CN118813399A

CN118813399A - Nucleic acid amplification device and nucleic acid amplification system

Info

Publication number: CN118813399A
Application number: CN202310420764.5A
Authority: CN
Inventors: 徐强; 韦嘉; 赵蒙; 徐涛
Original assignee: Guangzhou National Laboratory
Current assignee: Guangzhou National Laboratory
Priority date: 2023-04-18
Filing date: 2023-04-18
Publication date: 2024-10-22
Also published as: WO2024217048A1

Abstract

The present invention relates to a nucleic acid amplification device and a nucleic acid amplification system, the nucleic acid amplification device including: a carrier capable of carrying and heating a reaction sample; and the bearing part is used for bearing the carrier. A nucleic acid detection system comprising the nucleic acid amplification device and a detection module for detecting the reaction sample. The carrier part carries the carrier, and the carrier both can bear the reaction sample, also can heat the reaction sample simultaneously, and the carrier is monolithic structure, does not have clearance and air interface between reaction sample and the carrier, consequently, has improved the heat conduction efficiency between carrier and the reaction sample, and then has improved heating efficiency and detection efficiency.

Description

Nucleic acid amplification device and nucleic acid amplification system

Technical Field

The invention relates to the technical field of medical treatment, in particular to a nucleic acid amplification device and a nucleic acid amplification system.

Background

PCR (polymerase chain reaction) is a molecular biological experimental method for in vitro enzymatic synthesis of specific DNA fragments, and PCR amplification, namely nucleic acid amplification, mainly comprises three repeated thermal cycles of high-temperature denaturation, low-temperature annealing and temperature-adaptive extension.

In the prior art, a nucleic acid amplification system for detecting nucleic acid comprises a heater and a sample containing structure which can be placed on the heater, wherein the sample containing structure is a shell or a tube, and the heater can heat the sample containing structure so as to heat a sample in the sample containing structure. However, due to the air interface between the heated sample holding structure and the heater, the heat conduction efficiency is low, and the heating efficiency and the detection efficiency are low. The thickness of the reaction sample in the shell or the tube body is large, the time required for the uniform temperature of the reaction sample is long, and the reaction sample is slow in temperature rising and reducing speed. The complex structure of the heater prevents heat transfer between the heater and the reaction sample, which also results in slow temperature rise and drop of the reaction sample.

In addition, in order to facilitate control of the heater, it is necessary to detect the temperature of the reaction sample, and the temperature detection method commonly used in the prior art is low in accuracy, resulting in inaccurate detection results.

In addition, in the existing PCR instrument, the temperature rising and falling rate of a reaction solution is slow in the PCR amplification reaction process, so that the detection rate is seriously influenced.

Disclosure of Invention

An object of the present invention is to propose a nucleic acid amplification apparatus to solve at least one of the above problems.

To achieve the above object, a first aspect of the present invention provides a nucleic acid amplification apparatus comprising:

A carrier capable of carrying and heating a reaction sample;

and the bearing part is used for bearing the carrier.

Optionally, the device further comprises a casing, and the bearing part is movably connected to the casing so as to switch between a lofting position and a detecting position.

Optionally, the nucleic acid amplification apparatus further comprises a cooling mechanism for cooling the carrying part.

Optionally, when the bearing part is located at the detection position, the cooling mechanism is communicated with the bearing part.

Optionally, the bearing part is slidably connected to the casing.

Optionally, the bearing part includes:

A carrying body capable of carrying and cooling the carrier;

The fixing mechanism can enable the carrier to be tightly attached to the bearing main body;

The supporting seat can support the bearing main body and the fixing mechanism.

Optionally, the fixing mechanism includes:

The fixing component is connected to the supporting seat;

And the pressing part is connected with the fixing assembly and can be switched between a pressing state and an avoiding state.

Optionally, the compressing part is rotationally connected to the fixing component, the fixing mechanism further comprises a switching structure, and the compressing part is switched between the compressing state and the avoiding state through the switching structure.

Optionally, the conversion structure includes set up in first spout and second spout on the fixed subassembly, connect in the pothook of fixed subassembly and connect in the card of the one end of compressing tightly portion is protruding, the other end slip of compressing tightly portion just rotate connect in first spout, card protruding can be in the second spout slides, and can with the pothook joint and break away from the second spout.

Optionally, the carrier is formed with a receiving cavity for receiving the reaction sample, and the carrier includes a heater.

Optionally, the heater includes a soaking layer in contact with the reaction sample within the containment chamber.

Optionally, the heater further comprises a heating element and a temperature calibration part for reacting the temperature of the heating element.

Optionally, the carrying part further includes a first temperature detecting unit for measuring a temperature at the temperature calibration part; or alternatively, the first and second heat exchangers may be,

The carrier includes a second temperature detection unit connected to the temperature calibration portion and configured to measure a temperature at the temperature calibration portion.

Optionally, the bearing main body is provided with an avoidance portion, and the avoidance portion is used for avoiding the first temperature detection unit or the second temperature detection unit and avoiding the temperature calibration portion.

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

Optionally, when the first temperature detecting unit is a contact temperature sensor, elastic contact is formed between the first temperature detecting unit and the temperature calibration portion.

Optionally, the fixing mechanism is provided with a first through hole, and the carrier is at least partially located in the first through hole.

Optionally, a positioning member for positioning the carrier is disposed on a hole wall of the first through hole.

Optionally, a pick-and-place groove communicated with the first through hole is further formed in the upper surface of the fixing mechanism.

Optionally, the bearing body at least partially penetrates through the first through hole.

Optionally, the carrier further comprises an electrical contact at least partially located in the first through hole to be in electrical contact with the carrier.

Optionally, the electrical contact includes:

power contacts, and/or

A current sense contact and a voltage sense contact.

Optionally, the bearing body comprises a cooling body and a cold head connected with the cooling body, the carrier can be closely attached to the cold head, and the cooling body is used for circulating cooling medium.

Optionally, the carrier is a flat structure.

Optionally, the number of the carrying parts is one or at least two, and when the number of the carrying parts is at least two, at least two carrying parts can be respectively connected with the cooling mechanism.

Optionally, the bearing part further comprises a driving mechanism, and the driving mechanism is used for driving the supporting seat to be close to or far away from the carrier.

Optionally, the nucleic acid amplification apparatus further includes a guide assembly connected between the carrying part and the housing and configured to guide the carrying part.

Optionally, the bearing part comprises a pipeline joint, and the cooling mechanism is communicated with the bearing part through the pipeline joint.

Optionally, the bearing part further comprises a PCB board, and the PCB board is connected with the electrical contact.

Optionally, the cooling mechanism is disposed outside the housing.

It is another object of the present invention to provide a nucleic acid amplification control method to solve at least one of the above problems.

To achieve the object, the second aspect of the present invention adopts the following technical scheme:

a nucleic acid detection system comprising the nucleic acid amplification device and a detection module for detecting the reaction sample.

Optionally, the kit further comprises a communication module, wherein the nucleic acid amplification device and the detection module are both connected with the communication module.

Optionally, the device further comprises an output device, and the output device is connected with the detection module.

Therefore, according to the technical scheme provided by the invention, the carrier part carries the carrier, the carrier can carry the reaction sample and can heat the reaction sample, and the carrier is of an integral structure, and a gap and an air interface do not exist between the reaction sample and the carrier, so that the heat conduction efficiency between the carrier and the reaction sample is improved, and the heating efficiency and the detection efficiency are further improved. The nucleic acid amplification device provided by the invention can realize rapid temperature rise and fall of a reaction sample, and shortens the detection time.

Drawings

FIG. 1 is a schematic diagram of a nucleic acid amplification system according to an embodiment of the present invention;

FIG. 2 is a schematic diagram showing the structure of a nucleic acid amplification system (cooling mechanism removed) according to an embodiment of the present invention;

FIG. 3 is a cross-sectional view of a nucleic acid amplification system provided by an embodiment of the present invention;

FIG. 4a is a schematic diagram of a part of a nucleic acid amplification system according to an embodiment of the present invention;

FIG. 4b is a schematic diagram of a partial nucleic acid amplification apparatus according to an embodiment of the present invention;

FIG. 4c is an exploded view of a carrier provided by an embodiment of the present invention;

FIG. 4d is an exploded view of another view of the carrier provided by an embodiment of the present invention;

Fig. 5 is a schematic structural diagram of a bearing body according to an embodiment of the present invention;

Fig. 6 is a schematic structural diagram of a bearing part according to an embodiment of the present invention;

FIG. 7 is an enlarged view of a portion of FIG. 6 at A;

fig. 8 is a schematic structural view of a bearing part removing pressing part according to an embodiment of the present invention;

FIG. 9 is a schematic view of a structure of a pressing portion with a bearing portion removed according to an embodiment of the present invention;

FIG. 10a is a schematic view of a carrier provided by an embodiment of the present invention;

FIG. 10b is a schematic diagram of another view of a carrier provided by an embodiment of the present invention;

FIG. 11 is a cross-sectional view of a part of a nucleic acid amplification apparatus according to an embodiment of the present invention;

FIG. 12 is a graph showing the temperature profile of a reaction sample provided in an example of the present invention.

In the figure:

1. a carrier; 11. a receiving chamber; 12. a heater; 121. a soaking layer; 122. a heating member; 123. an electrical contact; 124. a temperature calibration unit; 125. an external electrical connection contact; 126. an electrical connection lead; 13. a second temperature detection unit;

2. A carrying part;

21. A carrying body; 211. a mounting plate; 212. a cooling body; 2121. a fin; 2122. a channel; 213. a cold head; 2131. an avoidance unit;

22. A fixing mechanism;

221. a fixing assembly; 2211. a first through hole; 2212. a taking and placing groove; 2213. a positioning piece; 2214. a fixing plate; 2215. a fixing strip;

222. a pressing part; 2221. a light-transmitting hole;

23. A support base; 231. a cooling tank; 232. a base;

24. a switching structure; 241. a first chute; 242. a clamping hook; 243. a clamping protrusion; 244. a second chute;

25. A contact temperature sensor; 26. a non-contact temperature sensor; 27. an electrical contact; 29. a pipe joint; 20. a PCB board;

3. A detection module;

4. A housing;

5. a guide assembly; 51. a slide rail; 52. a slide block;

6. A cooling mechanism; 61. a male connector.

Detailed Description

The technical scheme of the invention is further described below by the specific embodiments with reference to the accompanying drawings. It is to be understood that the specific embodiments described herein are merely illustrative of the invention and are not limiting thereof. It should be further noted that, for convenience of description, only some, but not all of the drawings related to the present invention are shown.

In the present invention, directional terms such as "upper", "lower", "left", "right", "inner" and "outer" are used for convenience of understanding, and thus do not limit the scope of the present invention unless otherwise specified.

In the present invention, unless expressly stated or limited otherwise, a first feature "above" or "below" a second feature may include both the first and second features being in direct contact, as well as the first and second features not being in direct contact but being in contact with each other through additional features therebetween. Moreover, a first feature being "above," "over" and "on" a second feature includes the first feature being directly above and obliquely above the second feature, or simply indicating that the first feature is higher in level than the second feature. The first feature being "under", "below" and "beneath" the second feature includes the first feature being directly under and obliquely below the second feature, or simply means that the first feature is less level than the second feature.

In the description of the present invention, unless explicitly stated and limited otherwise, the terms "connected," "connected," and "fixed" are to be construed broadly, and may be, for example, fixedly connected, detachably connected, or integrally formed; can be mechanically or electrically connected; can be directly connected or indirectly connected through an intermediate medium, and can be communicated with the inside of two elements or the interaction relationship of the two elements. The specific meaning of the above terms in the present invention will be understood in specific cases by those of ordinary skill in the art.

The embodiment provides a nucleic acid amplification device which can be used for PCR amplification and nucleic acid detection.

As shown in fig. 1 to 10a, a nucleic acid amplification apparatus provided in this embodiment includes a carrier 1 and a carrying part 2, the carrier 1 being capable of carrying and heating a reaction sample, the carrying part 2 being for carrying the carrier 1.

The carrier 1 is carried by the carrier part 2, the carrier 1 can carry the reaction sample and can heat the reaction sample, the carrier 1 is of an integral structure, and no gap or air interface exists between the reaction sample and the carrier 1, so that the heat conduction efficiency between the carrier 1 and the reaction sample is improved, and the heating efficiency and the detection efficiency are further improved.

As shown in fig. 2, the nucleic acid amplification system may further include a housing 4, where the carrying portion 2 is movably connected to the housing 4 to switch between the sample loading position and the detection position. When the carrying part 2 is positioned at the lofting position, the carrier 1 carrying the reaction sample can be placed on the carrying part 2; when the carrying part 2 is located at the detection position, the reaction sample can be detected.

Alternatively, the carrying part 2 is slidably connected to the casing 4, so that the carrying part 2 is stably switched between the lofting position and the detecting position.

As shown in fig. 3 and 4a, in order to facilitate sliding of the carrying part 2, the nucleic acid amplification apparatus optionally further comprises a guide member 5, wherein the guide member 5 is connected between the carrying part 2 and the housing 4 and is used for guiding the carrying part 2.

Specifically, the guide assembly 5 includes a slide rail 51 and a slider 52, the slide rail 51 is connected to the carrying portion 2, the slider 52 is connected to the casing 4, and the slider 52 is slidably connected to the slide rail 51. Of course, in other alternative embodiments, the slider 52 may be connected to the carrying portion 2, and the slide rail 51 may be connected to the casing 4.

As shown in fig. 1, the nucleic acid amplification apparatus optionally further includes a cooling mechanism 6, the cooling mechanism 6 being for cooling the carrier part 2. The cooling mechanism 6 cools the carrier 2, and the carrier 1 is placed on the carrier 2, so that the carrier 2 can cool the carrier 1, and thus the reaction sample in the carrier 1. The carrier 1 can also heat the reaction sample therein, so that the reaction sample can be heated, cooled and kept warm in the carrier 1, thereby realizing amplification.

Alternatively, the cooling mechanism 6 communicates with the carrier 2 when the carrier 2 is in the detection position. When the carrier 2 moves in the housing 4 and moves away from the detection position, the carrier 2 is not connected to the cooling mechanism 6, and therefore, a pipeline connecting the cooling mechanism 6 and the carrier 2 can be simplified. Optionally, the cooling mechanism 6 is disposed outside the housing 4.

As shown in fig. 3 and 4a, the carrier part 2 comprises a pipe joint 29, and the cooling mechanism 6 communicates with the carrier part 2 through the pipe joint 29. The pipe joint 29 may be a female joint, the cooling mechanism 6 may include a male joint 61, the male joint 61 may be disposed through the casing 4, and the female joint and the male joint 61 may be plugged. When the carrying part 2 moves to the detecting position, the male connector 61 and the female connector are inserted, and when the carrying part 2 moves and leaves the detecting position, the male connector 61 and the female connector are gradually separated.

As shown in fig. 4b, it is understood that the number of the pipe joint 29 and the male joint 61 is two, and that one pipe joint 29 may be connected to one male joint 61 and the other pipe joint 29 may be connected to the other male joint 61, thereby achieving injection of the cooling medium and return of the cooling medium.

As shown in fig. 4a, 4 c-6, the carrying part 2 includes a carrying body 21, a fixing mechanism 22 and a supporting seat 23. The carrier body 21 is capable of carrying and cooling the carrier 1. The fixing mechanism 22 can make the carrier 1 tightly attached to the carrying body 21, so as to avoid a gap between the carrier 1 and the carrying body 21, and further improve the heat transfer efficiency between the carrier 1 and the carrying body 21. The support base 23 can support the carrier body 21 and the fixing mechanism 22. Optionally, the carrying portion 2 may further include a base 232, the base 232 is connected to the lower side of the supporting seat 23, and the sliding rail 51 is connected to the lower side of the base 232.

Alternatively, the supporting seat 23 may be provided with a cooling slot 231 opened toward the carrying body 21, and the carrying body 21 is partially disposed in the cooling slot 231. The pipe joint 29 penetrates through the sidewall of the support base 23 and communicates with the cooling tank 231 to introduce the cooling medium into the cooling tank 231 and directly cool the bearing body 21 located in the cooling tank 231.

As shown in fig. 5, when the carrier 1 is cooled by circulating the cooling medium in 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 may be capable of being abutted against the cold head 213. Further, the carrier 1 is placed on the upper surface of the coldhead 213. The cooling body 212 is used for circulating a cooling medium. The cooling medium cools the cooling body 212, and the cooling body 212 cools the coldhead 213, and thus the carrier 1 placed on the coldhead 213.

In a specific embodiment, the cooling body 212 includes a plurality of fins 2121 disposed in parallel, and channels 2122 through which the cooling medium flows are formed between the fins 2121, where the fins 2121 can increase the contact area between the cooling medium and the carrier body 21, so as to accelerate cooling of the cold carrier body 21.

Preferably, a mounting plate 211 is further disposed between the cooling body 212 and the cold head 213, and the mounting plate 211 is covered on an opening of the cooling tank 231 to prevent the cooling medium from flowing out.

As shown in fig. 4c, 4d and 6, the fixing mechanism 22 includes a fixing component 221 and a pressing portion 222, the fixing component 221 is connected to the supporting seat 23 or to the base 232, and the pressing portion 222 is connected to the fixing component 221 and is capable of being switched between a pressing state and a retreating state. When the pressing part 222 is in a pressed state, the carrier 1 can be pressed against the coldhead 213; when the hold-down 222 is in the retracted state, the carrier 1 can be placed on the coldhead 213 or removed from the coldhead 213.

As shown in fig. 4c, 4d and 6, the pressing portion 222 is preferably plate-shaped, so that the pressing portion 222 presses the carrier 1 uniformly throughout, and thus the carrier 1 is pressed against the carrying portion 2 throughout. The pressing portion 222 is further provided with a light passing hole 2221, and fluorescence is detected through the light passing hole 2221.

The compressing part 222 is rotatably connected to the fixing assembly 221, and the fixing mechanism 22 further includes a switching structure 24, where the compressing part 222 is switched between a compressing state and an avoiding state by the switching structure 24. When the pressing portion 222 rotates to be in contact with the carrier 1, the pressing portion 222 can press the carrier 1 by the switching structure 24, and is switched to the escape state by the switching structure 24.

As shown in fig. 4c, 4d and 6-8, the compressing structure converting structure 24 includes a first chute 241 and a second chute 244 opened on the fixing component 221, a hook 242 connected to the fixing component 221, and a clamping protrusion 243 connected to one end of the compressing portion 222, wherein the other end of the compressing portion 222 is slidably and rotatably connected to the first chute 241, the clamping protrusion 243 can slide in the second chute 244, the clamping protrusion 243 can be clamped with the hook 242 and separated from the second chute 244, and the compressing portion 222 is slidably and rotatably connected to the first chute 241.

When the compressing portion 222 is in a compressed state, the locking protrusion 243 is locked with the locking hook 242, and the compressing portion 222 can be kept in a compressed state. When the compressing portion 222 is switched from the compressing state to the avoiding state, firstly, the compressing portion 222 is pushed in the first direction in the first sliding groove 241 and the second sliding groove 244, so that the hook 242 and the clamp 243 are separated from each other, then, one end of the compressing portion 222 can be lifted, so that the clamp 243 is separated from the second sliding groove 244, and meanwhile, the other end of the compressing portion 222 rotates in the first sliding groove 241 until the compressing portion 222 rotates to the avoiding position. It will be appreciated that the hold-down 222 in the retracted state is not located at a particular position, as long as the carrier 1 can be taken and placed.

Preferably, the hook 242 is located at one end of the second sliding groove 244, and the hook 243 can be separated from the second sliding groove 244 along with the rotation of the pressing portion 222 when sliding to the other end of the second sliding groove 244. One end of the pressing part 222 may be connected to a rotating shaft, and the rotating shaft slides and is rotatably disposed in the first sliding groove 241.

Optionally, switching structures 24 are provided along both sides of the second direction of the fixing assembly 221 so that the compressing part 222 is stably located in a compressed state. The second direction is perpendicular to the first direction, and both the first direction and the second direction are parallel to the surface of the carrier 1 placed on the coldhead 213.

Optionally, the fixing assembly 221 includes a fixing plate 2214 and a fixing strip 2215 connected to the fixing plate 2214, and the first sliding groove 241 and the second sliding groove 244 are formed on the fixing strip 2215. The number of the fixing strips 2215 may be two, the two fixing strips 2215 are spaced apart along the second direction, and the compressing part 222 is disposed between the two fixing strips 2215.

The fixing mechanism 22 is provided with a first through hole 2211, and the carrier 1 is at least partially positioned in the first through hole 2211. Preferably, a portion in the thickness direction of the carrier 1 is provided on the first through hole 2211 so that the plate-shaped pressing portion 222 is in contact with the carrier 1 to press the carrier 1. Of course, in other embodiments, the carrier 1 may be disposed entirely within the first through hole 2211, and the pressing portion 222 may be provided with a protrusion, and the surface of the carrier 1 may be contacted by the protrusion, so as to press the carrier 1.

Alternatively, the bearing body 21 may also at least partially penetrate through the first through hole 2211. Of course, in other alternative embodiments, the carrying body 21 may also be located below the fixing mechanism 22, and the carrier 1 is connected to the carrying body 21 through the first through hole 2211. Optionally, the cold head 213 is at least partially located in the first through hole 2211.

In the present embodiment, the first through hole 2211 is disposed on the fixing component 221, and further, the first through hole 2211 is disposed on the fixing plate 2214.

As shown in fig. 8, a positioning member 2213 for positioning the carrier 1 is provided on the wall of the first through hole 2211. The number of the positioning pieces 2213 may be plural, and the plural positioning pieces 2213 are disposed at intervals along the circumferential direction of the first through hole 2211. The positioning member 2213 may be a protruding column connected to a hole wall of the first through hole 2211. The positioning piece 2213 can position the carrier 1, so that the carrier 1 is accurately aligned with the cold head 213, and the positioning piece 2213 can also reduce the contact area between the carrier 1 and the fixing plate 2214, thereby reducing the heat exchange between the fixing plate 2214 and the carrier 1, and ensuring high temperature uniformity of the carrier 1.

The upper surface of the fixing mechanism 22 is also provided with a pick-and-place groove 2212 communicated with the first through hole 2211. The pick-and-place groove 2212 facilitates an operator or an automation device to contact the side surface of the carrier 1, thereby clamping the side surface of the carrier 1 and facilitating the pick-and-place of the carrier 1. Optionally, pick-and-place slots 2212 are formed on two sides of the through hole along the second direction.

In the present embodiment, the number of the carrying parts 2 is one, however, in other alternative embodiments, the number of the carrying parts 2 may be at least two, and when the number of the carrying parts 2 is at least two, at least two carrying parts 2 may be connected to the cooling mechanism 6, for example, as shown in fig. 1, four carrying parts 2 are provided.

In this embodiment, the cooling mechanism 6 is in continuous contact with the carrier 1, but of course, in other alternative embodiments, the carrying part 2 further comprises a driving mechanism for driving the support seat 23 towards or away from the carrier 1 so as to bring the cooling mechanism 6 into intermittent contact with the carrier 1.

The cooling mechanism 6 may not be in contact with the carrier 1, such as when the reaction sample is in a temperature rising stage. The cooling mechanism 6 is in contact with the carrier 1 when the reaction sample is in a cooling stage. When the reaction sample is in the temperature maintaining 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 be kept out of contact with the carrier 1, and the temperature of the reaction sample may be controlled by the heating function of the carrier 1.

As shown in fig. 10a, the carrier 1 is formed with a receiving chamber 11 for receiving a reaction sample, and the carrier 1 includes a heater 12. The carrier 1 is of an integral structure, and a gap and an air interface do not exist between the reaction sample and the heater 12, so that the heat transfer speed between the carrier 1 and the reaction sample is improved, the nucleic acid amplification process is accelerated, and the detection efficiency is improved.

Alternatively, the carrier 1 may be a flat structure, and further, the accommodating cavity 11 may be a flat structure, it is understood that the flat structure may mean that the dimension in the thickness direction of the accommodating cavity 11 is much smaller than the dimension in the width or length direction, and as an example, the accommodating cavity 11 is a cuboid, and the ratio of the length to the thickness of the cuboid may be greater than 5:1, such as 90:1, for example, the dimension of the accommodating chamber 11 in the thickness direction may be 0.3-1.0mm, and the width and length of the accommodating chamber 11 may be about 10mm and 20mm, respectively, wherein the dimension in the thickness direction is the arrangement direction of the heating member 122 and the accommodating chamber 11. As an example, the housing 11 may also have a cylindrical structure with a diameter to thickness ratio greater than 5:1, for example, 0.3-1.0mm in thickness and 5-20mm in diameter. Of course, the cross section of the housing chamber 11 may be polygonal or elliptical, etc. Of course, the cross section of the housing chamber 11 may be polygonal or elliptical, etc.

Specifically, the heater 12 is in direct contact with the reaction sample in the accommodation chamber 11. There is no other conductive interface between the reaction sample and the heater 12, thereby reducing the conductive interface between the heater 12 and the receiving chamber 11 and further improving the conduction efficiency. Meanwhile, no interface exists between the heater 12 and the reaction sample, so that the thermal resistance is small, and the rapid heat conduction and the higher-speed temperature control can be realized.

The heater 12 includes a soaking layer 121, and the soaking layer 121 is in contact with the reaction sample in the accommodating chamber 11. The soaking layer 121 can ensure uniform heat conduction in both the longitudinal and transverse directions (i.e., the thickness direction of the reaction sample and the plane perpendicular to the thickness direction), and ensure the temperature uniformity of the sample liquid. Alternatively, the soaking layer 121 is made of an electrically conductive material or an insulating material, for example, the soaking layer 121 is made of an electrically conductive material such as aluminum, copper, or an insulating material such as high thermal conductivity ceramic.

As shown in fig. 9-11, the carrier 2 optionally further comprises electrical contacts 27, the electrical contacts 27 being at least partially located in the first through holes 2211 for electrical contact with the carrier 1. Optionally, the electrical contact 27 is disposed proximate to the wall of the first through-hole 2211. The arrangement of the electrical contacts 27 can improve the structural compactness of the carrier 2. Optionally, the heater 12 further includes a heating element 122 and an electrical contact 123 electrically connected to the heating element 122, and the electrical contact 27 is electrically connected to the electrical contact 123. The heating element 122 may be a resistance wire or the like.

The carrier 2 may further comprise a PCB board 20, the PCB board 20 being connected to the electrical contacts 27, thereby powering the electrical contacts 27 through the PCB board 20, and transmitting current and voltage signals.

In the present embodiment, the heating member 122 is measured by resistance temperature measurement, and power is supplied to the heating member 122 through the electrical contact 27 to heat the heating member 122, optionally, the electrical contact 27 includes a power supply contact, a current detection contact, and a voltage detection contact. The power supply contact is used for supplying power to the heating element 122, the current detection contact and the voltage detection contact are used for respectively detecting the current I and the voltage U of the heating element 122, and then the resistance R of the heating element 122 at the temperature T can be obtained by utilizing R=U/I. According to the formula R=R ₀ (1+αΔT) (where ΔT=T-T ₀, R is the resistance value of the heating element 122 at temperature T, T ₀ is the nominal temperature, and R ₀ is the resistance value at the nominal temperature (the resistance value at the nominal temperature is simply referred to as the nominal resistance value), it is understood that the nominal resistance is the nominal temperature at which the declared (or noted) resistance value is true, and the nominal temperature is arbitrarily selected as desired, and α is the temperature coefficient of resistance of the material) the temperature value of the heating element 122 at the resistance R is obtained.

Of course, in other alternative embodiments, the electrical contacts 27 comprise power supply contacts, or only current detection contacts and voltage detection contacts.

There is a specific relation between the resistance of the heating element 122 and its temperature as shown in the above formula, so that the real-time resistance change of the heating element 122 of the carrier 1 is measured while heating, and the average temperature of the heating element 122 is deduced by simply referring to the resistance value at the nominal temperature of the resistance value at the nominal temperature and the resistance temperature coefficient. The temperature is calculated by monitoring the resistance value of the heating element 122, and compared with the temperature of the heating element 122 measured by adopting a temperature sensor, the current temperature of the carrier 1 is reflected in real time without delay, so that the temperature can be used for quickly feedback-controlling the carrier 1 and the temperature of a reaction sample. The disadvantage of this method is that for the same type of resistance, such as copper wire resistance, the nominal resistance and the temperature coefficient of resistance differ slightly between the resistances, resulting in a slight difference between the temperature coefficient of resistance and the nominal resistance between the individual heating elements 122, which may cause temperature measurement errors.

To avoid the above-described errors, the heater 12 may optionally further include a temperature calibration portion 124 for reflecting the temperature of the heating member 122. The temperature calibration part 124 can represent the temperature of the heating element 122, so that the temperature of the temperature calibration part 124 can be detected by other methods, the temperature coefficient of resistance and the nominal resistance value can be calibrated, and the accurate temperature of the heating element 122 can be detected by a resistance temperature measurement method. Alternatively, the temperature calibration part 124 is provided at the bottom of the carrier 1.

To detect the temperature of the heating member 122, the carrying part 2 may optionally further include a temperature detecting unit for detecting the temperature of the temperature calibrating part 124. The temperature detection unit may be a first temperature detection unit for measuring the temperature at the temperature calibration part 124. The first temperature detecting unit may be electrically connected with the PCB board 20. The first temperature detecting unit can be repeatedly used, so that the cost is saved. Specifically, as shown in fig. 8, the first temperature detecting unit is a non-contact temperature sensor 26, such as an infrared sensor, or the like. The first temperature detection unit may also be a contact temperature sensor 25, and the contact temperature sensor 25 performs temperature detection by contacting with the temperature calibration part 124.

When the first temperature detecting unit is the contact temperature sensor 25, the first temperature detecting unit is in elastic contact with the temperature calibration portion 124, so as to ensure that the first temperature detecting unit is in complete contact with the temperature calibration portion 124. For example, the contact temperature sensor 25 is electrically connected to the PCB 20 through an elastic member such as a spring.

Of course, in other alternative embodiments, the first temperature detecting unit may not be included, and the carrier 1 may include the second temperature detecting unit 13 connected to the temperature calibration part 124 and used for measuring the temperature at the temperature calibration part 124, and the second temperature detecting unit 13 may be discarded together with the carrier 1 as a consumable.

As shown in fig. 10b, when the second temperature detecting unit 13 is attached to the carrier 1, the nucleic acid amplification apparatus may optionally further include external electrical connection contacts 125 and electrical connection leads 126, the number of external electrical connection contacts 125 and electrical connection leads 126 may be two, the number of two temperature calibration parts 124 is two, and insulation is provided between the two temperature calibration parts 124. Two external electrical connection contacts 125 are respectively located at the sides of the two temperature calibration portions 124 away from each other, one external connection contact is electrically connected with one temperature calibration portion 124 through one electrical connection lead 126, and the other external connection contact is electrically connected with the other temperature calibration portion 124 through the other electrical connection lead 126.

The temperature calibration part 124 is electrically connected with the outside at the external electrical connection contact 125 through the electrical connection lead 126, wherein the diameter of the electrical connection lead 126 is smaller than that of the temperature calibration part 124 and the external electrical connection contact 125, thereby reducing the heat loss generated by the temperature calibration part 124 through the electrical connection lead 126, the temperature calibration part 124 can embody the temperature of the heating element 122, the second temperature detection unit 13 realizes good electrical and thermal contact with the temperature calibration part 124 through a welding spot, 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 leads to the resistance change of the second temperature detection unit 13, and the resistance change of the second temperature detection unit 13 is detected at the external electrical connection contact 125 in real time, so that the temperature detection can be realized.

In the prior art, the temperature of the reaction sample is detected by the isothermal detection unit of the temperature sensor, but because heat is transferred from the reaction sample to the isothermal detection unit for a certain time, the detection result measured by the isothermal detection unit has a temperature measurement delay of 1-2s under normal conditions, and the temperature change of the reaction sample can reach more than 30 ℃ in the rapid temperature rise and fall process, so that the carrier 1 is relatively difficult to control by the isothermal detection unit in the rapid temperature rise and fall process. In the present embodiment, the temperature detected by the resistance thermometry is calibrated by the first temperature detection unit or the second temperature detection unit 13, specifically, the nominal resistance value and the resistance temperature coefficient are calibrated. When the first temperature detection unit or the second temperature detection unit 13 is used for calibration, the temperature of the temperature detection unit and the temperature of the reaction sample tend to be always kept for 1-2s at a certain temperature, so that the accurate temperature under the resistor R is obtained, and the nominal resistance value and the resistance temperature coefficient are calibrated.

In order to more clearly describe the process of correcting the resistance thermometry, a process of calibrating the resistance thermometry by the temperature detection unit in an actual test is shown in conjunction with fig. 12. Before calibrating the temperature values, an initial RT temperature profile, i.e. a temperature preset profile, is preset, and then a small current, e.g. less than 1 ma, is applied to the heating element 122 of the carrier 1. Wherein a small current is applied in order to read the resistance of the heating element 122 without heating the heating element 122.

First calibration: the temperature detecting unit detects a first temperature calibration value T ₁, and the resistance detecting unit detects a first voltage U ₁ and a first current I ₁ of the heating element 122 at the temperature T ₁, and can obtain a resistance R ₁ of the heating element 122 at the temperature T ₁ according to r=u/I.

Second calibration: then, the temperature detecting unit detects a second temperature calibration value T ₂, and the resistance detecting unit 5 detects a second voltage U ₂ and a second current I ₂ of the heating element 122 at the temperature of T ₂, so that the resistance R ₂ of the heating element 122 at the temperature of T ₂ can be obtained according to r=u/I.

Finally, according to two sets of binary once equations: r ₁＝R₀(1+αΔT₁) and R ₂＝R₀(1+αΔT₂), specific values of R ₀ and α are obtained, that is, an accurate R-T curve is obtained, and the temperature of the heating element 122 measured by the resistance temperature measurement method can be used as feedback for accurate temperature control.

With continued reference to fig. 12, when the first temperature calibration value is obtained, the temperature calibration value may be considered as a nominal resistance value, and thus, according to the temperature calibration value, a correction may be performed on R ₀ in the formula r=r ₀ (1+αΔt), so as to implement a first calibration on the temperature value measured by the resistance thermometry (such as a first fluctuation of the temperature value curve measured by the resistance thermometry in fig. 12 after the first calibration is performed).

The temperature calibration value can be detected in the whole process of nucleic acid amplification, so that the temperature can be calibrated for multiple times in the subsequent process, and the detection precision is further improved.

The temperature of the carrier 1 is calibrated by combining the two components, so that the temperature of the carrier 1 can be quickly and accurately controlled, and the aim of accurately controlling the temperature is fulfilled.

As shown in fig. 11, the carrier body 21 is provided with a avoidance portion 2131, and the avoidance portion 2131 is used for avoiding the first temperature detection unit or the second temperature detection unit 13, and the avoidance temperature calibration portion 124. The relief portion 2131 may be a groove, a hole, or the like provided in the cooling mechanism 6, and as shown in fig. 5, the relief portion 2131 is opened in the cold head 213. The avoiding portion 2131 can prevent the cooling mechanism 6 from affecting the temperature of the temperature calibration portion 124, and ensure that the temperature calibration portion 124 accurately reflects the temperature of the heating element 122.

Referring to fig. 3, the present embodiment further provides a nucleic acid detection system, which includes the nucleic acid amplification apparatus and a detection module 3, where the detection module 3 is used for detecting a reaction sample. The detection module 3 may be a fluorescence detection unit or the like.

The nucleic acid detecting system further includes a communication module, and the nucleic acid amplification apparatus and the detecting module 3 are connected to the communication module so as to control the detecting module 3, the heating member 122 of the carrier 1, and the cooling mechanism 6.

The nucleic acid detecting system also comprises an output device such as a computer, and the output device is connected with the detecting module 3 so as to output related data.

While the invention has been described in detail in the foregoing general description, embodiments and experiments, it will be apparent to those skilled in the art that modifications and improvements can be made thereto. Accordingly, such modifications or improvements may be made without departing from the spirit of the invention and are intended to be within the scope of the invention as claimed.

Claims

1. A nucleic acid amplification apparatus comprising:

A carrier (1), the carrier (1) being capable of carrying and heating a reaction sample;

-a carrier part (2), the carrier part (2) being adapted to carry the carrier (1).

2. The nucleic acid amplification apparatus as set forth in claim 1, further comprising a housing (4), wherein the carrying portion (2) is movably connected to the housing (4) to switch between a loft position and a detection position.

3. The nucleic acid amplification apparatus according to claim 2, further comprising a cooling mechanism (6), the cooling mechanism (6) being configured to cool the carrying portion (2).

4. The nucleic acid amplification apparatus according to claim 3, wherein the cooling mechanism (6) communicates with the carrying portion (2) when the carrying portion (2) is located at the detection position.

5. The nucleic acid amplification apparatus according to claim 2, wherein the carrier (2) is slidably connected to the housing (4).

6. The nucleic acid amplification apparatus according to any one of claims 1 to 5, wherein the carrier (2) includes:

-a carrying body (21) capable of carrying and cooling said carrier (1);

-a fixing means (22), said fixing means (22) being capable of bringing said carrier (1) into close proximity with said carrying body (21);

-a support seat (23), said support seat (23) being able to support said carrying body (21) and said fixing means (22).

7. The nucleic acid amplification apparatus according to claim 6, wherein the fixing mechanism (22) includes:

-a fixing assembly (221), said fixing assembly (221) being connected to said support seat (23);

and a pressing part (222), wherein the pressing part (222) is connected with the fixed assembly (221) and can be switched between a pressing state and a avoiding state.

8. The nucleic acid amplification apparatus of claim 7, wherein the pressing portion (222) is rotatably connected to the fixing member (221), the fixing mechanism (22) further includes a switching structure (24), and the pressing portion (222) is switched between the pressing state and the avoiding state by the switching structure (24).

9. The nucleic acid amplification apparatus of claim 8, wherein the switching structure (24) includes a first chute (241) and a second chute (244) that are opened on the fixing member (221), a hook (242) connected to the fixing member (221) and a locking protrusion (243) connected to one end of the pressing portion (222), the other end of the pressing portion (222) is slidably and rotatably connected to the first chute (241), and the locking protrusion (243) is slidably provided in the second chute (244) and is capable of being locked to and unlocked from the second chute (244) by the hook (242).

10. The nucleic acid amplification apparatus according to claim 6, wherein the carrier (1) is formed with a receiving chamber (11) for receiving the reaction sample, and the carrier (1) includes a heater (12).

11. The nucleic acid amplification apparatus as set forth in claim 10, wherein the heater (12) includes a soaking layer (121), the soaking layer (121) being in contact with the reaction sample in the accommodation chamber (11).

12. The nucleic acid amplification apparatus according to claim 10, wherein the heater (12) further comprises a heating member (122) and a temperature calibration portion (124) for reacting the temperature of the heating member (122).

13. The nucleic acid amplification apparatus as set forth in claim 12, characterized in that the carrying part (2) further includes a first temperature detection unit for measuring a temperature at the temperature calibration part (124); or alternatively, the first and second heat exchangers may be,

The carrier (1) comprises a second temperature detection unit (13) connected to the temperature calibration part (124) and for measuring the temperature at the temperature calibration part (124).

14. The nucleic acid amplification apparatus according to claim 13, wherein the carrier body (21) is provided with an avoidance portion (2131), and the avoidance portion (2131) is configured to avoid the first temperature detection unit or the second temperature detection unit (13) and to avoid the temperature calibration portion (124).

15. The nucleic acid amplification apparatus of claim 13, wherein the first temperature detection unit is a contact temperature sensor (25) or a noncontact temperature sensor (26).

16. The nucleic acid amplification apparatus according to claim 15, wherein when the first temperature detection unit is a contact temperature sensor (25), elastic contact is made between the first temperature detection unit and the temperature calibration part (124).

17. The nucleic acid amplification apparatus as set forth in claim 6, wherein the fixing mechanism (22) is provided with a first through-hole (2211), and the carrier (1) is at least partially located in the first through-hole (2211).

18. The nucleic acid amplification apparatus as set forth in claim 17, characterized in that a positioning member (2213) for positioning the carrier (1) is provided on a wall of the first through hole (2211).

19. The nucleic acid amplification apparatus as set forth in claim 18, wherein the upper surface of the fixing mechanism (22) is further provided with a pick-and-place groove (2212) communicating with the first through hole (2211).

20. The nucleic acid amplification apparatus as set forth in claim 17, wherein the carrier body (21) is at least partially disposed through the first through hole (2211).

21. The nucleic acid amplification apparatus as set forth in claim 17, characterized in that the carrier (2) further includes an electrical contact (27), the electrical contact (27) being located at least partially in the first through hole (2211) to be in electrical contact with the carrier (1).

22. The nucleic acid amplification apparatus as set forth in claim 21, wherein the electrical contact (27) includes:

power contacts, and/or

A current sense contact and a voltage sense contact.

23. The nucleic acid amplification apparatus according to claim 6, wherein the carrier body (21) includes a cooling body (212) and a cold head (213) connected to the cooling body (212), the carrier (1) being capable of being brought into close contact with the cold head (213), and the cooling body (212) is for circulating a cooling medium.

24. The nucleic acid amplification apparatus according to claim 1, wherein the carrier (1) has a flat structure.

25. The nucleic acid amplification apparatus according to claim 3, wherein the number of the carrying parts (2) is one or at least two, and when the number of the carrying parts (2) is at least two, at least two of the carrying parts (2) are connectable to the cooling mechanism (6), respectively.

26. The nucleic acid amplification apparatus as set forth in claim 6, wherein the carrying part (2) further includes a driving mechanism for driving the support base (23) toward or away from the carrier (1).

27. A nucleic acid amplification apparatus according to claim 3, further comprising a guide assembly (5), the guide assembly (5) being connected between the carrier (2) and the housing (4) and being adapted to guide the carrier (2).

28. The nucleic acid amplification apparatus according to claim 3, wherein the carrier part (2) includes a pipe joint (29), and the cooling mechanism (6) communicates with the carrier part (2) through the pipe joint (29).

29. The nucleic acid amplification apparatus as set forth in claim 21, characterized in that the carrier part (2) further includes a PCB board (20), the PCB board (20) being connected with the electrical contacts (27).

30. The nucleic acid amplification apparatus according to claim 3, wherein the cooling mechanism (6) is provided outside the housing (4).

31. A nucleic acid detection system comprising the nucleic acid amplification apparatus of any one of claims 1 to 30 and a detection module (3), the detection module (3) being configured to detect the reaction sample.

32. The nucleic acid detection system of claim 31, further comprising a communication module, wherein the nucleic acid amplification apparatus and the detection module (3) are both connected to the communication module.

33. The nucleic acid detection system of claim 31, further comprising an output device coupled to the detection module (3).