A nucleic acid amplification device and a nucleic acid amplification system

Abstract

The present application relates to a nucleic acid amplification device and a nucleic acid amplification system, the nucleic acid amplification device comprising: a carrier capable of carrying and heating a reaction sample; a carrying portion for carrying the carrier.A nucleic acid detection system comprising the nucleic acid amplification device and a detection module for detecting the reaction sample.The carrying portion carries the carrier, the carrier can carry the reaction sample and also heat the reaction sample, the carrier is a whole structure, there is no gap and air interface between the reaction sample and the carrier, therefore, the heat conduction efficiency between the carrier and the reaction sample is improved, and the heating efficiency and the detection efficiency are improved.

Description

Technical Field

[0001] This invention relates to the field of medical technology, and in particular to a nucleic acid amplification device and a nucleic acid amplification system. Background Technology

[0002] PCR (polymerase chain reaction) is a molecular biology experimental method for the in vitro enzymatic synthesis of specific DNA fragments. PCR amplification, i.e. nucleic acid amplification, mainly consists of repeated thermal cycles of three steps: high-temperature denaturation, low-temperature annealing, and appropriate-temperature extension.

[0003] In existing technologies, nucleic acid amplification systems for nucleic acid detection include a heater and a sample holding structure that can be placed on the heater. The sample holding structure is often a shell or tube. The heater heats the sample holding structure, thereby heating the sample inside. However, the air interface between the heated sample holding structure and the heater results in low thermal conductivity, leading to low heating and detection efficiency. The large thickness of the reaction sample inside the shell or tube also results in a long time required for homogenization, causing slow heating and cooling rates. The complex heater structure hinders heat transfer between the heater and the reaction sample, further contributing to slow heating and cooling rates.

[0004] In addition, in order to facilitate the control of the heater, it is necessary to detect the temperature of the reaction sample. However, the temperature detection methods commonly used in the prior art have low accuracy, resulting in inaccurate detection results.

[0005] In addition, existing PCR instruments have slow heating and cooling rates of the reaction solution during the PCR amplification process, which seriously affects the detection rate. Summary of the Invention

[0006] One object of the present invention is to provide a nucleic acid amplification device to at least solve one of the above-mentioned problems.

[0007] To achieve the above objectives, a first aspect of the present invention provides a nucleic acid amplification apparatus, comprising:

[0008] A carrier capable of holding and heating the reaction sample;

[0009] The support portion is used to support the carrier.

[0010] Optionally, it also includes a housing, to which the support unit is movably connected to switch between a placement position and a testing position.

[0011] Optionally, the nucleic acid amplification device further includes a cooling mechanism for cooling the support portion.

[0012] Optionally, when the support portion is located at the detection position, the cooling mechanism is in communication with the support portion.

[0013] Optionally, the support portion is slidably connected to the housing.

[0014] Optionally, the support portion includes:

[0015] The supporting body is capable of supporting and cooling the carrier;

[0016] A fixing mechanism that enables the carrier to be tightly attached to the supporting body;

[0017] A support base that supports the load-bearing body and the fixing mechanism.

[0018] Optionally, the fixing mechanism includes:

[0019] A fixing component, the fixing component being connected to the support base;

[0020] A clamping part is connected to the fixing component and can switch between a clamping state and a clearance state.

[0021] Optionally, the clamping part is rotatably connected to the fixing component, and the fixing mechanism further includes a switching structure, through which the clamping part switches between the clamping state and the avoidance state.

[0022] Optionally, the conversion structure includes a first slide groove and a second slide groove formed on the fixing component, a hook connected to the fixing component and a protrusion connected to one end of the pressing part, the other end of the pressing part being slidably and rotatably connected to the first slide groove, the protrusion being able to slide in the second slide groove and be able to engage with and disengage from the second slide groove.

[0023] Optionally, the carrier is formed with a containment cavity for accommodating the reaction sample, and the carrier includes a heater.

[0024] Optionally, the heater includes a heat spreader layer that contacts the reaction sample within the containment cavity.

[0025] Optionally, the heater further includes a heating element and a temperature calibration unit for responding to the temperature of the heating element.

[0026] Optionally, the carrier further includes a first temperature detection unit, which measures the temperature at the temperature calibration unit; or,

[0027] The carrier includes a second temperature detection unit connected to the temperature calibration unit and used to measure the temperature at the temperature calibration unit.

[0028] Optionally, the supporting body is provided with a clearance portion, which is used to avoid the first temperature detection unit or the second temperature detection unit, as well as the temperature calibration unit.

[0029] Optionally, the first temperature detection unit is a contact temperature sensor or a non-contact temperature sensor.

[0030] Optionally, when the first temperature detection unit is a contact temperature sensor, the first temperature detection unit and the temperature calibration unit are in elastic contact.

[0031] Optionally, the fixing mechanism has a first through hole, and the carrier is at least partially located in the first through hole.

[0032] Optionally, the wall of the first through hole is provided with a positioning element for positioning the carrier.

[0033] Optionally, the upper surface of the fixing mechanism is further provided with a pick-and-place groove that communicates with the first through hole.

[0034] Optionally, the supporting body is at least partially inserted through the first through hole.

[0035] Optionally, the carrier portion further includes an electrical contact, which is at least partially located in the first through hole to make electrical contact with the carrier.

[0036] Optionally, the electrical contact includes:

[0037] Power supply contacts, and / or

[0038] Current detection contacts and voltage detection contacts.

[0039] Optionally, the carrier includes a cooling body and a cold head connected to the cooling body, the carrier being able to fit tightly against the cold head, and the cooling body being used for the flow of cooling medium.

[0040] Optionally, the carrier has a flat structure.

[0041] Optionally, the number of the support parts is one or at least two. When the number of the support parts is at least two, at least two of the support parts can be connected to the cooling mechanism respectively.

[0042] Optionally, the support portion further includes a drive mechanism for driving the support base closer to or away from the carrier.

[0043] Optionally, the nucleic acid amplification device further includes a guiding component connected between the support portion and the housing, and used to guide the support portion.

[0044] Optionally, the support portion includes a pipe joint, and the cooling mechanism is connected to the support portion through the pipe joint.

[0045] Optionally, the carrier portion further includes a PCB board, which is connected to the electrical contacts.

[0046] Optionally, the cooling mechanism is located outside the housing.

[0047] Another object of the present invention is to provide a nucleic acid amplification control method to at least solve one of the above-mentioned problems.

[0048] To achieve this objective, the second aspect of the present invention adopts the following technical solution:

[0049] A nucleic acid detection system includes the nucleic acid amplification device and a detection module, wherein the detection module is used to detect the reaction sample.

[0050] Optionally, a communication module is also included, and both the nucleic acid amplification device and the detection module are connected to the communication module.

[0051] Optionally, an output device may also be included, which is connected to the detection module.

[0052] As can be seen from the above, the technical solution provided by this invention features a carrier that supports the reaction sample. This carrier can both hold and heat the reaction sample. The carrier has an integral structure, with no gaps or air interfaces between the reaction sample and the carrier. Therefore, the thermal conductivity between the carrier and the reaction sample is improved, thereby increasing both heating and detection efficiency. The nucleic acid amplification device provided by this invention can achieve rapid heating and cooling of the reaction sample, shortening the detection time. Attached Figure Description

[0053] Figure 1 This is a schematic diagram of the nucleic acid amplification system provided in an embodiment of the present invention;

[0054] Figure 2 This is a schematic diagram of the nucleic acid amplification system (cooling mechanism removed) provided in an embodiment of the present invention;

[0055] Figure 3 This is a cross-sectional view of the nucleic acid amplification system provided in an embodiment of the present invention;

[0056] Figure 4a This is a schematic diagram of the structure of a partial nucleic acid amplification system provided in an embodiment of the present invention;

[0057] Figure 4b This is a schematic diagram of the structure of a partial nucleic acid amplification device provided in an embodiment of the present invention;

[0058] Figure 4cThis is an exploded view of the carrier provided in the embodiments of the present invention;

[0059] Figure 4d This is an exploded view of the carrier provided in an embodiment of the present invention from another perspective;

[0060] Figure 5 This is a schematic diagram of the structure of the supporting body provided in an embodiment of the present invention;

[0061] Figure 6 This is a schematic diagram of the structure of the support portion provided in an embodiment of the present invention;

[0062] Figure 7 yes Figure 6 A magnified view of a section at point A in the middle;

[0063] Figure 8 This is a schematic diagram of the structure of the bearing portion removing the clamping portion provided in an embodiment of the present invention;

[0064] Figure 9 This is a schematic diagram of another structure provided by an embodiment of the present invention, showing the removal of the clamping part from the bearing part;

[0065] Figure 10a This is a schematic diagram of the carrier provided in an embodiment of the present invention;

[0066] Figure 10b This is a schematic diagram of the carrier provided in an embodiment of the present invention from another perspective;

[0067] Figure 11 This is a cross-sectional view of a portion of the nucleic acid amplification apparatus provided in an embodiment of the present invention;

[0068] Figure 12 This is the temperature curve of the reaction sample provided in the embodiments of the present invention.

[0069] In the picture:

[0070] 1. Carrier; 11. Receiving cavity; 12. Heater; 121. Heat spreader layer; 122. Heating element; 123. Electrical contact part; 124. Temperature calibration part; 125. External electrical connection contact point; 126. Electrical connection lead; 13. Second temperature detection unit;

[0071] 2. Load-bearing component;

[0072] 21. Load-bearing body; 211. Mounting plate; 212. Cooling body; 2121. Fins; 2122. Channel; 213. Cold head; 2131. Clearance section;

[0073] 22. Fixed mechanism;

[0074] 221. Fixing component; 2211. First through hole; 2212. Pick-up and drop-out slot; 2213. Positioning component; 2214. Fixing plate; 2215. Fixing strip;

[0075] 222, clamping part; 2221, light-transmitting hole;

[0076] 23. Support base; 231. Cooling tank; 232. Base;

[0077] 24. Conversion structure; 241. First slide groove; 242. Hook; 243. Protrusion; 244. Second slide groove;

[0078] 25. Contact temperature sensor; 26. Non-contact temperature sensor; 27. Electrical contact; 29. ​​Pipe fitting; 20. PCB board;

[0079] 3. Detection module;

[0080] 4. Housing;

[0081] 5. Guide assembly; 51. Slide rail; 52. Slider;

[0082] 6. Cooling mechanism; 61. Male connector. Detailed Implementation

[0083] The technical solution of the present invention will be further described below with reference to the accompanying drawings and specific embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and not intended to limit it. Furthermore, it should be noted that, for ease of description, only the parts relevant to the present invention are shown in the accompanying drawings, not all of them.

[0084] This invention defines certain directional terms. Unless otherwise stated, the directional terms used, such as "up," "down," "left," "right," "inner," and "outer," are used for ease of understanding and therefore do not constitute a limitation on the scope of protection of this invention.

[0085] In this invention, unless otherwise explicitly specified and limited, "above" or "below" the second feature can include direct contact between the first and second features, or contact between the first and second features through another feature between them. Furthermore, "above," "over," and "on top" of the second feature includes the first feature being directly above or diagonally above the second feature, or simply indicates that the first feature is at a higher horizontal level than the second feature. "Below," "below," and "under" the second feature includes the first feature being directly below or diagonally below the second feature, or simply indicates that the first feature is at a lower horizontal level than the second feature.

[0086] In the description of this invention, unless otherwise explicitly specified and limited, the terms "connected," "linked," and "fixed" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral part; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; they can refer to the internal communication of two components or the interaction between two components. Those skilled in the art can understand the specific meaning of the above terms in this invention based on the specific circumstances.

[0087] This embodiment provides a nucleic acid amplification device that can be used in PCR amplification and nucleic acid detection.

[0088] like Figures 1-10a As shown, the nucleic acid amplification device provided in this embodiment includes a carrier 1 and a support part 2. The carrier 1 can carry and heat the reaction sample, and the support part 2 is used to carry the carrier 1.

[0089] The carrier 2 carries the carrier 1. The carrier 1 can carry the reaction sample and heat the reaction sample at the same time. The carrier 1 has an integral structure. There are no gaps or air interfaces between the reaction sample and the carrier 1. Therefore, the thermal conductivity between the carrier 1 and the reaction sample is improved, thereby improving the heating efficiency and detection efficiency.

[0090] like Figure 2 As shown, the nucleic acid amplification system may also include a housing 4, with a carrier 2 movably connected to the housing 4 to switch between a sample placement position and a detection position. When the carrier 2 is in the sample placement position, a carrier 1 containing the reaction sample can be placed in the carrier 2; when the carrier 2 is in the detection position, the reaction sample can be detected.

[0091] Optionally, the support part 2 is slidably connected to the housing 4 so that the support part 2 can stably switch between the sampling position and the detection position.

[0092] like Figure 3 and Figure 4a As shown, to facilitate the sliding of the support part 2, the nucleic acid amplification device may optionally include a guide component 5, which is connected between the support part 2 and the housing 4 and is used to guide the support part 2.

[0093] Specifically, the guide assembly 5 includes a slide rail 51 and a slider 52. The slide rail 51 is connected to the support portion 2, and the slider 52 is connected to the housing 4. The slider 52 is slidably connected to the slide rail 51. Of course, in other optional embodiments, the slider 52 may be connected to the support portion 2, and the slide rail 51 may be connected to the housing 4.

[0094] like Figure 1As shown, optionally, the nucleic acid amplification device further includes a cooling mechanism 6, which is used to cool the carrier portion 2. The cooling mechanism 6 cools the carrier portion 2, and the carrier 1 is placed on the carrier portion 2. Therefore, the carrier portion 2 can cool the carrier 1, thereby cooling the reaction sample inside the carrier 1. The carrier 1 can also heat the reaction sample inside it. Therefore, the reaction sample can be heated, cooled, and kept at a constant temperature within the carrier 1, thereby achieving amplification.

[0095] Optionally, when the carrier 2 is in the detection position, the cooling mechanism 6 is connected to the carrier 2. When the carrier 2 moves within the housing 4 and leaves the detection position, the carrier 2 is not connected to the cooling mechanism 6, thus simplifying the piping between the cooling mechanism 6 and the carrier 2. Optionally, the cooling mechanism 6 is located outside the housing 4.

[0096] like Figure 3 and Figure 4a As shown, the support unit 2 includes a pipe connector 29, and the cooling mechanism 6 communicates with the support unit 2 through the pipe connector 29. The pipe connector 29 can be a female connector, and the cooling mechanism 6 can include a male connector 61. The male connector 61 can pass through the housing 4, and the female connector and the male connector 61 can be inserted into each other. When the support unit 2 moves to the detection position, the male connector 61 and the female connector are inserted into each other. When the support unit 2 moves away from the detection position, the male connector 61 and the female connector gradually separate.

[0097] like Figure 4b As shown, it can be understood that there are two pipe connectors 29 and two male connectors 61. One pipe connector 29 can be connected to one male connector 61, and the other pipe connector 29 can be connected to another male connector 61, thereby realizing the injection and return of cooling medium.

[0098] like Figure 4a , Figures 4c-6 As shown, the support unit 2 includes a support body 21, a fixing mechanism 22, and a support base 23. The support body 21 can support and cool the carrier 1. The fixing mechanism 22 can keep the carrier 1 close to the support body 21 to avoid gaps between the carrier 1 and the support body 21, thereby improving the heat transfer efficiency between the carrier 1 and the support body 21. The support base 23 can support the support body 21 and the fixing mechanism 22. Optionally, the support unit 2 may also include a base 232, which is connected to the lower side of the support base 23, and a slide rail 51 is connected to the lower side of the base 232.

[0099] Optionally, a cooling groove 231 with an opening facing the supporting body 21 can be formed on the support base 23, and part of the supporting body 21 is disposed in the cooling groove 231. A pipe joint 29 passes through the side wall of the support base 23 and communicates with the cooling groove 231 to introduce the cooling medium into the cooling groove 231 and directly cool the supporting body 21 located in the cooling groove 231.

[0100] like Figure 5 As shown, when the carrier 1 is cooled by a circulating cooling medium within the carrier body 21, the carrier body 21 may include a cooling body 212 and a cold head 213 connected to the cooling body 212, and the carrier 1 can be tightly attached to the cold head 213. Further, the carrier 1 is placed on the upper surface of the cold head 213. The cooling body 212 is used for circulating the cooling medium. The cooling medium cools the cooling body 212, the cooling body 212 cools the cold head 213, and thus cools the carrier 1 placed on the cold head 213.

[0101] In one specific embodiment, the cooling body 212 includes a plurality of parallel fins 2121, and channels 2122 for the flow of cooling medium are formed between the fins 2121. The fins 2121 can increase the contact area between the cooling medium and the supporting body 21, thereby accelerating the cooling of the cold supporting body 21.

[0102] Preferably, a mounting plate 211 is also provided between the cooling body 212 and the cold head 213. The mounting plate 211 covers the opening of the cooling tank 231 to prevent the cooling medium from flowing out.

[0103] like Figure 4c , Figure 4d and Figure 6 As shown, the fixing mechanism 22 includes a fixing component 221 and a pressing part 222. The fixing component 221 is connected to the support base 23 or the base 232. The pressing part 222 is connected to the fixing component 221 and can switch between a pressing state and a clearance state. When the pressing part 222 is in the pressing state, it can press the carrier 1 onto the cold head 213; when the pressing part 222 is in the clearance state, the carrier 1 can be placed on the cold head 213 or removed from the cold head 213.

[0104] like Figure 4c , Figure 4d and Figure 6 As shown, preferably, the pressing part 222 is plate-shaped, so that all parts of the pressing part 222 press the carrier 1, thereby making all parts of the carrier 1 adhere tightly to the bearing part 2. The pressing part 222 is also provided with a light-transmitting hole 2221, through which fluorescence is detected.

[0105] The clamping part 222 is rotatably connected to the fixing component 221. The fixing mechanism 22 also includes a switching structure 24, through which the clamping part 222 switches between a clamping state and a clearance state. When the clamping part 222 rotates to contact the carrier 1, the clamping part 222 can clamp the carrier 1 through the switching structure 24 and switch to the clearance state through the switching structure 24.

[0106] like Figure 4c , Figure 4d and Figures 6-8As shown, the clamping structure conversion structure 24 includes a first slide groove 241 and a second slide groove 244 formed on the fixing component 221, a hook 242 connected to the fixing component 221, and a latching protrusion 243 connected to one end of the clamping part 222. The other end of the clamping part 222 is slidably and rotatably connected to the first slide groove 241. The latching protrusion 243 can slide in the second slide groove 244, and the latching protrusion 243 can engage with and disengage from the hook 242 in the second slide groove 244. The clamping part 222 is slidably and rotatably connected to the first slide groove 241.

[0107] When the clamping part 222 is in the clamping state, the latch 243 engages with the latch 242, and the clamping part 222 can remain in the clamping state. When the clamping part 222 switches from the clamping state to the clearance state, firstly, the clamping part 222 is pushed along the first direction within the first slide groove 241 and the second slide groove 244, causing the latch 242 to disengage from the latch 243. Then, one end of the clamping part 222 can be lifted, causing the latch 243 to disengage from the second slide groove 244. At the same time, the other end of the clamping part 222 rotates within the first slide groove 241 until the clamping part 222 rotates to the clearance position. It can be understood that the clamping part 222 in the clearance state is not located in a specific position, as long as the carrier 1 can be placed or removed.

[0108] Preferably, the hook 242 is located at one end of the second slide groove 244, and the protrusion 243 can disengage from the second slide groove 244 as the clamping part 222 rotates when it slides to the other end of the second slide groove 244. One end of the clamping part 222 can be connected to a rotating shaft, which is slidably and rotatably disposed in the first slide groove 241.

[0109] Optionally, a conversion structure 24 is provided on both sides of the fixing component 221 along the second direction, so that the pressing part 222 is stably positioned in the pressing state. The second direction is perpendicular to the first direction, and both the first and second directions are parallel to the surface of the carrier 1 placed on the cold head 213.

[0110] Optionally, the fixing component 221 includes a fixing plate 2214 and a fixing strip 2215 connected to the fixing plate 2214. The first groove 241 and the second groove 244 are both formed on the fixing strip 2215. There can be two fixing strips 2215, which are spaced apart along the second direction, and the pressing part 222 is disposed between the two fixing strips 2215.

[0111] The fixing mechanism 22 has a first through hole 2211, and the carrier 1 is at least partially located in the first through hole 2211. Preferably, a portion of the carrier 1 in the thickness direction is disposed on the first through hole 2211 so that the plate-shaped pressing part 222 can contact the carrier 1 and thereby press the carrier 1. Of course, in other embodiments, the carrier 1 can also be completely placed in the first through hole 2211, and a protrusion can be provided on the pressing part 222, which contacts the surface of the carrier 1 to press the carrier 1.

[0112] Optionally, the support body 21 may also be at least partially inserted through the first through hole 2211. Of course, in other optional embodiments, the support body 21 may also be located below the fixing mechanism 22, with the carrier 1 passing through the first through hole 2211 and connected to the support body 21. Optionally, the cold head 213 may be at least partially located in the first through hole 2211.

[0113] In this embodiment, the first through hole 2211 is formed on the fixing component 221, and further, the first through hole 2211 is formed on the fixing plate 2214.

[0114] like Figure 8 As shown, a positioning element 2213 for positioning the carrier 1 is provided on the wall of the first through hole 2211. Multiple positioning elements 2213 can be provided, spaced apart circumferentially along the first through hole 2211. The positioning element 2213 can be a protrusion connected to the wall of the first through hole 2211. The positioning element 2213 positions the carrier 1, ensuring accurate alignment with the cold head 213. The positioning element 2213 also reduces the contact area between the carrier 1 and the fixing plate 2214, thereby reducing heat exchange between the fixing plate 2214 and the carrier 1, and ensuring high temperature uniformity of the carrier 1.

[0115] The upper surface of the fixing mechanism 22 is also provided with a pick-and-place groove 2212 communicating with the first through hole 2211. The pick-and-place groove 2212 facilitates the operator or automated equipment to contact the side of the carrier 1, thereby clamping the side of the carrier 1 and making it convenient to pick up and place the carrier 1. Optionally, pick-and-place grooves 2212 are provided on both sides of the through hole along the second direction.

[0116] In this embodiment, the number of support parts 2 is one. Of course, in other optional embodiments, the number of support parts 2 can be at least two. When the number of support parts 2 is at least two, at least two support parts 2 can be connected to the cooling mechanism 6 respectively, for example... Figure 1 As shown, four support sections 2 are provided.

[0117] In this embodiment, the cooling mechanism 6 is in continuous contact with the carrier 1. Of course, in other optional embodiments, the carrier 2 also includes a driving mechanism, which is used to drive the support 23 to move closer to or away from the carrier 1 so that the cooling mechanism 6 is in intermittent contact with the carrier 1.

[0118] When the reaction sample is in the heating stage, the cooling mechanism 6 may not be in contact with the carrier 1. When the reaction sample is in the cooling stage, the cooling mechanism 6 is in contact with the carrier 1. When the reaction sample is in the temperature holding stage, the cooling mechanism 6 may intermittently contact the carrier 1 to maintain the temperature balance of the carrier 1, or the cooling mechanism 6 may not continuously contact the carrier 1, and the temperature of the reaction sample may be controlled by the heating function of the carrier 1.

[0119] like Figure 10a As shown, the carrier 1 has a receiving cavity 11 for accommodating the reaction sample, and the carrier 1 includes a heater 12. The carrier 1 has an integral structure, and there is no gap or air interface between the reaction sample and the heater 12. Therefore, the heat transfer rate between the carrier 1 and the reaction sample is increased, thereby accelerating the nucleic acid amplification process and improving the detection efficiency.

[0120] Optionally, the carrier 1 has a flat structure. Furthermore, the receiving cavity 11 can also be a flat structure. It is understood that a flat structure means that the thickness dimension of the receiving cavity 11 is much smaller than its width or length dimension. For example, the receiving cavity 11 can be a cuboid, with a length-to-thickness ratio greater than 5:1, such as 90:1. The thickness dimension of the receiving cavity 11 can be 0.3-1.0 mm, and the width and length of the receiving cavity 11 are approximately 10 mm and 20 mm, respectively. The thickness dimension refers to the arrangement direction of the heating element 122 and the receiving cavity 11. For example, the receiving cavity 11 can also be a cylindrical structure with a diameter-to-thickness ratio greater than 5:1, such as a thickness of 0.3-1.0 mm and a diameter of 5-20 mm. Of course, the cross-section of the receiving cavity 11 can be polygonal or elliptical, etc.

[0121] Specifically, the heater 12 is in direct contact with the reaction sample inside the containment cavity 11. There are no other conductive interfaces between the reaction sample and the heater 12, thereby reducing the conductive interface between the heater 12 and the containment cavity 11 and further improving the conduction efficiency. At the same time, the absence of an interface between the heater 12 and the reaction sample results in lower thermal resistance, enabling faster temperature control while achieving rapid heat conduction.

[0122] The heater 12 includes a heat spreader 121, which is in contact with the reaction sample inside the receiving cavity 11. The heat spreader 121 ensures uniform heat conduction in both the longitudinal and transverse directions (i.e., the thickness direction of the reaction sample and the surface perpendicular to the thickness direction), thus ensuring the temperature uniformity of the sample liquid. Optionally, the heat spreader 121 is made of a conductive or insulating material, such as aluminum, copper, or other conductive materials, or highly thermally conductive ceramics or other insulating materials.

[0123] like Figures 9-11 As shown, optionally, the carrier portion 2 further includes an electrical contact 27, which is at least partially located in the first through hole 2211 for electrical contact with the carrier 1. Optionally, the electrical contact 27 is disposed close to the wall of the first through hole 2211. This arrangement of the electrical contact 27 can improve the structural compactness of the carrier portion 2. Optionally, the heater 12 further includes a heating element 122 and an electrical contact portion 123 electrically connected to the heating element 122, with the electrical contact 27 electrically connected to the electrical contact portion 123. The heating element 122 can be a resistance wire, etc.

[0124] The carrier 2 may also include a PCB board 20, which is connected to the electrical contact 27, thereby supplying power to the electrical contact 27 and transmitting current and voltage signals through the PCB board 20.

[0125] In this embodiment, the heating element 122 is temperature-measured using a resistance thermometer, and power is supplied to the heating element 122 via electrical contacts 27 to generate heat. Optionally, the electrical contacts 27 include a power supply contact, a current detection contact, and a voltage detection contact. The power supply contact supplies power to the heating element 122, while the current detection contact and voltage detection contact detect the current I and voltage U of the heating element 122, respectively. The resistance R of the heating element 122 at temperature T can then be obtained using R = U / I. According to the formula R = R0(1 + α... T T = T - T0, where R is the resistance value of heating element 122 at temperature T, T0 is the nominal temperature, and R0 is the resistance value at the nominal temperature (the resistance value at the nominal temperature is simply called the nominal resistance value; it can be understood that the nominal resistance refers to the actual resistance value claimed (or marked) at this temperature, where this temperature is the nominal temperature, which can be arbitrarily selected according to requirements; α is the temperature coefficient of resistance of the material). The temperature of heating element 122 at resistance R can be obtained. The temperatures of heating element 122, heat spreader 121, and reaction sample are basically the same; therefore, the temperature of the reaction sample can be obtained.

[0126] Of course, in other alternative embodiments, electrical contact 27 may include a power supply contact, or may include only a current detection contact and a voltage detection contact.

[0127] The resistance of the heating element 122 and its temperature have a specific relationship as shown in the formula above. Therefore, while heating, the real-time resistance change of the heating element 122 of the carrier 1 is measured, and the average temperature of the heating element 122 is derived by comparing the resistance temperature coefficient with the resistance value at the nominal temperature (referred to as the nominal resistance value). By monitoring the resistance value of the heating element 122 to calculate the temperature, compared to measuring the temperature of the heating element 122 using a temperature sensor, this method provides a real-time, time-free representation of the current temperature of the carrier 1, which can be used for rapid feedback control of the carrier 1 and the temperature of the reaction sample. The disadvantage of this method is that for resistors of the same type, such as copper wire resistors, the nominal resistance value and resistance temperature coefficient may differ slightly between resistors. This can lead to slight differences in the resistance temperature coefficient and nominal resistance value between individual heating elements 122, potentially causing temperature measurement errors.

[0128] To avoid the aforementioned errors, the heater 12 may optionally include a temperature calibration unit 124 for reflecting the temperature of the heating element 122. Since the temperature calibration unit 124 can reflect the temperature of the heating element 122, its temperature can be detected by other means, thereby calibrating the temperature coefficient of resistance and the nominal resistance value, and thus detecting the accurate temperature of the heating element 122 by resistance thermometry. Optionally, the temperature calibration unit 124 is disposed at the bottom of the carrier 1.

[0129] To detect the temperature of the heating element 122, the carrier portion 2 may optionally include a temperature detection unit for detecting the temperature of the temperature calibration portion 124. The temperature detection unit may be a first temperature detection unit, used to measure the temperature at the temperature calibration portion 124. The first temperature detection unit may be electrically connected to the PCB board 20. The first temperature detection unit can be reused, thereby saving costs. Specifically, as... Figure 8 As shown, the first temperature detection unit is a non-contact temperature sensor 26, such as an infrared sensor. The first temperature detection unit can also be a contact temperature sensor 25, which detects temperature by contacting the temperature calibration unit 124.

[0130] When the first temperature detection unit is a contact temperature sensor 25, the first temperature detection unit and the temperature calibration unit 124 are in elastic contact to ensure complete contact between the first temperature detection unit and the temperature calibration unit 124. For example, the contact temperature sensor 25 is electrically connected to the PCB board 20 through an elastic element such as a spring.

[0131] Of course, in other alternative embodiments, the first temperature detection unit may not be included. Instead, the carrier 1 includes a second temperature detection unit 13 connected to the temperature calibration unit 124 and used to measure the temperature at the temperature calibration unit 124. The second temperature detection unit 13 may be discarded as a consumable along with the carrier 1.

[0132] like Figure 10b As shown, when the second temperature detection unit 13 is connected to the carrier 1, the nucleic acid amplification device may optionally include external electrical contact points 125 and electrical connection leads 126. The number of external electrical contact points 125 and electrical connection leads 126 may both be two. The number of two temperature calibration units 124 is two, and the two temperature calibration units 124 are insulated from each other. The two external electrical contact points 125 are located on opposite sides of the two temperature calibration units 124. One external contact point is electrically connected to one temperature calibration unit 124 via an electrical connection lead 126, and the other external contact point is electrically connected to the other temperature calibration unit 124 via another electrical connection lead 126.

[0133] The temperature calibration unit 124 is electrically connected to the outside via an external electrical connection contact 125 through an electrical connection lead 126. The diameter of the electrical connection lead 126 is smaller than that of the temperature calibration unit 124 and the external electrical connection contact 125, thereby reducing the heat loss of the temperature calibration unit 124 through the electrical connection lead 126. The temperature calibration unit 124 can reflect the temperature of the heating element 122. The second temperature detection unit 13 achieves good electrical and thermal contact with the temperature calibration unit 124 through a solder joint. When the temperature of the heating element 122 changes, the second temperature detection unit 13 can quickly and accurately sense the temperature change. The temperature change causes a change in the resistance of the second temperature detection unit 13. By detecting the change in the resistance of the second temperature detection unit 13 in real time at the external electrical connection contact 125, temperature detection can be achieved.

[0134] In existing technologies, temperature sensors or other temperature detection units are used to detect the temperature of the reaction sample. However, since it takes time for heat to transfer from the reaction sample to the temperature detection unit, the measurement result under normal circumstances will have a temperature measurement delay of 1-2 seconds. During rapid heating and cooling, the temperature change of the reaction sample can reach more than 30°C within 1-2 seconds. Therefore, controlling the carrier 1 through the temperature detection unit is relatively difficult during rapid heating and cooling. In this embodiment, the temperature detected by the resistance thermometry method is calibrated using a first temperature detection unit or a second temperature detection unit 13. Specifically, the nominal resistance value and the temperature coefficient of resistance are calibrated. When calibrating using the first temperature detection unit or the second temperature detection unit 13, a certain temperature can be maintained for 1-2 seconds to make the temperature of the temperature detection unit consistent with the temperature of the reaction sample, so as to obtain the accurate temperature under the resistance R, and then calibrate the nominal resistance value and the temperature coefficient of resistance.

[0135] To more clearly illustrate the correction process for the resistance temperature measurement method, combined with... Figure 12The diagram illustrates the calibration process of resistance thermometry using a temperature detection unit in a practical test. Before calibrating the temperature value, an initial RT temperature curve, i.e., a preset temperature curve, is established. Then, a very small current (e.g., less than 1 mA) is applied to the heating element 122 of the carrier 1. The purpose of applying a very small current is to read the resistance of the heating element 122 without causing it to overheat.

[0136] First calibration: The temperature detection unit measures the first temperature calibration value T1, and the resistance detection unit detects the first voltage U1 and the first current I1 of the heating element 122 at temperature T1. According to R=U / I, the resistance R1 of the heating element 122 at temperature T1 can be obtained.

[0137] Second calibration: Subsequently, the temperature detection unit measures the second temperature calibration value T2, and the resistance detection unit detects the second voltage U2 and the second current I2 of the heating element 122 at temperature T2. According to R=U / I, the resistance R2 of the heating element 122 at temperature T2 can be obtained.

[0138] Finally, based on the two sets of linear equations in two variables: R1=R0(1+α) T1) and R2=R0(1+α) By obtaining the specific values ​​of R0 and α (T2), the accurate RT curve is obtained. Subsequently, the temperature of the heating element 122 measured by the resistance thermometer can be used as feedback for accurate temperature control.

[0139] Continue to refer to Figure 12 When obtaining the first temperature calibration value, this temperature calibration value can be considered as the nominal resistance value. Therefore, based on this temperature calibration value, the formula R=R0(1+α) can be applied. The R0 in T) is corrected once to achieve the first calibration of the temperature value measured by the resistance thermometry method (e.g., Figure 12 The temperature curve measured by the resistance thermometry method in the figure experienced a fluctuation after the first calibration.

[0140] Temperature calibration values ​​can be detected throughout the entire nucleic acid amplification process, allowing for multiple temperature calibrations in subsequent processes to further improve detection accuracy.

[0141] This embodiment does not rely entirely on the temperature value measured by the uncalibrated resistance thermometry method, nor does it rely entirely on the temperature control carrier 1 detected by the temperature detection unit. Instead, it overcomes the above-mentioned defects by combining the two to calibrate the temperature of the carrier 1, thereby enabling rapid and accurate control of the temperature of the carrier 1 and achieving the purpose of accurate temperature control.

[0142] like Figure 11As shown, the supporting body 21 has a clearance portion 2131, which is used to avoid the first temperature detection unit or the second temperature detection unit 13, and to avoid the temperature calibration unit 124. The clearance portion 2131 can be a slot or hole provided on the cooling mechanism 6, such as... Figure 5 As shown, furthermore, a clearance portion 2131 is provided on the cold head 213. The clearance portion 2131 can prevent the cooling mechanism 6 from affecting the temperature of the temperature calibration section 124, ensuring that the temperature calibration section 124 accurately reflects the temperature of the heating element 122.

[0143] refer to Figure 3 This embodiment also provides a nucleic acid detection system, which includes the aforementioned nucleic acid amplification device and a detection module 3. The detection module 3 is used to detect reaction samples. The detection module 3 can be a fluorescence detection unit, etc.

[0144] The nucleic acid detection system also includes a communication module. The nucleic acid amplification device and the detection module 3 are both connected to the communication module, thereby controlling the detection module 3, the heating element 122 of the carrier 1, and the cooling mechanism 6.

[0145] The nucleic acid testing system also includes output devices such as computers, which are connected to the testing module 3 to output relevant data.

[0146] Although the present invention has been described in detail above with general descriptions, specific embodiments, and experiments, modifications or improvements can be made to it, which will be obvious to those skilled in the art. Therefore, all such modifications or improvements made without departing from the spirit of the present invention fall within the scope of protection claimed by the present invention.

Claims

1. A nucleic acid amplification device, characterized in that, include: The carrier (1) is capable of supporting and heating the reaction sample; The support part (2) is used to support the carrier (1); The supporting part (2) includes: The supporting body (21) is capable of supporting and cooling the carrier (1); The fixing mechanism (22) enables the carrier (1) to be attached to the bearing body (21), and the fixing mechanism (22) is provided with a first through hole (2211). Support base (23), which can support the bearing body (21) and the fixing mechanism (22); The carrier (1) has a cavity (11) for accommodating the reaction sample. The carrier (1) includes a heater (12). The heater (12) includes a heat spreader (121). The heat spreader (121) is in contact with the reaction sample in the cavity (11). The heater (12) also includes a heating element (122) and a temperature calibration unit (124) for reacting the temperature of the heating element (122). The carrier (2) also includes a temperature detection unit for measuring the temperature of the temperature calibration unit (124). The carrier (2) further includes an electrical contact (27), which is at least partially located in the first through hole (2211) to make electrical contact with the carrier (1). The electrical contact (27) includes: Power supply contacts, and / or Current detection contacts and voltage detection contacts.

2. The nucleic acid amplification device according to claim 1, characterized in that, It also includes a housing (4), to which the support part (2) is movably connected to the housing (4) to switch between the sampling position and the detection position.

3. The nucleic acid amplification device according to claim 2, characterized in that, The nucleic acid amplification device also includes a cooling mechanism (6) for cooling the support unit (2).

4. The nucleic acid amplification device according to claim 3, characterized in that, When the support part (2) is located at the detection position, the cooling mechanism (6) is connected to the support part (2).

5. The nucleic acid amplification device according to claim 2, characterized in that, The support part (2) is slidably connected to the housing (4).

6. The nucleic acid amplification device according to claim 1, characterized in that, The fixing mechanism (22) includes: Fixing component (221), which is connected to the support base (23); A clamping part (222) is connected to the fixing component (221) and can switch between a clamping state and a clearance state.

7. The nucleic acid amplification device according to claim 6, characterized in that, The clamping part (222) is rotatably connected to the fixing component (221). The fixing mechanism (22) also includes a conversion structure (24). The clamping part (222) switches between the clamping state and the avoidance state through the conversion structure (24).

8. The nucleic acid amplification device according to claim 7, characterized in that, The conversion structure (24) includes a first groove (241) and a second groove (244) formed on the fixing component (221), a hook (242) connected to the fixing component (221) and a protrusion (243) connected to one end of the pressing part (222). The other end of the pressing part (222) is slidably and rotatably connected to the first groove (241). The protrusion (243) can slide in the second groove (244) and can engage with the hook (242) and disengage from the second groove (244).

9. The nucleic acid amplification device according to claim 1, characterized in that, The support unit (2) further includes a first temperature detection unit, which is used to measure the temperature at the temperature calibration unit (124); or, The carrier (1) includes a second temperature detection unit (13) connected to the temperature calibration unit (124) and used to measure the temperature at the temperature calibration unit (124).

10. The nucleic acid amplification device according to claim 9, characterized in that, The supporting body (21) has a clearance part (2131) for avoiding the first temperature detection unit or the second temperature detection unit (13) and the temperature calibration part (124).

11. The nucleic acid amplification device according to claim 9, characterized in that, The first temperature detection unit is a contact temperature sensor (25) or a non-contact temperature sensor (26).

12. The nucleic acid amplification device according to claim 11, characterized in that, When the first temperature detection unit is a contact temperature sensor (25), the first temperature detection unit and the temperature calibration unit (124) are in elastic contact.

13. The nucleic acid amplification device according to claim 1, characterized in that, The carrier (1) is at least partially located in the first through hole (2211).

14. The nucleic acid amplification device according to claim 13, characterized in that, The first through hole (2211) has a positioning element (2213) on its hole wall for positioning the carrier (1).

15. The nucleic acid amplification device according to claim 14, characterized in that, The upper surface of the fixing mechanism (22) is also provided with a pick-and-place groove (2212) that communicates with the first through hole (2211).

16. The nucleic acid amplification device according to claim 13, characterized in that, The supporting body (21) is at least partially inserted through the first through hole (2211).

17. The nucleic acid amplification device according to claim 1, characterized in that, The carrier (21) includes a cooling body (212) and a cold head (213) connected to the cooling body (212). The carrier (1) can fit tightly against the cold head (213). The cooling body (212) is used to circulate the cooling medium.

18. The nucleic acid amplification device according to claim 1, characterized in that, The carrier (1) has a flat structure.

19. The nucleic acid amplification device according to claim 3, characterized in that, The number of the support parts (2) is one or at least two. When the number of the support parts (2) is at least two, at least two of the support parts (2) can be connected to the cooling mechanism (6) respectively.

20. The nucleic acid amplification device according to claim 1, characterized in that, The support part (2) also includes a drive mechanism for driving the support base (23) to move closer to or away from the carrier (1).

21. The nucleic acid amplification device according to claim 3, characterized in that, The nucleic acid amplification device further includes a guide component (5), which is connected between the support part (2) and the housing (4) and is used to guide the support part (2).

22. The nucleic acid amplification device according to claim 3, characterized in that, The support part (2) includes a pipe joint (29), and the cooling mechanism (6) is connected to the support part (2) through the pipe joint (29).

23. The nucleic acid amplification device according to claim 1, characterized in that, The carrier part (2) also includes a PCB board (20), which is connected to the electrical contact (27).

24. The nucleic acid amplification device according to claim 3, characterized in that, The cooling mechanism (6) is located outside the housing (4).

25. A nucleic acid detection system, characterized in that, The invention includes the nucleic acid amplification device according to any one of claims 1-24 and the detection module (3), wherein the detection module (3) is used to detect the reaction sample.

26. The nucleic acid detection system according to claim 25, characterized in that, It also includes a communication module, and both the nucleic acid amplification device and the detection module (3) are connected to the communication module.

27. The nucleic acid detection system according to claim 25, characterized in that, It also includes an output device, which is connected to the detection module (3).

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