的样品孔进行加热的基础上，将样品模块周围的辅助加热模块进行功率的特殊设计，即将辅助加热模块在样品模块周围的加热功率设置为不同功率，以便当样品模块周围的样品孔温度不同时，通过不同的加热功率使样品模块周围的样品孔温度更加均匀，从而在使样品模块的中间样品孔与边缘样品孔的温度更加均匀的同时，使样品模块不同区域的样品孔的温度进一步均匀。
具体的，使进风口一侧的加热功率大于出风口一侧的加热功率，出风口一侧的加热功率大于无风口侧的加热功率，从而减小边缘上不同侧边处的样品孔之间的温度不均匀。从而使样品模块的多个区域的样品孔温度更加均匀，改善了PCR仪整体的基因扩增效果和检测性能的精准度及稳定性。
(4)在加热制冷模块和散热模块之间设置均热模块，使得样品模块各个区域的样品孔间的温度进一步均匀。
(5)在利用上述辅助加热模块对样品模块边缘的样品孔进行加热的基础上，利用位于样品模块中间、具有一定散热性的螺钉，使得样品模块中间的样品孔温度得到降低，减小中间样品孔与边缘样品孔的温度差异，从而使样品模块中间样品孔的温度与边缘样品孔的温度进一步均匀；并且利用螺钉将样品模块、加热制冷模块和均热模块固定在散热器上，可以使加热制冷模块与样品模块以及均热模块之间有严密的贴合，具有一定的导热性，从而减小中间样品孔与边缘样品孔之间的温度不均匀。另外，螺钉还可以使加热制冷模块的受力更 加均匀，从而在样品模块高、低温运行中，使加热制冷模块的形变量小，使得其寿命进一步加长。
本发明实施例还提供一种PCR仪，该PCR仪包括如上的热循环装置。
具体的，PCR仪上设置有上述实施例的热循环装置，其中，样品模块上的样品孔中放置待测样品，通常为盛有试液的试管，在PCR仪检测过程中，需要对待测样品进行加热和冷却，以满足其反应温度，而热循环装置可以保证样品孔的温度均匀，即待测样品的温度均匀，从而得到均匀的样品产率。
本发明实施例的PCR仪具有温度均匀、质轻、升降温速度快、功率要求低等特性，大大的改善了仪器整体的基因扩增效果和检测性能的精准度及稳定性。
所属领域的技术人员可以清楚地了解到，为描述的方便和简洁，上述PCR仪的具体工作过程，可以参考前述热循环装置实施例中的具体实施过程，在此不再赘述。
另外，在本发明实施例的描述中，除非另有明确的规定和限定，术语“安装”、“相连”、“连接”应做广义理解，例如，可以是固定连接，也可以是可拆卸连接，或一体地连接；可以是机械连接，也可以是电连接；可以是直接相连，也可以通过中间媒介间接相连，可以是两个元件内部的连通。对于本领域的普通技术人员而言，可以具体情况理解上述术语在本发明中的具体含义。
在本发明的描述中，需要说明的是，术语“中心”、“上”、“下”、“左”、“右”、“竖直”、“水平”、“内”、“外”等指示的方位或位置关系为基于附图所示的方位或位置关系，仅是为了便于描述本发明和简化描述，而不是指示或暗示所指的装置或元件必须具有特定的方位、以特定的方位构造和操作，因此不能理解为对本发明的限制。
在本申请所提供的几个实施例中，应该理解到，所揭露的装置可以通过其它的方式实现。以上所描述的装置实施例仅仅是示意性的，例如，所述单元的划分，仅仅为一种逻辑功能划分，实际实现时可以有另外的划分方式，又例如，多个单元或组件可以结合或者可以集成到另一个系统，或一些特征可以忽略，或不执行。另一点，所显示或讨论的相互之间的耦合或直接耦合或通信连接可以是通过一些通信接口，装置或单元的间接耦合或通信连接，可以是电性，机械或其它的形式。
所述作为分离部件说明的单元可以是或者也可以不是物理上分开的，作为单元显示的部件可以是或者也可以不是物理单元，即可以位于一个地方，或者也可以分布到多个网络单元上。可以根据实际的需要选择其中的部分或者全部单元来实现本实施例方案的目的。
另外，在本发明各个实施例中的各功能单元可以集成在一个处理单元中，也可以是各个单元单独物理存在，也可以两个或两个以上单元集成在一个单元中。
所述功能如果以软件功能单元的形式实现并作为独立的产品销售或使用时，可以存储在一个处理器可执行的非易失的计算机可读取存储介质中。基于这样的理解，本发明的技术方案本质上或者说对现有技术做出贡献的部分或者该技术方案的部分可以以软件产品的形式体现出来，该计算机软件产品存储在一个存储介质中，包括若干指令用以使得一台计算机设备(可以是个人计算机，服务器，或者网络设备等)执行本发明各个实施例所述方法的全部或部分步骤。
最后应说明的是：以上所述实施例，仅为本发明的具体实施方式，用以说明本发明的技术方案，而非对其限制，本发明的保护范围并不局限于此，尽管参照前述实施例对本发明进行了详细的说明，本领域的普通技术人员应当理解：任何熟悉本技术领域的技术人员在本发明揭露的技术范围内，其依然可以对前述实施例所记载的技术方案进行修改或可轻易想到变化，或者对其中部分技术特征进行等同替换；而这些修改、变化或者替换，并不使相应技术方案的本质脱离本发明实施例技术方案的精神和范围，都应涵盖在本发明的保护范围之内。因此，本发明的保护范围应以所述权利要求的保护范围为准。

Claims (10)

  1. 一种热循环装置，其特征在于，包括：样品模块、加热制冷模块、散热模块、辅助加热模块及密封件；
    所述加热制冷模块设置于所述样品模块和所述散热模块之间，所述样品模块的周围设置所述辅助加热模块和所述密封件，所述辅助加热模块、所述密封件和所述样品模块构成密闭空间；
    所述辅助加热模块对所述密闭空间中的空气进行加热，加热后的空气对所述样品模块周围进行加热。
  2. 根据权利要求1所述的热循环装置，其特征在于，所述辅助加热模块在所述样品模块周围的加热功率不同。
  3. 根据权利要求2所述的热循环装置，其特征在于，所述样品模块周围包括进风口一侧、出风口一侧以及无风口侧，所述进风口一侧的加热功率大于所述出风口一侧的加热功率，所述出风口一侧的加热功率大于所述无风口侧的加热功率。
  4. 根据权利要求1所述的热循环装置，其特征在于，所述密闭空间在所述样品模块的四周形成至少一个独立密闭空间。
  5. 根据权利要求1所述的热循环装置，其特征在于，还包括均热模块，所述均热模块设置在所述加热制冷模块和所述散热模块之间。
  6. 根据权利要求5所述的热循环装置，其特征在于，还包括螺钉，所述螺钉设置在所述样品模块的中间，并且穿过所述样品模块、所述加热制冷模块和所述均热模块，固定在所述散热模块上；所述螺钉的导热系数在40-50W/m.K之间。
  7. 根据权利要求6所述的热循环装置，其特征在于，所述样品模块分为多个区段，每个所述区段包括多个样品孔，所述螺钉设置在每个所述区段的中央。
  8. 根据权利要求1所述的热循环装置，其特征在于，所述辅助加热模块包括辅助加热膜和辅助加热板，所述辅助加热膜设置在所述辅助加热板上。
  9. 根据权利要求1所述的热循环装置，其特征在于，所述样品模块的底面具有第一凸缘部，所述第一凸缘部、所述样品模块主体、所述辅助加热模块和所述密封件构成所述密闭空间；或者所述密封件具有第二凸缘部，所述第二 凸缘部、所述样品模块、所述辅助加热模块和所述密封件构成所述密闭空间；或者所述密封件下面具有底板，所述底板、所述样品模块、所述辅助加热模块和所述密封件构成所述密闭空间。
  10. 一种PCR仪，其特征在于，包括如权利要求1-9任一项所述的热循环装置。
PCT/CN2020/092543 2020-03-10 2020-05-27 热循环装置及pcr仪 WO2021179442A1 (zh)

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