Temperature control device and droplet type digital PCR instrument
By combining a flexible membrane with a vacuum mechanism, the problems of high thermal resistance and uneven temperature distribution at the droplet contact surface in microdroplet digital PCR instruments are solved, achieving efficient heating and cooling rates and uniform temperature distribution, while reducing material costs.
Patent Information
- Application Number
- CN202520025173.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Utility models(China)
- Current Assignee / Owner
- Filing Date
- 2025-01-06
- Publication Date
- 2026-01-02
- Estimated Expiration
- 2035-01-06
AI Technical Summary
The use of rigid materials on the droplet contact surface of existing microdroplet digital PCR instruments results in high thermal resistance and heat capacity, low heating and cooling rates, uneven temperature distribution, and high material costs.
A temperature control device combining a flexible membrane and a vacuum mechanism is used. By evacuating the vacuum, the flexible membrane is tightly bonded to the heat-conducting plate, which reduces thermal resistance and heat capacity, increases the heating and cooling rate, and reduces material costs.
While ensuring the flatness of the droplet contact surface, it effectively reduces thermal resistance and heat capacity, increases the heating and cooling rate, ensures uniform temperature distribution, reduces material costs, and improves economic efficiency.
Smart Images
Figure CN223752801U_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The utility model relates to nucleic acid detection technical field, specifically, relate to a temperature control device and micro drop formula digital PCR appearance. BACKGROUND
[0002] Micro drop formula digital PCR is an absolute quantitative PCR technique, it mainly adopts micro drop method, disperses the solution containing target nucleic acid to a large number of water-in-oil droplets, forms ten thousand independent micro reaction systems of equal volume, and the initial target nucleic acid template number of each droplet is 0, 1 or multiple, so that after PCR cycle, the droplet with one target nucleic acid will give a fluorescent signal, and the droplet without target nucleic acid has no fluorescent signal, according to the relative proportion of two kinds of droplets and poisson distribution mathematical correction, the target nucleic acid concentration of original solution can be calculated.
[0003] Micro drop formula digital PCR needs to be heat cycled (the droplet is cycled by temperature control device), and it requires that the droplet contact surface is flat and horizontal to ensure that the droplets are closely arranged in the reaction pool without gravity flow. The micro drop formula digital PCR appearance now adopts hard material such as aluminum plate or glass plate with certain thickness (0.5mm-1mm) as droplet contact surface material to meet the requirement of flat droplet contact surface. However, in this way, first, the thicker contact surface has greater thermal resistance and heat capacity, which is not conducive to improving the temperature rising and falling rate; second, the thermal conductive surface of the droplet contact surface and the temperature control device is a solid material with high rigidity, even if the machining precision is high, the uneven contact condition can not be avoided, resulting in uneven temperature distribution at each position; third, in order to prevent cross contamination, the droplet contact surface is a disposable consumable, and the material cost of glass plate or aluminum plate is high.
[0004] Therefore, it is particularly important to design and manufacture a temperature control device and micro drop formula digital PCR appearance with high temperature rising and falling rate, uniform temperature distribution and low material cost, especially in nucleic acid detection. UTILITY MODEL CONTENTS
[0005] The utility model aims at providing a temperature control device, which can effectively reduce thermal resistance and heat capacity, improve temperature rising and falling rate, ensure uniform temperature distribution, reduce material cost and improve economic benefit under the condition of ensuring the flatness of droplet contact surface.
[0006] Another purpose of the utility model is to provide a micro drop formula digital PCR appearance, which can effectively reduce thermal resistance and heat capacity, improve temperature rising and falling rate, ensure uniform temperature distribution, reduce material cost and improve economic benefit under the condition of ensuring the flatness of droplet contact surface.
[0007] The utility model is implemented by adopting the following technical solutions.
[0008] A temperature control device comprises a base, a temperature control mechanism, a heat-conducting plate, a reaction disc and a vacuumizing mechanism, the temperature control mechanism is installed on the base and connected with the heat-conducting plate, the reaction disc is placed on the heat-conducting plate, the reaction disc comprises a disc body and a flexible film, the flexible film is connected to the bottom of the disc body, the flexible film is used for carrying the liquid droplet to be tested, the heat-conducting plate is provided with an air outlet hole, the vacuumizing mechanism is communicated with the air outlet hole, and the vacuumizing mechanism is used for extracting air between the flexible film and the heat-conducting plate, so that the flexible film is tightly attached to the heat-conducting plate.
[0009] Optionally, the reaction disc further comprises a flexible partition wall, the flexible partition wall is connected to the flexible film, and the flexible partition wall and the flexible film jointly form at least one accommodation groove for accommodating the liquid droplet to be tested.
[0010] Optionally, the heat-conducting plate is provided with an exhaust groove, and the air outlet hole is arranged on the bottom wall of the exhaust groove.
[0011] Optionally, the position of the flexible partition wall corresponds to the position of the exhaust groove.
[0012] Optionally, the heat-conducting plate is provided with a sealing groove, a sealing ring is arranged in the sealing groove, and the sealing ring abuts against the disc body.
[0013] Optionally, the temperature control mechanism comprises a temperature rising and falling element, a temperature sensor and a radiator, the temperature sensor is connected with the heat-conducting plate, the temperature sensor is used for detecting the real-time temperature of the heat-conducting plate, the temperature rising and falling element and the radiator are both installed on the base and connected with the heat-conducting plate, the temperature rising and falling element is used for heating or refrigerating the heat-conducting plate, and the radiator is used for cooling the heat-conducting plate.
[0014] Optionally, the vacuumizing mechanism comprises a vacuum pump, a three-way pipe and an air pressure sensor, the first end of the three-way pipe is connected with the air outlet hole, the second end of the three-way pipe is connected with the vacuum pump, the third end of the three-way pipe is connected with the air pressure sensor, the vacuum pump is used for extracting air outward, and the air pressure sensor is used for detecting the real-time vacuum degree.
[0015] Optionally, the temperature control device further comprises a positioning mechanism, the positioning mechanism comprises a positioning frame and a positioning piece, the positioning frame is installed on the base and simultaneously surrounds the heat-conducting plate and the disc body, the disc body is provided with a limiting groove, and the positioning piece is movably installed in the positioning frame and matched with the limiting groove.
[0016] Optionally, the positioning piece comprises an elastic piece and a ball, the positioning frame is provided with a positioning groove, one end of the elastic piece is connected with the bottom wall of the positioning groove, the other end is connected with the ball, and the ball is slidably arranged in the positioning groove; the limiting groove is conically arranged, the midpoint of the limiting groove is higher than the center of the ball, the ball is arranged to extend into the limiting groove and abut against the side wall of the limiting groove.
[0017] The micro-droplet digital PCR instrument comprises the temperature control device, and the temperature control device comprises a base, a temperature control mechanism, a heat conduction plate, a reaction disc and a vacuumizing mechanism.
[0018] The temperature control device and the micro-droplet digital PCR instrument have the following beneficial effects:
[0019] The temperature control device comprises the temperature control mechanism, the heat conduction plate, the reaction disc and the vacuumizing mechanism. Compared with the prior art, the temperature control device provided by the utility model has the flexible film connected to the bottom of the disc body and the vacuumizing mechanism communicated with the air exhaust hole, so that the thermal resistance and the heat capacity can be effectively reduced under the condition of ensuring the flatness of the liquid droplet contact surface, the temperature rising and falling rate is improved, the temperature distribution is uniform, the material cost is reduced, and the economic benefit is improved.
[0020] The micro-droplet digital PCR instrument comprises the temperature control device, and the temperature control device comprises a base, a temperature control mechanism, a heat conduction plate, a reaction disc and a vacuumizing mechanism. BRIEF DESCRIPTION OF DRAWINGS
[0021] In order to more clearly illustrate the technical scheme of the utility model embodiment, the following will be briefly introduced the drawings needed to be used in the embodiment, and it should be understood that the following drawings only show some embodiments of the utility model, and therefore should not be regarded as the limitation to the scope, and for the ordinary skilled in the art, other related drawings can be obtained without the creative labor under the premise.
[0022] Figure 1 The structure schematic view of the temperature control device provided by the utility model embodiment is shown in the figure.
[0023] Figure 2 The structure schematic view of the temperature control mechanism and the base connection in the temperature control device provided by the utility model embodiment is shown in the figure.
[0024] Figure 3 The explosion view of the temperature control mechanism and the base connection in the temperature control device provided by the utility model embodiment is shown in the figure.
[0025] Figure 4 A structure schematic view of the vacuumizing mechanism in the temperature control device is provided for the embodiment of the utility model;
[0026] Figure 5 An exploded view of the reaction disc in the temperature control device is provided for the embodiment of the utility model;
[0027] Figure 6 A structure schematic view of the reaction disc in the temperature control device is provided for the embodiment of the utility model;
[0028] Figure 7 A structure schematic view of the heat conduction plate in the temperature control device is provided for the embodiment of the utility model;
[0029] Figure 8 A partial sectional view of the heat conduction plate in the temperature control device is provided for the embodiment of the utility model;
[0030] Figure 9 An exploded view of the reaction disc and the positioning mechanism cooperation in the temperature control device is provided for the embodiment of the utility model;
[0031] Figure 10 A sectional view of the reaction disc and the positioning mechanism cooperation in the temperature control device is provided for the embodiment of the utility model.
[0032] Icon: 100-temperature control device;110-base;120-temperature control mechanism;121-temperature change element;122-temperature sensor;123-radiator;130-heat conduction plate;131-exhaust hole;1311-extension section;1312-exhaust section;132-exhaust groove;1321-cross groove;1322-longitudinal groove;133-heat transfer area;134-sealing groove;140-reaction disc;141-disc body;1411-limiting groove;142-flexible film;143-flexible partition;1431-cross strip;1432-longitudinal strip;144-housing groove;150-vacuumizing mechanism;151-vacuum pump;152-three-way pipe;153-air pressure sensor;160-sealing ring;170-positioning mechanism;171-positioning frame;1711-positioning groove;172-positioning piece;1721-elastic piece;1722-pearl. DETAILED DESCRIPTION
[0033] In order to make the purpose, technical scheme and advantages of the embodiment of the utility model more clear, the technical scheme in the embodiment of the utility model will be described clearly and completely below by combining with the drawings in the embodiment of the utility model, obviously, the described embodiment is a part of the embodiment of the utility model, not all the embodiments. The components of the embodiment of the utility model described and shown in the drawings here can be arranged and designed in various different configurations.
[0034] Therefore, the following detailed description of the embodiments of the application provided in the drawings is not intended to limit the scope of the claimed application, but merely represents selected embodiments of the application. Based upon these embodiments of the application, all other embodiments obtained by persons of ordinary skill in the art without creative work are within the scope of the application.
[0035] It should be noted that similar reference numbers and letters refer to similar items in the following drawings, and therefore, once an item is defined in one drawing, it need not be further defined and explained in subsequent drawings.
[0036] In the description of the application, it should be noted that the terms "inner", "outer", "upper", "lower", "horizontal", etc. indicate the orientation or positional relationship based on the orientation or positional relationship shown in the drawings, or the orientation or positional relationship in which the product of the application is usually placed, and are only for the convenience of describing the application and simplifying the description, and therefore cannot be understood as indicating or implying that the device or element must have a particular orientation, be constructed and operated in a particular orientation, and therefore cannot be understood as limiting the application. In addition, the terms "first", "second", "third", etc. are only used for differentiation, and cannot be understood as indicating or implying relative importance.
[0037] In the description of the application, it should also be noted that, unless otherwise explicitly specified and limited, the terms "provided", "connected", "mounted", "connected" should be broadly understood, for example, it can be fixedly connected, or it can be detachably connected, or integrally connected; it can be mechanically connected, or it can be electrically connected; it can be directly connected, or it can be indirectly connected through an intermediate medium, or it can be the communication between two elements inside. For ordinary skilled persons in the art, the specific meaning of the above terms in the application can be understood according to the specific circumstances.
[0038] Some embodiments of the application will be described in detail below with reference to the accompanying drawings. The features in the following embodiments can be combined with each other without conflict.
[0039] Please refer to Figures 1 to 8 The embodiment of the application provides a micro-droplet digital PCR instrument (not shown in the figure) for nucleic acid detection. It can effectively reduce the thermal resistance and heat capacity, improve the temperature rising and falling rate, ensure the uniformity of temperature distribution, reduce the material cost and improve the economic benefit under the condition of ensuring the flatness of the droplet contact surface.
[0040] The micro-droplet digital PCR instrument comprises a micro-droplet generating device (not shown in the figure), a temperature control device 100 and a microscopic shooting device (not shown in the figure). The micro-droplet generating device is used to make a large number of water-in-oil droplets (to-be-tested droplets) from the original solution in a sample and inject the to-be-tested droplets into the temperature control device 100; the temperature control device 100 is used to perform temperature rising and falling cycles on the to-be-tested droplets, and the number of target nucleic acids in each to-be-tested droplet is doubled after each temperature rising and falling cycle, and the process is repeated to greatly increase the number of trace target nucleic acids; the microscopic shooting device is used to shoot and calculate all the to-be-tested droplets after the temperature rising and falling cycles are completed, and the to-be-tested droplets with target nucleic acids will give a fluorescent signal, and the to-be-tested droplets without target nucleic acids will not give a fluorescent signal, and according to the relative proportion of the number of the two kinds of to-be-tested droplets and the Poisson distribution mathematical correction, the target nucleic acid concentration of the original solution in the corresponding sample can be calculated.
[0041] The temperature control device 100 comprises a base 110, a temperature control mechanism 120, a heat conduction plate 130, a reaction disc 140 and a vacuum pumping mechanism 150. The temperature control mechanism 120 is installed on the base 110 and connected with the heat conduction plate 130, the reaction disc 140 is placed on the heat conduction plate 130, the heat conduction plate 130 has good heat conduction effect, the reaction disc 140 is used to contain the to-be-tested droplets, and the temperature control mechanism 120 is used to heat or cool the reaction disc 140 through the heat conduction plate 130 to realize the temperature rising and falling function of the reaction disc 140, so as to perform temperature rising and falling cycles on the to-be-tested droplets.
[0042] Further, the reaction disc 140 comprises a disc body 141 and a flexible film 142. The bottom of the disc body 141 is hollowed, and the flexible film 142 is connected to the bottom of the disc body 141. The flexible film 142 is used to carry the liquid droplets to be tested, and the temperature control mechanism 120 is used to heat or cool the liquid droplets to be tested through the flexible film 142. Specifically, when the reaction disc 140 is normally placed on the heat conduction plate 130, there will inevitably be a gap between the heat conduction plate 130 and the flexible film 142, so that the heat conduction plate 130 and the flexible film 142 are not uniformly contacted, thereby causing the heat conduction plate 130 to not quickly and uniformly transfer heat to the flexible film 142. Therefore, the heat conduction plate 130 is provided with an air extraction hole 131, and the air extraction hole 131 is communicated with the air extraction mechanism 150. The air extraction mechanism 150 is used to extract the air between the flexible film 142 and the heat conduction plate 130, so that the flexible film 142 is tightly attached to the heat conduction plate 130, and the gap between the heat conduction plate 130 and the flexible film 142 is eliminated. In this way, on the one hand, the flexible film 142 can be laid on the heat conduction plate 130, and the flatness of the flexible film 142 is improved, so as to ensure the flatness of the liquid droplet contact surface. At this time, only the heat conduction plate 130 needs to be controlled to be in a horizontal state, so as to ensure the levelness of the liquid droplet contact surface, and ensure that the liquid droplets to be tested are closely arranged without flowing due to gravity. On the other hand, the thermal resistance and the heat capacity can be effectively reduced (the thickness of the flexible film 142 is relatively thin, and the thermal resistance and the heat capacity are far less than those of the glass plate or the aluminum plate), the heat transfer efficiency is improved, so as to improve the temperature rising and falling rate, and ensure uniform temperature distribution. On the other hand, the material cost can be reduced (the material cost of the flexible film 142 is far less than that of the glass plate or the aluminum plate), and the economic benefit is improved.
[0043] Preferably, the disc body 141 is made of plastic materials such as polypropylene, the flexible film 142 is made of materials such as aluminum foil, aluminum plastic film, polypropylene film or polyimide film, and the thickness is 0.025mm-0.05mm. The flexible film 142 has a relatively thin thickness and good flexibility. The base 110 is made of aluminum material, and is used as the structural support basis of the entire temperature control device 100. The heat conduction plate 130 is made of common high-thermal-conductivity materials such as aluminum, copper or silver, and has high heat conduction efficiency.
[0044] Specifically, the flexible film 142 is fixedly connected to the bottom of the disc body 141 by adhesion or heat melting, so as to ensure the sealing property and prevent liquid leakage. Since the thickness of the flexible film 142 is 1-2 orders of magnitude thinner than that of the glass plate or the aluminum plate in the prior art, the thermal resistance and the heat capacity can be greatly reduced, so as to achieve the purpose of improving the temperature rising and falling rate. Since the rigidity of the flexible film 142 is relatively low, after the air between the flexible film 142 and the heat conduction plate 130 is extracted by the air extraction mechanism 150, the flexible film 142 will be tightly attached to the heat conduction plate 130 under the action of the atmospheric pressure. Since the atmospheric pressure is uniform, the pressure at the contact surface between the flexible film 142 and the heat conduction plate 130 is equal everywhere, and the heat conduction uniformity is improved.
[0045] Preferably, the reaction disc 140 further comprises a flexible partition wall 143. The flexible partition wall 143 is connected to the flexible film 142, and is arranged on the upper surface of the flexible film 142. Since the flexible partition wall 143 is also flexible, it can deform along with the flexible film 142, and does not affect the close adhesion of the flexible film 142 and the heat conduction plate 130. Specifically, the flexible partition wall 143 and the flexible film 142 jointly form at least one accommodating groove 144, which is used for accommodating a to-be-tested liquid drop of a sample (each accommodating groove 144 is used for accommodating a to-be-tested liquid drop of a sample), and the flexible partition wall 143 is used for preventing the to-be-tested liquid drop from overflowing out of the accommodating groove 144, so as to avoid cross contamination of to-be-tested liquid drops of multiple samples.
[0046] Preferably, the flexible partition wall 143 is made of a flexible oil-resistant and heat-resistant material such as silica gel or rubber, and is fixedly connected to the flexible film 142 by bonding or hot melting, so as to completely seal the position where the bottom of the flexible partition wall 143 is connected to the flexible film 142, and prevent liquid channeling.
[0047] Further, the number of the accommodating grooves 144 is multiple, each accommodating groove 144 is used for accommodating a to-be-tested liquid drop of a sample, and the multiple accommodating grooves 144 jointly act to simultaneously realize temperature rising and falling cycles of to-be-tested liquid drops in multiple samples, so as to simultaneously realize nucleic acid detection of multiple samples, and improve the nucleic acid detection efficiency.
[0048] In this embodiment, the accommodating grooves 144 are arranged in a rectangular shape, the number of the accommodating grooves 144 is eight, and the eight accommodating grooves 144 are arranged in a rectangular array, so as to simultaneously realize nucleic acid detection of eight samples. However, this is not a limitation. In other embodiments, the accommodating grooves 144 can be arranged in a circular shape or a triangular shape, the number of the accommodating grooves 144 can be six or ten, and the shape and number of the accommodating grooves 144 are not limited.
[0049] Preferably, the heat conduction plate 130 is provided with an exhaust groove 132, the exhaust groove 132 is arranged on the upper surface of the heat conduction plate 130 and extends to each corner of the heat conduction plate 130, and the exhaust groove 132 is used for auxiliary exhaust, so as to ensure that the flexible film 142 can be closely adhered to the upper surface of the heat conduction plate 130. Specifically, the air suction hole 131 is arranged on the bottom wall of the exhaust groove 132, the vacuum suction mechanism 150 is in communication with the exhaust groove 132 through the air suction hole 131, and the vacuum suction mechanism 150 is used for sucking out air in the exhaust groove 132 through the air suction hole 131, so as to form a stable vacuum field between the heat conduction plate 130 and the flexible film 142, and ensure that the flexible film 142 is closely adhered to the heat conduction plate 130.
[0050] It should be noted that the exhaust groove 132 is a groove with small depth and small width, and the flexible film 142 has a certain rigidity, so the flexible film 142 will not stretch into the exhaust groove 132 and fit the inner wall of the exhaust groove 132 under the suction force of the vacuumizing mechanism 150, but will remain in the state of being attached to the upper surface of the heat conduction plate 130 to achieve higher flatness.
[0051] Preferably, the position of the flexible partition wall 143 corresponds to the position of the exhaust groove 132, that is, the position of the flexible partition wall 143 provided on the flexible film 142 is the same as the position of the exhaust groove 132 opened on the heat conduction plate 130, so as to ensure the temperature rising and falling rate of the droplet to be measured in the accommodation groove 144. Specifically, since the flexible film 142 will not fit the inner wall of the exhaust groove 132, the heat transfer efficiency of the heat conduction plate 130 to the flexible film 142 at the position of the exhaust groove 132 is low, and correspondingly, the flexible partition wall 143 on the flexible film 142 is used to block the droplets to be measured of adjacent two accommodation grooves 144, and the position of the flexible partition wall 143 itself does not have the droplet to be measured and does not need to be subjected to high-precision temperature regulation, so that the position of the flexible partition wall 143 corresponds to the position of the exhaust groove 132, which can not only improve the exhaust efficiency and ensure the vacuumizing effect, so as to ensure that the flexible film 142 is closely attached to the heat conduction plate 130, but also can avoid affecting the heat transfer efficiency to the droplet to be measured, and ensure the temperature rising and falling rate of the droplet to be measured.
[0052] In the embodiment, the flexible partition wall 143 includes three horizontal strips 1431 and five vertical strips 1432, wherein the three horizontal strips 1431 are arranged in parallel and at intervals, the five vertical strips 1432 are arranged in parallel and at intervals, each horizontal strip 1431 is connected with the five vertical strips 1432, each vertical strip 1432 is connected with the three horizontal strips 1431, and the horizontal strip 1431 is perpendicular to the vertical strip 1432 to jointly form eight accommodation grooves 144. Correspondingly, the exhaust groove 132 includes three horizontal grooves 1321 and five vertical grooves 1322, wherein the three horizontal grooves 1321 are arranged in parallel and at intervals, the five vertical grooves 1322 are arranged in parallel and at intervals, each horizontal groove 1321 is connected with the five vertical grooves 1322, each vertical groove 1322 is connected with the three horizontal grooves 1321, and the horizontal groove 1321 is perpendicular to the vertical groove 1322 to form eight heat transfer regions 133 on the upper surface of the heat conduction plate 130, and the positions of the eight heat transfer regions 133 correspond to the positions of the eight accommodation grooves 144 one by one, each heat transfer region 133 is used for heat transfer to the droplet to be measured in one accommodation groove 144 to realize the temperature rising and falling cycle operation.
[0053] Preferably, the heat-conducting plate 130 is provided with a sealing groove 134, which is arranged at the edge of the heat-conducting plate 130 and surrounds the eight heat transfer regions 133. A sealing ring 160 is arranged in the sealing groove 134 and abuts against the disc body 141. The sealing ring 160 is used to seal the gap between the disc body 141 and the heat-conducting plate 130, so as to improve the air tightness, ensure the stable vacuum field between the heat-conducting plate 130 and the flexible film 142, and ensure that the flexible film 142 is tightly attached to the heat-conducting plate 130. Specifically, the sealing ring 160 is made of high-temperature-resistant silica gel or rubber material.
[0054] The temperature control mechanism 120 includes a temperature sensing element 121, a temperature sensor 122 and a heat sink 123. The temperature sensor 122 is connected to the heat-conducting plate 130 and is used to detect the real-time temperature of the heat-conducting plate 130 and feed back to the controller to form a closed-loop temperature control and improve the temperature control accuracy. The temperature sensing element 121 and the heat sink 123 are both mounted on the base 110 and connected to the heat-conducting plate 130. The temperature sensing element 121 is used to heat or cool the heat-conducting plate 130, and the heat sink 123 is used to cool the heat-conducting plate 130. The controller can control the temperature sensing element 121 and the heat sink 123 according to the real-time temperature of the heat-conducting plate 130 to realize the temperature rising and falling cycle function of the liquid droplet to be measured.
[0055] In this embodiment, the temperature sensing element 121 is a Peltier element, and the heat sink 123 is a air-cooled heat sink. However, it is not limited thereto. In other embodiments, the temperature sensing element 121 can be a resistance sheet, and the heat sink 123 can be a water-cooled heat sink. The type of the temperature sensing element 121 and the heat sink 123 is not specifically limited.
[0056] The vacuum pumping mechanism 150 includes a vacuum pump 151, a three-way pipe 152 and a gas pressure sensor 153. The first end of the three-way pipe 152 is connected to the air outlet hole 131, the second end of the three-way pipe 152 is connected to the vacuum pump 151, and the third end of the three-way pipe 152 is connected to the gas pressure sensor 153. Specifically, the gas pressure sensor 153 is used to detect the real-time vacuum degree and feed back to the controller to form a closed-loop vacuum degree control and improve the vacuum pumping accuracy. The vacuum pump 151 is used to pump out air. The controller can control the vacuum pump 151 according to the real-time vacuum degree to ensure that a stable vacuum field is formed between the heat-conducting plate 130 and the flexible film 142, so as to ensure that the flexible film 142 is tightly attached to the heat-conducting plate 130.
[0057] In the embodiment, the air extraction hole 131 is divided into an extension section 1311 and an exhaust section 1312 which are perpendicular to each other and communicate with each other. The extension section 1311 is arranged within the range surrounded by the sealing groove 134. The depth of the sealing groove 134 is greater than the depth of the exhaust groove 132 and less than the depth of the extension section 1311. One end of the extension section 1311 communicates with the exhaust groove 132, and the other end communicates with the exhaust section 1312. The exhaust section 1312 is arranged beyond the sealing groove 134 and communicates with the three-way pipe 152. In this way, under the suction of the vacuum pump 151, the air between the heat conduction plate 130 and the flexible film 142 can be sequentially extracted outwards through the exhaust groove 132, the extension section 1311, the exhaust section 1312 and the three-way pipe 152, so as to ensure that the flexible film 142 is tightly attached to the heat conduction plate 130.
[0058] Please refer to Figure 9 and Figure 10 Preferably, the temperature control device 100 further comprises a positioning mechanism 170. The positioning mechanism 170 comprises a positioning frame 171 and a positioning piece 172. The positioning frame 171 is mounted to the base 110 and simultaneously surrounds the heat conduction plate 130 and the disc body 141 of the reaction disc 140. The base 110 is used to fix the position of the positioning frame 171, and the positioning frame 171 is used to limit the disc body 141, so as to ensure that the reaction disc 140 is aligned with the heat conduction plate 130 when placed, thereby ensuring that the positions of the eight heat transfer regions 133 correspond to the positions of the eight accommodating grooves 144 one by one. In addition, the positioning frame 171 can also play a heat preservation role, which isolates the temperature of the heat conduction plate 130 from the temperature of the external environment, ensures the heat transfer effect of the heat conduction plate 130 on the reaction disc 140, and improves the temperature rising and falling rate.
[0059] Further, the outer side wall of the disc body 141 is provided with a limiting groove 1411, and the positioning piece 172 is movably mounted to the positioning frame 171 and cooperates with the limiting groove 1411 to fix the relative positions of the disc body 141 and the positioning frame 171, thereby fixing the relative positions of the disc body 141 and the heat conduction plate 130, and facilitating subsequent vacuum extraction operation.
[0060] The positioning piece 172 comprises an elastic piece 1721 and a ball 1722. The positioning frame 171 is provided with a positioning groove 1711. One end of the elastic piece 1721 is connected to the bottom wall of the positioning groove 1711, and the other end is connected to the ball 1722. The ball 1722 is slidably arranged in the positioning groove 1711. The elastic piece 1721 is always in a compressed state to apply a elastic force to the ball 1722, so that the ball 1722 has a tendency to move out of the positioning groove 1711. Specifically, the limiting groove 1411 is conically arranged, and the ball 1722 extends into the limiting groove 1411 and abuts against the side wall of the limiting groove 1411, so as to fix the relative positions of the disc body 141 and the positioning frame 171 and prevent the disc body 141 from accidentally coming out of the positioning frame 171.
[0061] Preferably, the midpoint of the limiting groove 1411 is higher than the center of the ball 1722, that is, the axis of the conical limiting groove 1411 is higher than the center of the ball 1722. Due to the higher axis of the conical limiting groove 1411, the ball 1722 will exert a vertical downward component force on the side wall of the limiting groove 1411 under the action of the elastic member 1721, which will promote the downward movement of the disc body 141 and make it closely contact with the sealing ring 160, so as to further improve the air tightness and ensure the stable vacuum field between the heat conduction plate 130 and the flexible film 142.
[0062] In the embodiment, the elastic member 1721 is a spring and the ball 1722 is a steel ball. However, it is not limited to this, in other embodiments, the elastic member 1721 can be an elastic rubber and the ball 1722 can be an aluminum ball. The material of the elastic member 1721 and the ball 1722 is not specifically limited. In addition, the elastic member 1721 and the ball 1722 can be combined into one part, and the ball 1722 is driven to move by the elasticity of the elastic member 1721 (plastic or metal).
[0063] In the embodiment, the positioning is achieved by the cooperation of the ball 1722 and the conical limiting groove 1411. However, it is not limited to this, in other embodiments, the positioning can also be achieved by the cooperation of a wedge-shaped block and an inclined groove. The positioning mode of the positioning member 172 is not specifically limited.
[0064] Further, the number of the elastic member 1721, the ball 1722, the positioning groove 1711 and the limiting groove 1411 is multiple. Each elastic member 1721 is connected with a ball 1722 and arranged in a positioning groove 1711. Each ball 1722 can extend into a limiting groove 1411. The multiple limiting grooves 1411 are arranged on the outer side wall of the disc body 141. The multiple elastic members 1721, the multiple balls 1722, the multiple positioning grooves 1711 and the multiple limiting grooves 1411 jointly act to further improve the limiting effect and fix the relative position of the disc body 141 and the positioning frame 171.
[0065] In the embodiment, the number of the elastic member 1721, the ball 1722, the positioning groove 1711 and the limiting groove 1411 is four. Among them, two limiting grooves 1411 are arranged on one side of the disc body 141, and the other two limiting grooves 1411 are arranged on the other side of the disc body 141. However, it is not limited to this, in other embodiments, the number of the elastic member 1721, the ball 1722, the positioning groove 1711 and the limiting groove 1411 can be six or eight. The number of the elastic member 1721, the ball 1722, the positioning groove 1711 and the limiting groove 1411 is not specifically limited.
[0066] It should be noted that, in the use process of the temperature control device 100, first, the reaction disc 140 is placed on the heat conduction plate 130, and in this process, the positioning frame 171 limits the reaction disc 140 to ensure that the placement position of the reaction disc 140 is aligned with the position of the heat conduction plate 130, and the positioning member 172 positions the reaction disc 140 by cooperating with the limiting groove 1411 to fix the relative position of the reaction disc 140 and the positioning frame 171; then the vacuum pumping mechanism 150 is started to pump out the air between the flexible film 142 and the heat conduction plate 130, so that the flexible film 142 is closely attached to the heat conduction plate 130; then the liquid droplet to be measured is injected into the reaction disc 140; then the temperature control mechanism 120 is started to perform temperature rising and falling cycle operation on the liquid droplet to be measured in the reaction disc 140, facilitating subsequent observation and calculation, thereby realizing the nucleic acid detection function.
[0067] The temperature control device 100 provided by the embodiment of the utility model, the temperature control mechanism 120 is installed in the base 110, and is connected with the heat conduction plate 130, the reaction disc 140 is placed on the heat conduction plate 130, the reaction disc 140 includes disc body 141 and flexible film 142, the flexible film 142 is connected to the bottom of disc body 141, the flexible film 142 is used for bearing the liquid droplet to be measured, the heat conduction plate 130 is provided with air hole 131, the vacuum pumping mechanism 150 is communicated with air hole 131, and the vacuum pumping mechanism 150 is used for pumping out the air between the flexible film 142 and the heat conduction plate 130, so that the flexible film 142 is closely attached to the heat conduction plate 130. Compared with the prior art, the temperature control device 100 provided by the utility model can effectively reduce the thermal resistance and the heat capacity, improve the temperature rising and falling rate, ensure the uniform temperature distribution, reduce the material cost and improve the economic benefit under the condition of ensuring the flatness of the liquid droplet contact surface. The micro-droplet digital PCR instrument has high detection efficiency and good detection effect.
[0068] The above is only the preferred embodiment of the utility model, and is not used for limiting the utility model. For those skilled in the art, the utility model can have various changes and changes. Any modification, equivalent replacement, improvement, etc. made within the spirit and principles of the utility model shall be included in the protection scope of the utility model.
Claims
1. A temperature control device, characterized by, The reaction disc further comprises a flexible partition wall connected to the flexible film, the flexible partition wall and the flexible film jointly form at least one accommodating groove for accommodating the liquid droplet to be tested.
2. The temperature control device of claim 1, wherein The heat-conducting plate is provided with an exhaust groove, and the air exhaust hole is arranged at the bottom wall of the exhaust groove.
3. The temperature control device of claim 2, wherein, The position of the flexible partition wall corresponds to the position of the exhaust groove.
4. The temperature control device of claim 3, wherein The heat-conducting plate is provided with a sealing groove, and a sealing ring is arranged in the sealing groove and abuts against the disc body.
5. The temperature control device of claim 1, wherein, The temperature control mechanism comprises a temperature sensor, a heat-rising element and a heat sink, the temperature sensor is connected to the heat-conducting plate and is used to detect the real-time temperature of the heat-conducting plate, the heat-rising element and the heat sink are both arranged on the base and are both connected to the heat-conducting plate, the heat-rising element is used to heat or cool the heat-conducting plate, and the heat sink is used to cool the heat-conducting plate.
6. The temperature control device of claim 1, wherein, The vacuumizing mechanism comprises a vacuum pump, a three-way pipe and an air pressure sensor, the first end of the three-way pipe is connected to the air exhaust hole, the second end of the three-way pipe is connected to the vacuum pump, the third end of the three-way pipe is connected to the air pressure sensor, the vacuum pump is used to exhaust air outward, and the air pressure sensor is used to detect the real-time vacuum degree.
7. The temperature control device of claim 1, wherein, The temperature control device further comprises a positioning mechanism, the positioning mechanism comprises a positioning frame and a positioning piece, the positioning frame is arranged on the base and simultaneously surrounds the heat-conducting plate and the disc body, the disc body is provided with a limiting groove, and the positioning piece is movably arranged in the positioning frame and is matched with the limiting groove.
8. The temperature control device of claim 1, wherein, The positioning piece comprises an elastic piece and a ball, the positioning frame is provided with a positioning groove, one end of the elastic piece is connected to the bottom wall of the positioning groove, the other end is connected to the ball, and the ball is slidably arranged in the positioning groove.
9. The temperature control device of claim 8, wherein, The limiting groove is conical, the midpoint of the limiting groove is higher than the center of the ball, the ball extends into the limiting groove and abuts against the side wall of the limiting groove. The temperature control device comprises any one of claims 1-9.
10. A droplet digital PCR instrument, characterized by,