A carrier and kit

Abstract

The present application relates to a kind of carrier and kit, carrier includes oppositely arranged first wall and second wall, and the side wall between the first wall and the second wall is arranged, the first wall, the second wall and the side wall form sample containing cavity, the sample containing cavity is flat structure, at least part of the side wall is light-transmitting.Reagent carrying part and carrier are included in kit, reagent carrying part is at least used to carry reagent.Sample containing cavity is flat structure, will make the thickness of reaction sample in sample containing cavity very thin, the center distance of reaction sample is very small from the surface of liquid, when carrier is heated, the temperature of reaction sample can reach consistent in very short time, heat transfer efficiency is high, so that the temperature rising and falling speed of reaction sample and detection efficiency are greatly improved.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of in vitro diagnosis, in particular to a carrier and a kit. BACKGROUND

[0002] PCR (Polymerase Chain Reaction) refers to a molecular biology experimental method for in vitro enzymatic synthesis of specific DNA fragments, which is mainly composed of three steps of high-temperature denaturation, low-temperature annealing and suitable temperature extension repeated heat cycle. Before PCR amplification, the reaction sample needs to be put into a carrier, wherein the reaction sample is formed by mixing the collected throat swab or nose swab sample and the reagent for PCR amplification. During PCR amplification, the reaction sample needs to be heated by a heater, so that the reaction sample enters the high-temperature denaturation and stays in the suitable temperature extension stage.

[0003] The carrier in the prior art is a tube structure such as an ep tube, the area of the carrier for containing the reaction sample has a large diameter, the uniform heating speed is slow, and the temperature rising and falling speed of the reaction sample is slow. In addition, there is a groove on the bottom plate to form a containing area for containing the reaction sample, and the thickness of the bottom plate is relatively thick, so it is difficult to realize the rapid temperature rising and falling of the reaction sample.

[0004] The preparation of the reaction sample is operated by professional testers, which is highly professional, or the reaction sample is prepared in a PCR device, which requires the PCR device to specially set a container for carrying and preparing the reagent required for PCR amplification, resulting in a complex structure of the PCR device. In addition, there is a gap between the carrier and the heater, and between the inner wall of the carrier and the reaction sample, which results in low heat conduction efficiency, slow temperature rising and falling speed, and low PCR amplification efficiency. SUMMARY

[0005] One object of the present application is to provide a carrier to solve one of the above technical problems.

[0006] To achieve the above object, the first aspect of the present application provides a carrier, comprising a first wall and a second wall arranged oppositely, and a side wall arranged between the first wall and the second wall, the first wall, the second wall and the side wall form a sample containing cavity, the sample containing cavity is a flat structure, and at least part of the side wall is light-transmitting.

[0007] Optionally, the first wall and / or the second wall are made of a film of heat-conducting material.

[0008] Optionally, the first wall and / or the second wall are a heater, and the heater is used to heat the reaction sample in the sample containing cavity.

[0009] Optionally, the carrier is a flat structure.

[0010] Optionally, the carrier further comprises an extrusion cavity which deforms under external force to deform the sample containing cavity.

[0011] Optionally, the carrier comprises an extrusion region and an amplification region, the extrusion cavity is arranged in the extrusion region, and the sample containing cavity is arranged in the amplification region.

[0012] Optionally, the first wall and the second wall corresponding to the extrusion region are formed of deformable material.

[0013] Optionally, the extrusion cavity and the sample containing cavity are in communication, or the extrusion cavity and the sample containing cavity are separated by an elastic membrane.

[0014] Optionally, the extrusion region has an air inlet, and the air inlet is provided with an air inlet part for controlling the entry of gas into the extrusion cavity.

[0015] Optionally, the first wall and the second wall are made of aluminum film, or the first wall and the second wall are made of aluminum film and a separation film, and the separation film is connected to one side of the aluminum film close to the sample containing cavity.

[0016] Optionally, the carrier further comprises a first liquid inlet and a first exhaust hole in communication with the sample containing cavity.

[0017] Optionally, the first liquid inlet, the extrusion cavity, the sample containing cavity and the first exhaust hole are in communication through a first channel in sequence.

[0018] Optionally, the extrusion cavity, the first liquid inlet and the first exhaust hole are all arranged on the same side of the sample containing cavity.

[0019] Optionally, the extrusion cavity and the first liquid inlet are located directly above the sample containing cavity, the first exhaust hole is located above the side of the sample containing cavity, one end of the first channel is connected to the lower end of the sample containing cavity, and the other end is connected to the first exhaust hole; or

[0020] The first exhaust hole is located directly above the sample containing cavity, the extrusion cavity and the first liquid inlet are located above the side of the sample containing cavity, one end of the first channel is connected to the lower end of the sample containing cavity, and the other end is connected to the extrusion cavity.

[0021] Optionally, the first liquid inlet and the extrusion cavity are arranged on one side of the sample containing cavity, and the first exhaust hole is arranged on the other side of the sample containing cavity, and the one side of the sample containing cavity and the other side of the sample containing cavity are opposite.

[0022] Optionally, the carrier further comprises a second liquid inlet and a second air outlet communicating with the sample accommodating cavity, and the second liquid inlet, the sample accommodating cavity and the second air outlet communicate in sequence through a second channel.

[0023] Optionally, the second liquid inlet and the second air outlet are located on the same side of the sample accommodating cavity, or on opposite sides of the sample accommodating cavity.

[0024] Optionally, the liquid inlet and / or the air outlet are sealed by a sealing cover, a thermoplastic sealing piece, a pressure-sensitive adhesive or a plug, or the air outlet is provided with a breathable water-impermeable film.

[0025] Optionally, the carrier further comprises a liquid discharge part, and the liquid discharge part comprises a liquid discharge cavity, and the reaction sample in the sample accommodating cavity can be transferred to the liquid discharge cavity.

[0026] Optionally, a one-way valve, a two-way valve or a diaphragm is arranged between the liquid discharge cavity and the sample accommodating cavity.

[0027] Optionally, the first wall and the second wall are made of a deformable material.

[0028] Optionally, the heater comprises a heating piece, and the number of the heating piece is at least one.

[0029] Optionally, the number of the heating piece is at least two, and the at least two heating pieces are independent of each other.

[0030] Optionally, the carrier further comprises a temperature detection unit for detecting the temperature of the carrier.

[0031] Optionally, the heater further comprises a temperature calibration part for embodying the temperature of the heating piece, and the temperature detection unit is used to detect the temperature of the temperature calibration part.

[0032] Optionally, the heater further comprises a rapid conduction part for conducting the heat of the heating piece to the temperature calibration part.

[0033] Optionally, the carrier can further comprise a second contact, and the second contact is used for the resistance detection piece to detect the resistance of the heating piece.

[0034] Optionally, the flat structure means that the size of the sample accommodating cavity or the carrier in the direction perpendicular to the thickness direction thereof is greater than the size in the thickness direction thereof.

[0035] Optionally, the ratio of the size of the sample accommodating cavity or the carrier in the direction perpendicular to the thickness direction thereof to the size in the thickness direction thereof is greater than 5:1.

[0036] Optionally, the ratio is 50:1~100:1.

[0037] Another object of the present application is to provide a kit to solve one of the above technical problems.

[0038] To achieve the above object, the second aspect of the present application adopts the following technical solution: a kit comprising a reagent carrying part and the carrier, wherein the reagent carrying part is used for carrying at least a reagent.

[0039] Optionally, the reagent carrying part and the carrier are in an integrated structure; or

[0040] the reagent carrying part and the carrier are in a split structure; or

[0041] the reagent carrying part and the carrier are detachably connected; or

[0042] the reagent carrying part and the carrier are connected, and the included angle between the reagent carrying part and the carrier is adjustable.

[0043] Optionally, the reagent carrying part comprises at least one pre-set reagent cavity.

[0044] Optionally, the reagent carrying part further comprises at least one sample injection cavity and / or at least one empty cavity.

[0045] Optionally, the thickness direction of the sample containing cavity or the carrier is parallel or perpendicular to the depth direction of the cavity of the reagent carrying part.

[0046] As can be seen from the above, the sample containing cavity of the present application is in a flat structure, which makes the thickness of the reaction sample in the sample containing cavity very thin, and the distance between the center of the reaction sample and the surface of the liquid is very small. When at least one of the first wall and the second wall is heated, the temperature of the reaction sample can reach uniformity in a very short time, the heat transfer efficiency is high, and the heating and cooling speed of the reaction sample and the detection efficiency are greatly improved. The inner diameter of the PCR tube is relatively large compared with the flat structure of the containing cavity, the distance between the center of the reaction sample and the surface of the liquid is very large, and the temperature of the reaction sample needs a long time to reach uniformity, the heating and cooling speed of the reaction sample is low, and the detection efficiency is low.

[0047] The kit comprises a reagent carrying part and the carrier, and the reagent carrying part is used for carrying at least a reagent, so that after the sample is collected, the reagent in the reagent carrying part can be directly used to configure the reaction sample, and the detection efficiency is improved. At the same time, the reagent in the reagent carrying part can be placed in a required actual amount, and can be operated without professional test personnel, which has universality. In addition, the PCR equipment does not need to be specially provided with a container for carrying reagents and configuring reagents, so as to simplify the structure of the PCR equipment. BRIEF DESCRIPTION OF DRAWINGS

[0048] Figure 1ais a structural schematic diagram of a first carrier provided by an embodiment of the present application;

[0049] Figure 1b is Figure 1a is a sectional view of the carrier at C-C in FIG. 1;

[0050] Figure 2 is Figure 1b is a sectional view of the carrier at D-D in FIG. 1;

[0051] Figure 3 is an exploded view of a second carrier, an external heater and a cooling mechanism provided by an embodiment of the present application;

[0052] Figure 4 is a structural schematic diagram of the internal structure of the second carrier, the external heater and the cooling mechanism provided by an embodiment of the present application;

[0053] Figure 5 is an exploded view of a third carrier and a cooling mechanism provided by an embodiment of the present application;

[0054] Figure 6 is Figure 5 is a structural schematic diagram of the internal structure of the carrier provided by an embodiment of the present application;

[0055] Figure 7 is a structural schematic diagram of a fourth carrier provided by an embodiment of the present application;

[0056] Figure 8a is a structural schematic diagram of another view of the fourth carrier provided by an embodiment of the present application;

[0057] Figure 8b is a structural schematic diagram of one of the carriers provided by an embodiment of the present application;

[0058] Figure 9a is a structural schematic diagram of a fifth carrier provided by an embodiment of the present application;

[0059] Figure 9b is Figure 9a is a structural schematic diagram of the extrusion cavity of the carrier provided by an embodiment of the present application when extruding a sample containing cavity;

[0060] Figure 10 is a structural schematic diagram of a sixth carrier provided by an embodiment of the present application;

[0061] Figure 11a is a structural schematic diagram of a seventh carrier provided by an embodiment of the present application;

[0062] Figure 11b is a structural schematic diagram of an eighth carrier provided by an embodiment of the present application;

[0063] Figure 12 is a structural schematic diagram of a ninth carrier provided by an embodiment of the present application;

[0064] Figure 13 is a structural schematic diagram of the tenth carrier provided by the embodiment of the present application;

[0065] Figure 14 is a structural schematic diagram of the first kit provided by the embodiment of the present application;

[0066] Figure 15 is a schematic diagram of a reaction sample configuration process provided by the embodiment of the present application;

[0067] Figure 16 is a structural schematic diagram of the first kit when inserted into an external heater or cooling mechanism provided by the embodiment of the present application;

[0068] Figure 17 is a structural schematic diagram of the first kit when inserted into an external heater or cooling mechanism after being bent provided by the embodiment of the present application;

[0069] Figure 18 is a structural schematic diagram of the second kit when inserted into an external heater or cooling mechanism provided by the embodiment of the present application;

[0070] Figure 19a is a structural schematic diagram of the carrier including two heaters provided by the embodiment of the present application;

[0071] Figure 19b is a curve diagram of temperature calibration provided by the embodiment of the present application;

[0072] Figure 19c is a structural schematic diagram of the outer surface of the carrier provided by the embodiment of the present application;

[0073] Figure 20a is a structural schematic diagram of the eleventh carrier in an empty state provided by the embodiment of the present application;

[0074] Figure 20b is a structural schematic diagram of the carrier in Figure 20a in a full state provided by the embodiment of the present application;

[0075] Figure 21 is a schematic diagram of the carrier in Figure 20b in a pressure relief state provided by the embodiment of the present application;

[0076] Figure 22 is a schematic diagram of the carrier in Figure 21 when the external heater leaves the carrier provided by the embodiment of the present application.

[0077] in the figure:

[0078] 3, reagent carrying part; 31, preset reagent cavity; 32, sample cavity; 33, cavity; 34, sealing film;

[0079] 4, carrier; 41, sample accommodating cavity; 411, first side; 412, second side; 42, side wall; 43, first wall; 44, second wall; 45, heater; 451, heating element; 46, extrusion cavity; 47, extrusion zone; 48, amplification zone; 49, elastic membrane; 401, first liquid inlet; 402, first exhaust hole; 403, first channel; 404, second liquid inlet; 405, second exhaust hole; 406, second channel; 407, sealing cover; 409, membrane; 410, liquid discharge cavity;

[0080] 92, upper conducting assembly; 921, uniform heating layer; 93, temperature calibration part; 94, rapid conducting part; 941, patch; 942, guide column; 95, lower conducting assembly; 951, insulating thermal resistance layer; 952, thermal conducting layer; 96, second contact; 97, external electrical connection contact; 98, electrical connection lead;

[0081] 99, temperature detection unit;

[0082] 100, kit;

[0083] 200, external heater; 201, cooling mechanism; 203, detection unit; 204, pipette; 205, blow-off element. DETAILED DESCRIPTION

[0084] The technical solutions of the present application will be further described below in combination with the drawings and through specific embodiments. It can be understood that the specific embodiments described herein are only used to explain the present application, but not to limit the present application. In addition, it should be noted that only the parts related to the present application are shown in the drawings for the convenience of description, but not all.

[0085] In the present application, some orientation words are defined, and the orientation words such as "upper", "lower", "left", "right", "inner", "outer" are used for the convenience of understanding, and thus do not constitute a limitation on the protection scope of the present application.

[0086] In the present application, unless otherwise explicitly specified and limited, "on" or "under" of the first feature to the second feature can include that the first and second features are in direct contact, or that the first and second features are not in direct contact but are in contact through another feature between them. Moreover, "on", "above" and "on" of the first feature to the second feature include that the first feature is directly above and obliquely above the second feature, or only indicates that the horizontal height of the first feature is higher than that of the second feature. "Under", "below" and "under" of the first feature to the second feature include that the first feature is directly below and obliquely below the second feature, or only indicates that the horizontal height of the first feature is less than that of the second feature.

[0087] 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.

[0088] Example 1

[0089] This embodiment provides a vector 4 for use in PCR sampling, amplification, and / or detection, but is not limited thereto. The vector 4 can be a consumable, i.e., for single use only.

[0090] like Figures 1a-2 As shown, the carrier 4 provided in this embodiment includes a first wall 43 and a second wall 44 disposed opposite to each other, and a sidewall 42 disposed between the first wall 43 and the second wall 44. The first wall 43, the second wall 44, and the sidewall 42 form a sample receiving cavity 41. The sample receiving cavity 41 has a flat structure, and at least part of the sidewall 42 is light-transmitting. In particular, fluorescence can pass through the light-transmitting sidewall 42 of the sample receiving cavity 41. As an example, the sidewall 42 can be made of dimethylsiloxane (i.e., PDMS), polypropylene (i.e., PP), plexiglass (i.e., PMMA), or polycarbonate (i.e., PC). PMMA, PDMS, PP, and PC are optically transparent materials with good biocompatibility, thus meeting the requirements for fluorescence detection and having no impact on the reaction sample. As an example, the sample receiving cavity 41 is an amplification cavity used in a PCR reaction.

[0091] Optionally, the sidewalls 42 are all translucent and can be a one-piece structure for ease of processing. It is understood that the sidewalls 42 are annular structures, meaning continuously extending and closed structures. Annular structures are not limited to circular rings; they can also be rectangular or other polygonal rings, elliptical rings, or irregular rings, as long as the sidewalls 42 can enclose a space. Optionally, the sidewalls 42 are injection molded, such as directly injection molded into annular sidewalls 42, or a through hole is formed on a translucent plate using laser or other means. Then, the first wall 43 and the second wall 44 are connected to the opposite sides of the sidewalls 42 through a film-applying process such as adhesive bonding or welding, thereby forming the sample receiving cavity 41.

[0092] The sample accommodating cavity 41 is flat, which makes the reaction sample in the sample accommodating cavity 41 thin, the center of the reaction sample is far from the surface of the liquid, and the temperature of the reaction sample can reach uniformity in a short time when at least one of the first wall 43 and the second wall 44 is heated, the heat transfer efficiency is high, and the temperature rising and falling speed of the reaction sample and the detection efficiency are greatly improved. The inner diameter of the PCR tube is relatively large compared with the flat structure of the accommodating cavity, the center of the reaction sample is far from the surface of the liquid, and the temperature of the reaction sample needs a long time to reach uniformity, the temperature rising and falling speed of the reaction sample is low, and the detection efficiency is low.

[0093] As shown in Figures 3-6 At least part of the side wall 42 of the sample accommodating cavity 41 is transparent to light, and the detection unit 203 for detecting the fluorescence signal excited by the reaction sample in the sample accommodating cavity 41 can be detected through the transparent side wall 42, especially when neither the first wall 43 nor the second wall 44 is transparent to light, such as when the first wall 43 and the second wall 44 are both heaters 45 for heating the reaction sample or when the first wall 43 and the second wall 44 are heated by the external heater 200.

[0094] In an optional embodiment, the carrier 4 is flat, and the structure of the carrier 4 is consistent with the structure of the sample accommodating cavity 41, so that the first wall 43 and the second wall 44 can be thin. Compared with the method of forming a sample accommodating area by grooving on a bottom plate, the carrier 4 and the reaction sample in it can rise and fall faster because there is no need to heat a thick bottom plate.

[0095] It can be understood that the flat structure means that the thickness direction (i.e. the direction in which the first wall 43 and the second wall 44 are arranged) of the carrier 4 or the sample accommodating cavity 41 is smaller than the direction perpendicular to the thickness direction, for example, the ratio of the size of the direction perpendicular to the thickness direction to the size of the thickness direction is greater than 5:1. More preferably, the size of the thickness direction of the carrier 4 or the sample accommodating cavity 41 is much smaller than the size of the direction perpendicular to the thickness direction, for example, the ratio of the size to the size is 50:1 to 100:1, for example, the ratio of the size to the size is 90:1. For example, the sample accommodating cavity 41 is a cuboid, and the length and thickness of the cuboid can be greater than 5:1, for example, 90:1, for example, the thickness of the sample accommodating cavity 41 can be 0.3-1.0mm, and the width and length of the sample accommodating cavity 41 are about 10mm and 20mm respectively. For example, the sample accommodating cavity 41 can also be a cylindrical structure, and the ratio of the diameter to the thickness is greater than 5:1, for example, the thickness is 0.3-1.0mm, and the diameter is 5-20mm. Of course, the cross section of the sample accommodating cavity 41 can be polygonal or elliptical.

[0096] Optionally, the first wall 43 and / or the second wall 44 are membranes 409 made of thermally conductive material. In particular, the side of the carrier 4 heated by the external heater 200 is a membrane 409 made of thermally conductive material. Specifically, membrane 409 is an aluminum membrane and a separator membrane. Optionally, the separator membrane is a polypropylene membrane (i.e., PP membrane). The separator membrane is in direct contact with the reaction solution, which can prevent the aluminum membrane from affecting the reaction sample. The thickness of the aluminum membrane can be tens of μm, such as 30 μm, 60 μm, etc. An aluminum membrane of this thickness can be deformable and has a certain strength. The thickness of the separator membrane can be 10-30 μm, such as 20 μm, etc. The separator membrane only needs to be able to separate the reaction sample from the aluminum membrane. Of course, membrane 409 can also be an aluminum membrane without a PP membrane. The thickness of the aluminum membrane can be tens of μm, such as 30 μm, 60 μm, etc. An aluminum membrane of this thickness can be deformable and has a certain strength. In particular, the side of the carrier 4 heated by the external heater 200 is a membrane 409 made of thermally conductive material.

[0097] like Figure 3 and Figure 4 As shown, in an optional embodiment, the first wall 43 and the second wall 44 of the carrier 4 are both films 409 made of thermally conductive material. Specifically, when the first wall 43 and the second wall 44 are heated by the external heater 200, the first wall 43 and the second wall 44 of the carrier 4 can quickly transfer the heat from the external heater 200 to the reaction sample in the sample receiving cavity 41. At this time, rapid heating and cooling are achieved through double-sided heating, and the detection unit 203 performs fluorescence detection on the side of the carrier 4. While achieving rapid heating and cooling and fluorescence detection, compared with fluorescence detection through the first wall 43 or the second wall 44, the device structure is more compact and the detection efficiency is further improved. At the same time, the flat structure of the first wall 43 and the second wall 44 of the carrier 4 can increase the contact area between the carrier 4 and the external heater 200, thereby further accelerating the heating and cooling rate.

[0098] like Figure 5 and Figure 6 As shown, the carrier 4 includes at least one heater 45, with the first wall 43 and / or the second wall 44 serving as the heater 45. The heater 45 is used to heat the reaction sample within the sample receiving cavity 41, thus eliminating the need for external heater 200 to heat the reaction sample. That is, as... Figure 5 As shown, both the first wall 43 and the second wall 44 are heaters 45, and the heaters 45 are in direct contact with the reaction sample inside the carrier 4. When both the first wall 43 and the second wall 44 are heaters 45, the heating rate of the reaction sample is further increased. At the same time, the detection unit 203 performs detection from the side, especially from both sides or more sides.

[0099] At this time, the heater 45 is a part of the carrier 4, that is, the carrier 4 is an integral structure with the heater 45, and the heater 45 and the sample containing cavity 41 do not have an air layer, thereby accelerating the heat transfer speed of the heater 45 and the reaction sample in the sample containing cavity 41, and further accelerating the nucleic acid amplification process and improving the detection efficiency. The reaction sample is in direct contact with the heater 45, and at the same time, the flat structure of the carrier 4 has a large contact area with the heater 45, so that the temperature rising and falling speed of the reaction sample is faster.

[0100] As shown in Figure 7 and Figure 8a , in an alternative embodiment, especially when the carrier 4 does not include the heater 45, the carrier 4 further includes a pressing cavity 46, which deforms under an external force F to deform the sample containing cavity 41, and further make the pressing cavity 46 control the pressure in the sample containing cavity 41. Specifically, the pressing cavity 46 is in communication with the sample containing cavity 41 through the first channel 403.

[0101] As in the PCR amplification, the pressing cavity 46 is pressed, and the gas and / or liquid (the liquid can be the reaction sample) in the pressing cavity 46 pressurizes the reaction sample in the sample containing cavity 41, and further the reaction sample presses the corresponding first wall 43 and second wall 44 of the sample containing cavity 41, so that the corresponding first wall 43 and second wall 44 of the sample containing cavity 41 expand outward, and when the outside of the corresponding first wall 43 and second wall 44 of the sample containing cavity 41 is provided with an external heater 200, the corresponding first wall 43 and second wall 44 of the sample containing cavity 41 are further attached to the external heater 200. At the same time, the reaction sample is attached to the inside of the corresponding first wall 43 and second wall 44 of the sample containing cavity 41 under the pressure of the pressing cavity 46, and since the outside of the corresponding first wall 43 and second wall 44 of the sample containing cavity 41 is attached to the external heater 200, the heat conduction efficiency can be greatly improved. In this embodiment, the pressing cavity 46 is filled with air or other gas, and the heat conductivity of the gas is lower than that of the liquid, and the gas has a heat insulation effect. During the nucleic acid amplification stage, the reaction sample is repeatedly heated and cooled, at this time, the heat exchange between the reaction sample and the gas in the pressing cavity 46 is small, which is beneficial to the uniform temperature of the reaction sample and the realization of rapid temperature rising and falling. At the same time, when the pressing cavity 46 is filled with air or other gas, there is no need to inject more liquid into the carrier 4, so that the temperature rising and falling speed will not be slowed down due to the need to raise and lower the temperature of the excess liquid.

[0102] Continuing as shown in Figure 7 and Figure 8a , the carrier 4 includes a pressing area 47 and an amplification area 48, the pressing cavity 46 is arranged in the pressing area 47, and the sample containing cavity 41 is arranged in the amplification area 48. The pressing cavity 46 can be deformed by pressing the pressing area 47, the amplification area 48 is deformed, the cavity wall of the amplification area 48 is deformed, and is attached to the external heater 200. AsFigure 8a As shown, the extrusion cavity 46 can be extruded by extruding the first wall 43 and the second wall 44 at the same time, of course, as shown in other optional embodiments, the extrusion cavity 46 can also be extruded by extruding one of the first wall 43 and the second wall 44, and placing the other one of the first wall 43 and the second wall 44 on a plane. Figure 8b As shown, the extrusion cavity 46 can be extruded by extruding the first wall 43 and the second wall 44 at the same time, of course, as shown in other optional embodiments, the extrusion cavity 46 can also be extruded by extruding one of the first wall 43 and the second wall 44, and placing the other one of the first wall 43 and the second wall 44 on a plane.

[0103] As shown, the first wall 43 and the second wall 44 corresponding to the amplification area 48 are further optionally made of a film 409 of a thermally conductive material (for example, aluminum film or aluminum film and pp film), and the first wall 43 and the second wall 44 corresponding to the amplification area 48 are further optionally made of a film 409 of a thermally conductive material (for example, aluminum film or aluminum film and pp film). Figure 7 As shown, the first wall 43 and the second wall 44 corresponding to the amplification area 48 are further optionally made of a film 409 of a thermally conductive material (for example, aluminum film or aluminum film and pp film), and the first wall 43 and the second wall 44 corresponding to the amplification area 48 are further optionally made of a film 409 of a thermally conductive material (for example, aluminum film or aluminum film and pp film). Figure 7 As shown, the first wall 43 and the second wall 44 corresponding to the amplification area 48 are further optionally made of a film 409 of a thermally conductive material (for example, aluminum film or aluminum film and pp film), and the first wall 43 and the second wall 44 corresponding to the amplification area 48 are further optionally made of a film 409 of a thermally conductive material (for example, aluminum film or aluminum film and pp film).

[0104] As shown, the first wall 43 and the second wall 44 corresponding to the amplification area 48 are further optionally made of a film 409 of a thermally conductive material (for example, aluminum film or aluminum film and pp film), and the first wall 43 and the second wall 44 corresponding to the amplification area 48 are further optionally made of a film 409 of a thermally conductive material (for example, aluminum film or aluminum film and pp film). Figure 7 Figure 8a As shown, the first wall 43 and the second wall 44 corresponding to the amplification area 48 are further optionally made of a film 409 of a thermally conductive material (for example, aluminum film or aluminum film and pp film), and the first wall 43 and the second wall 44 corresponding to the amplification area 48 are further optionally made of a film 409 of a thermally conductive material (for example, aluminum film or aluminum film and pp film).

[0105] As shown, the first wall 43 and the second wall 44 corresponding to the amplification area 48 are further optionally made of a film 409 of a thermally conductive material (for example, aluminum film or aluminum film and pp film), and the first wall 43 and the second wall 44 corresponding to the amplification area 48 are further optionally made of a film 409 of a thermally conductive material (for example, aluminum film or aluminum film and pp film). Figure 7 Figure 8a As shown, the first wall 43 and the second wall 44 corresponding to the amplification area 48 are further optionally made of a film 409 of a thermally conductive material (for example, aluminum film or aluminum film and pp film), and the first wall 43 and the second wall 44 corresponding to the amplification area 48 are further optionally made of a film 409 of a thermally conductive material (for example, aluminum film or aluminum film and pp film).

[0106] As shown, the first wall 43 and the second wall 44 corresponding to the amplification area 48 are further optionally made of a film 409 of a thermally conductive material (for example, aluminum film or aluminum film and pp film), and the first wall 43 and the second wall 44 corresponding to the amplification area 48 are further optionally made of a film 409 of a thermally conductive material (for example, aluminum film or aluminum film and pp film). Figure 7 Figure 8a Figure 8b Figure 10 As shown, the first wall 43 and the second wall 44 corresponding to the amplification area 48 are further optionally made of a film 409 of a thermally conductive material (for example, aluminum film or aluminum film and pp film), and the first wall 43 and the second wall 44 corresponding to the amplification area 48 are further optionally made of a film 409 of a thermally conductive material (for example, aluminum film or aluminum film and pp film). Figure 8a Figure 8b ​​​​​​As shown, the first liquid inlet 401 and the first gas outlet hole 402 can also penetrate the side wall 42 of the carrier 4, i.e. the first liquid inlet 401 and the first gas outlet hole 402 are located on the side wall 42.

[0107] The reaction sample first enters the extrusion cavity 46 from the first liquid inlet 401, and then enters the amplification area 48 from the extrusion cavity 46. In addition, before the first gas outlet hole 402 is sealed, the extrusion cavity 46 can be slightly extruded to ensure that the gas in the sample containing cavity 41 is extruded to the first gas outlet hole 402, thereby ensuring that the sample containing cavity 41 is filled with reaction sample, so as to ensure that there is no or very few bubbles in the amplification area 48. It can be understood that, since the thickness of the sample containing cavity 41 in the embodiment is very thin, if there is a bubble in the sample containing cavity 41 when the fluorescent detection device detects fluorescence through the side wall 42 of the sample containing cavity 41, the result of the fluorescent detection will be affected. Among them, as long as the bubble avoids the light part of the fluorescent detection device, when the carrier 4 is placed vertically (i.e. the direction shown by the arrow L in Figure 10 is upward), the bubble can accumulate at a position where the light part does not pass through the upper end of the carrier 4. In addition, one of the reasons for setting the sample containing cavity 41 as a flat structure is to realize rapid temperature rise and fall of the reaction sample. If there is a bubble, especially a bubble layer, in the sample containing cavity 41, the heat conduction efficiency in the bubble will be greatly reduced, which will affect the temperature rise and fall speed and the temperature uniformity of the reaction sample. Therefore, the first gas outlet hole 402 in the embodiment can discharge the bubbles in the amplification area 48, and the absence or presence of very few bubbles in the amplification area 48 can ensure the accuracy of the fluorescent detection result, the temperature uniformity of the reaction sample, and the amplification efficiency. Another reason for setting the sample containing cavity 41 as a flat structure is that the liquid thermal convection when the carrier 4 is placed vertically (i.e. the direction shown by the arrow L in Figure 10 is upward) is beneficial to further mixing the liquid and discharging the bubbles.

[0108] As shown in Figure 7 and Figure 10 , the first liquid inlet 401 and the extrusion cavity 46 are arranged on one side of the sample containing cavity 41, the first gas outlet hole 402 is arranged on the other side of the sample containing cavity 41, and the one side of the sample containing cavity 41 and the other side of the sample containing cavity 41 are opposite. When the reaction sample is added into the sample containing cavity 41 from the first liquid inlet 401, the reaction sample first passes through the extrusion cavity 46, and then flows into the sample containing cavity 41, and the gas in the sample containing cavity 41 can be discharged from the first gas outlet hole 402.

[0109] As shown in Figure 9a, of course, in other alternative embodiments, the outer wall of the extrusion cavity 46 can also not be the first wall 43 and the second wall 44, but the extrusion area 47 comprises an elastic film 49, which surrounds the extrusion cavity 46. In this embodiment, the elastic film 49 is a film that can restore its original shape after deformation. The material forming the elastic film 49 can have a greater deformation capacity than the material forming the first wall 43 and the second wall 44, and the material forming the elastic film 49 has elasticity and can restore its original shape. For example, the elastic film 49 is made of polydimethylsiloxane (i.e. PDMS) material, so that the extrusion area 47 is more easily deformed. The elastic film 49 forms the extrusion cavity 46, which can achieve repeated extrusion of the extrusion cavity 46, so that the reaction sample in the sample containing cavity 41 can form a flocculation flow, thereby mixing the reaction sample and improving the temperature uniformity of the reaction sample. In addition, when the first wall 43 and the second wall 44 are aluminum films or aluminum films and pp films, and the corresponding cavity wall at the extrusion cavity 46 is the elastic film 49, the aluminum film is not easy to restore after being outwardly protruded. If the extrusion cavity 46 is repeatedly extruded, the aluminum film corresponding to the sample containing cavity 41 will be protruded during the first extrusion, and the aluminum film corresponding to the sample containing cavity 41 will not restore its shape after the extrusion cavity 46 is released. Therefore, after the extrusion cavity 46 is released, there will be a small gap between the reaction sample and the aluminum film. Therefore, if the extrusion cavity 46 is repeatedly extruded during the amplification process, the liquid in the sample containing cavity 41 will form a flocculation flow, thereby mixing the liquid uniformly and improving the amplification efficiency.

[0110] As Figure 9a In other embodiments, the extrusion cavity 46 and the sample containing cavity 41 are not connected, but the extrusion cavity 46 and the sample containing cavity 41 are separated by the elastic film 49, thereby preventing the gas or / and solution in the extrusion cavity 46 from contaminating the sample containing cavity 41. In addition, it can also avoid the gas in the extrusion cavity 46 entering the sample containing cavity 41, thereby avoiding the formation of bubbles in the sample containing cavity 41, which affects the heat conduction between the heater and the reaction sample and affects the detection of the reaction sample. At the same time, repeated extrusion of the extrusion cavity 46 can cause the sample in the sample containing cavity 41 to form a turbulent flow, thereby mixing the reaction sample and improving the temperature uniformity of the reaction sample.

[0111] At this time, the first liquid inlet 401, the sample containing cavity 41 and the first exhaust hole 402 are sequentially connected through the first channel 403.

[0112] As Figure 9bAs shown, the pressing cavity 46 has gas and / or solution, the pressing cavity 46 is pressed, the elastic membrane 49 adjacent to the amplification area 48 expands to the side where the amplification area 48 is located, and then the elastic membrane 49 presses the reaction sample in the sample containing cavity 41. The elastic membrane 49 can be made of pp film, and of course the elastic membrane 49 can also be made of other materials, such as rubber, PDMS, etc. Preferably, the pressing cavity 46 stores air or other gas, the thermal conductivity of the gas is low relative to the liquid, and the gas has a heat insulation effect. During the nucleic acid amplification stage, the reaction sample is repeatedly heated and cooled, at this time, the reaction sample exchanges less heat with the gas in the pressing cavity 46, which is beneficial to the uniform temperature of the reaction sample and the realization of rapid temperature rise and fall. At the same time, when the pressing cavity 46 stores air or other gas, there is no need to inject more liquid into the carrier 4, so that the temperature rise and fall speed will not be slowed down because of the need to raise and lower the temperature of the excess liquid.

[0113] In still another optional embodiment, in order to enable the pressing cavity 46 to control the pressure of the sample containing cavity 41, the pressing cavity 46 and the sample containing cavity 41 are communicated, the pressing area 47 has a gas inlet, and the gas inlet is provided with a gas inlet part (not shown in the figure) for controlling the gas entering the pressing cavity 46. For example, the gas inlet part is a gas-permeable water-impermeable film which is provided on the gas inlet as a cover, and the gas-permeable water-impermeable film can allow the gas to pass through but not the liquid. During PCR amplification, the gas is introduced into the pressing cavity 46 through the gas-permeable water-impermeable film to control the pressure of the pressing cavity 46, and then the pressing cavity 46 exerts pressure on the reaction sample in the sample containing cavity 41. The gas inlet part is a one-way valve, which is opened under pressure when the gas inlet is ventilated by a pump or other gas filling equipment, and then the gas enters the pressing cavity 46 to control the pressure of the pressing cavity 46, and then the pressing cavity 46 exerts pressure on the reaction sample in the sample containing cavity 41.

[0114] More embodiments of the liquid inlet, gas outlet and channel will be introduced below, such as Figure 11a and Figure 11b As shown, the pressing cavity 46, the first liquid inlet 401 and the first gas outlet 402 are all arranged on the same side of the sample containing cavity 41. When the reaction sample is added into the sample containing cavity 41, the gas in the amplification area 48 can be discharged through the first gas outlet 402, and at the same time, when the PCR amplification and / or detection is carried out, the carrier 4 is placed vertically, Figure 11a the direction of the arrow L in the figure is upward, and when the reaction sample is added into the sample containing cavity 41, the gas in the amplification area 48 can be pressed to be discharged through the first gas outlet 402.

[0115] Optionally, as shown in Figure 11aAs shown, the pressing cavity 46 and the first liquid inlet 401 are located above the sample containing cavity 41, the first exhaust hole 402 is located above the side of the sample containing cavity 41, and one end of a first channel 403 is connected to the lower end of the sample containing cavity 41 and the other end is connected to the first exhaust hole 402. When the reaction sample is added into the sample containing cavity 41, the gas in the amplification zone 48 can be exhausted through the first exhaust hole 402 or the pressing cavity 46.

[0116] More preferably, as shown in the figures, Figure 11b As shown, the first exhaust hole 402 is located above the sample containing cavity 41, the pressing cavity 46 and the first liquid inlet 401 are located above the side of the sample containing cavity 41, and one end of a first channel 403 is connected to the lower end of the sample containing cavity 41 and the other end is connected to the pressing cavity 46. It can be understood that the sample containing cavity 41 has a first side 411 and a second side 412 opposite to each other, and when the carrier 4 is used, the first side 411 is located above the second side 412, the first exhaust hole 402 is located above the first side 411, and the pressing cavity 46 and the first liquid inlet 401 are located above the side of the first side 411. One end of a first channel 403 is connected to the second side 412 of the sample containing cavity 41 and the other end is connected to the pressing cavity 46, and one end of another first channel 403 is connected to the first exhaust hole 402 and the other end is connected to the first side 411 of the sample containing cavity 41. On the one hand, when the liquid is added into the sample containing cavity 41, the air floats up and is more easily exhausted through the first exhaust hole 402; on the other hand, during the amplification stage, even if the pressing cavity 46 is not filled with the reaction sample, when the pressing cavity 46 is pressed, the reaction sample in the first channel 403 enters the sample containing cavity 41, thereby preventing the air in the pressing cavity 46 from entering the sample containing cavity 41 and ensuring that the reaction sample in the sample containing cavity 41 is not contaminated; on the other hand, the gas generated during the heating process of the reaction sample in the sample containing cavity 41 during the amplification stage is more easily floated up to the first exhaust hole 402, and when the end surface of the first exhaust hole 402 is covered with a breathable and water-impermeable film, the gas can also be exhausted.

[0117] The first exhaust hole 402 is located above to facilitate the air bubbles in the sample containing cavity 41 to float up to the first exhaust hole 402, thereby avoiding the air bubbles from appearing at the side of the amplification zone 48 close to the first wall 43 and the second wall 44, and further ensuring the accuracy of the detection by the detection unit 203.

[0118] As shown in the figures, Figure 12 and 13As shown, when the carrier 4 does not include the extrusion chamber 46, the carrier 4 also includes a second liquid inlet 404 and a second vent 405 communicating with the sample receiving chamber 41. The reaction sample enters the sample receiving chamber 41 through the second liquid inlet 404, and the gas in the sample receiving chamber 41 is discharged through the second vent 405. Specifically, the second liquid inlet 404, the sample receiving chamber 41, and the second vent 405 are connected sequentially through a second channel 406. In this case, the first wall 43 and the second wall 44 of the carrier 4 can both be heaters 45 for heating the reaction sample, or both can be membranes 409 made of thermally conductive material.

[0119] like Figure 12 As shown, the second liquid inlet 404 and the second vent 405 are located on opposite sides of the sample receiving cavity 41. When a reaction sample is added to the sample receiving cavity 41, gas in the amplification zone 48 can be discharged through the second vent 405. Optionally, the second liquid inlet 404 and the second vent 405 can be provided at, for example... Figure 12 On the first wall 43 or the second wall 44 shown, of course, as Figure 11b As shown, the second liquid inlet 404 and the second vent hole 405 can also penetrate the side wall 42 of the carrier 4, that is, the second liquid inlet 404 and the second vent hole 405 are located on the side wall 42.

[0120] like Figure 13 As shown, the second inlet 404 and the second vent 405 are located on the same side of the sample receiving cavity 41. When the reaction sample is added into the sample receiving cavity 41, the gas in the amplification region 48 can be discharged through the second vent 405. Simultaneously, during PCR amplification and / or detection, the carrier 4 is placed vertically, i.e., as shown... Figure 13 The direction indicated by the middle arrow L is upward, and the second vent 405 is located at the top, so that the air bubbles in the sample receiving cavity 41 can float to the second vent 405, avoiding the appearance of air bubbles on the side of the amplification area 48 near the first wall 43 and the second wall 44, thereby ensuring the accuracy of the detection unit 203.

[0121] like Figure 7 As shown, the inlet and / or vent can be sealed with a sealing cap 407, which can be integrated with the carrier 4. Alternatively, the inlet and / or vent can be sealed with a thermoplastic sealant, pressure-sensitive adhesive, or a stopper. Sealing the inlet and vent with the sealing cap 407 before amplification prevents evaporation and contamination of the reaction sample, while also maintaining a certain pressure within the sample chamber 41. Furthermore, a breathable but waterproof membrane can be installed on the vent, allowing the reaction sample to be discharged through the vent, while also venting gas from the sample chamber 41.

[0122] like Figure 14As shown, this embodiment also provides a reagent kit 100, including a reagent carrier 3 and the aforementioned carrier 4. The reagent carrier 3 is used to carry reagents. Therefore, after sample collection, the reagents in the reagent carrier 3 can be directly used to prepare reaction samples, improving detection efficiency. Simultaneously, the reagents in the reagent carrier 3 can be quantitatively placed according to the required amount, eliminating the need for professional testing personnel and demonstrating universality. Furthermore, it eliminates the need for dedicated reagent carriers and reagent preparation containers in PCR equipment, thus simplifying the PCR equipment structure.

[0123] like Figure 14 As shown, the reagent carrier 3 may include at least one pre-placed reagent chamber 31, in which reagents are placed. The reagent carrier 3 may also include at least one injection chamber 32 and / or at least one cavity 33. The injection chamber 32 may hold a throat swab or liquid sample, and the cavity 33 may be used for mixing reagents. A total of five injection chambers 32, pre-placed reagent chambers 31, and cavities 33 may be provided; however, more or fewer than five may be provided as needed.

[0124] At least one sample inlet chamber 32, at least one pre-filled reagent chamber 31, and at least one empty chamber 33 are provided with openings for reagents or samples to enter or exit the chambers. A sealing film 34 is provided on the opening. Before using the reagent kit 100, the sealing film 34 is lifted to isolate the inside of the chamber from the outside, thus ensuring the cleanliness of the chamber.

[0125] A sealing film 34 covers the sample inlet chamber 32, the pre-prepared reagent chamber 31, and the empty chamber 33. During sampling, the sealing film 34 can be torn open manually or automatically. Alternatively, the sealing film 34 can be a separate structure; for example, a sealing film 34 can be placed at the opening of the sample inlet chamber 32. Before placing a throat swab or liquid sample, the user can manually or automatically remove the sealing film 34 and then place the sample into the sample inlet chamber 32. The sealing film 34 ensures that the sample inlet chamber 32 is not contaminated. Another sealing film 34 can cover the pre-prepared reagent chamber 31 and the empty chamber 33. When reagent preparation is needed, the sealing film 34 is removed manually or automatically, and the pipette 204 draws the reagent from the pre-prepared reagent chamber 31 and transfers it into the empty chamber 33 for reagent preparation, as well as transferring the reaction sample formed by the reagent and the sample into the carrier 4.

[0126] like Figure 15 The process of preparing reaction samples using kit 100 via manual or automated equipment is illustrated schematically. For example, the sample inlet chamber 32 is used to contain the sample processing solution, and two pre-filled reagent chambers 31 are provided, one for containing PCR reaction buffer and the other for containing the enzyme system.

[0127] Step 1: Tear open the sealing film 34;

[0128] Step 2, place the collected sample into the sample cavity 32;

[0129] Step 3, transfer the PCR reaction buffer in one of the preset reagent cavities 31 into the empty cavity 33;

[0130] Step 4, transfer the enzyme system in another preset reagent cavity 31 into the empty cavity 33;

[0131] Step 5, transfer the sample processing solution in the sample cavity 32 into the empty cavity 33;

[0132] Step 6, mix the reaction sample in the empty cavity 33 by the blowing piece 205;

[0133] Step 7, transfer the reaction sample in the empty cavity 33 into the carrier 4 by the pipette 204;

[0134] Step 8, seal the liquid inlet and the exhaust hole, and again set the sealing film 34 on the opening.

[0135] As shown in Figure 14 and 16 , the thickness direction of the sample containing cavity 41 or the carrier 4 (as shown by the arrow H) is parallel to the depth direction of the reagent cavity. The reagent carrying part 3 and the carrier 4 can be an integrated structure, and when nucleic acid amplification is performed, the carrier 4 is inserted between the two external heaters 200 or other amplification required structures (such as the cooling mechanism 201 for cooling the reaction sample) along the direction indicated by the arrow in the middle, and the thickness direction of the carrier 4 is consistent with the vertical direction, so that the opening of the cavity in the reagent carrying part 3 is upward, and when the sealing film 34 is not set on the opening, the residual solution in the cavity can still be prevented from falling and causing pollution. Figure 14 Figure 16 However, since the sample containing cavity 41 and / or the carrier 4 is a flat structure, the air bubbles often run through the thickness direction of the sample containing cavity 41, so that the air bubbles are easily arranged opposite to the detection unit 203 located on the side of the carrier 4, and then the detection result is inaccurate.

[0136] To avoid the above problems, optionally, the reagent carrying part 3 and the carrier 4 are a split structure, and then the carrier 4 can be inserted between the two external heaters 200 or other amplification required structures (for example, the cooling mechanism 201 for cooling the reaction sample as shown in ) according to the needs of the direction, such as the thickness direction of the carrier 4 (as shown by the arrow Y) is perpendicular to the vertical direction (as shown by the arrow Z, the three directions X, Y and Z are perpendicular to each other) (hereinafter referred to as the vertical insertion of the carrier 4) between the two external heaters 200 or other amplification required structures (such as the cooling mechanism 201 for cooling the reaction sample).

[0137] Figure 4 Figure 17 Figure 17 ​​​​

[0138] Alternatively, the reagent carrier 3 and the carrier 4 can be detachably connected. For example, the reagent carrier 3 and the carrier 4 can be separated from each other at the connection point. Furthermore, multiple spaced holes can be provided between the connection point of the carrier 4 and the reagent carrier 3, allowing for easy breakage between the carrier 4 and the reagent carrier 3. After the carrier 4 is separated, it can be vertically inserted between two external heaters 200 or other structures required for amplification (such as a cooling mechanism 201 for cooling reaction samples).

[0139] Alternatively, the reagent carrier 3 is connected to the carrier 4, and the angle between the reagent carrier 3 and the carrier 4 is adjustable, such as allowing the carrier 4 and the reagent carrier 3 to be bent. If a groove is provided between the carrier 4 and the reagent carrier 3, the carrier 4 or the reagent carrier 3 can be bent along the groove. Figure 17 As shown, after the carrier 4 or reagent carrier 3 is bent, along... Figure 17 As indicated by the middle arrow, the carrier 4 is vertically inserted into two external heaters 200 or other structures required for amplification (such as a cooling mechanism 201 for cooling reaction samples), and when the carrier 4 is inserted, the opening of the reagent chamber faces upward, so that the reagent in the reagent chamber will not drip.

[0140] like Figure 18 As shown, preferably, the thickness direction of the sample receiving cavity 41 or the carrier 4 (e.g., ...) Figure 18 The X direction (as shown) and the depth direction of the reagent chamber (as shown) Figure 18 As shown, the Z direction (and the X, Y, and Z directions are mutually perpendicular) are perpendicular. Thus, when the carrier 4 and the reagent carrier 3 are an integral structure, and the relative positions between the carrier 4 and the reagent carrier 3 do not change, along... Figure 18 The direction indicated by the middle arrow also allows the carrier 4 to be vertically inserted into the two external heaters 200 or other structures required for amplification (such as the cooling mechanism 201 for cooling reaction samples). This ensures that the opening of the cavity in the reagent carrier 3 faces upwards, and that the air bubbles can also float to the top of the carrier 4.

[0141] like Figure 19a As shown, the heater 45 includes a heating element 451. A power supply is connected to the heating element 451, which is a controllable heating source inside the heater 45. It can be a resistor, such as a thin wire structure made of copper. The heating power is controlled by controlling the current flowing through the resistor, thereby achieving temperature control. In other optional embodiments, the heating element 451 can also be a coil structure or use ferromagnetic materials for electromagnetic induction heating.

[0142] like Figure 19aAs shown, preferably, the heater 45 comprises at least two independently controlled heating elements 451, which can be independently controlled to improve the uniformity of the reaction sample temperature. For example, if the temperature of one heating element 451 does not reach the preset temperature (how to detect the temperature of the heating element 451 will be described in detail below), the current of the heating element 451 is increased to quickly raise the reaction sample to the preset temperature. In the embodiment, since the heater 45 is in direct contact with the reaction sample in the carrier 4, the heat conduction efficiency between the heater 45 and the reaction sample is high, and the temperature of the heating element 451 of the heater 45 can be equivalent to the temperature of the reaction sample. Therefore, controlling the temperature of each heating element 451 to reach the preset temperature can make the reaction sample at each location be at the preset temperature, thereby ensuring the uniformity of the reaction sample temperature.

[0143] As shown in the figure, the heater 45 can further comprise an upper conducting assembly 92 and a lower conducting assembly 95, and the heating element 451 is clamped between the upper conducting assembly 92 and the lower conducting assembly 95. The upper conducting assembly 92 and the lower conducting assembly 95 have the functions of conducting heat and insulation. Figure 19a

[0144] The heater 45 comprises a uniform heating layer 921, and specifically, the upper conducting assembly 92 can further comprise the uniform heating layer 921. The uniform heating layer 921 is in direct contact with the reaction sample in the sample containing cavity 41, and the uniform heating layer 921 can ensure the uniform conduction of heat in the longitudinal and transverse directions (i.e. the thickness direction of the reaction sample and the direction perpendicular to the thickness direction), thereby ensuring the temperature uniformity of the sample liquid. Optionally, the uniform heating layer 921 is made of an insulating material, such as high thermal conductivity ceramic.

[0145] The uniform heating layer 921 is made of an insulating material, and the uniform heating layer 921 is adjacent to the heating element 451. At this time, the number of layers of the carrier 4 can be reduced, and the time for the heating element 451 to transfer heat to the reaction sample in the carrier 4 and the time required for the carrier 4 to dissipate heat can be shortened.

[0146] As shown in the figure, the lower conducting assembly 95 further comprises an insulating thermal resistance layer 951. The insulating thermal resistance layer 951 has certain thermal resistance and insulation properties. In addition to insulating the heating element 451, the insulating thermal resistance layer 951 can also form a longitudinal thermal resistance. The size of the thermal resistance can be designed by selecting the material and thickness, to meet different design requirements. For example, a thin layer with a thickness of 0.1-0.3mm can be used, and the material thermal conductivity is selected in the range of 0.2-0.5W / mK. Generally, the thermal resistance of this layer is much larger than that of other layers of the structure, so the insulating thermal resistance layer is the main source of thermal resistance for the carrier 4 to dissipate heat to the cooling mechanism 201. The insulating thermal resistance layer 951 is one of the main factors affecting the thermal performance of the carrier 4. Figure 19a

[0147] ​​Optionally, the lower conducting assembly 95 further comprises a heat conducting layer 952, which is located on the side of the insulating thermal resistance layer 951 away from the heating element 451. Further, the heat conducting layer 952 is the outermost layer of the lower conducting assembly 95, which directly contacts the cooling mechanism 201. The heat conducting layer 952 is made of metal such as copper or other material with high thermal conductivity. Due to cost control or processing technology limitations, etc., the surface of the lower conducting assembly 95 in contact with the cooling mechanism 201 inevitably has point contact. When the outermost layer of the lower conducting assembly 95 is the heat conducting layer 952, even if the heat conducting layer 952 has point contact with the cooling mechanism 201, the heat conducting layer 952 can evenly distribute heat throughout the heat conducting layer 952 due to its good conductivity, and thus evenly distribute heat to other layers of the lower conducting assembly 95.

[0148] Preferably, the heating element 451 of the present embodiment is a resistor, which has a specific relationship with its temperature, so that the real-time resistance change of the heating element 451 can be measured while heating, and the average temperature of the heating element 451 can be derived through the resistance temperature coefficient and the nominal resistance value. This temperature, which reflects the current temperature of the carrier 4 in real time without delay, can be used to quickly feedback control the temperature of the carrier 4 and the reaction sample, so that the sample temperature can be more accurately controlled and the overall reaction speed of the temperature control system can be improved compared with the prior art.

[0149] In order to detect the resistance of the heating element 451, the carrier 4 can also optionally comprise a second contact 96 for the resistance detection element to detect the resistance of the heating element 451 to measure the temperature of the heating element 451 by resistance temperature measurement method. The resistance detection element can include a terminal that contacts and electrically connects with the second contact 96, so that the voltage U and current I of the heating element 451 are detected through the second contact 96, and then the resistance R (R=U / I) is obtained.

[0150] However, the resistance temperature measurement method has the disadvantage that for the same type of resistor, such as copper wire resistor, the nominal resistance value and resistance temperature coefficient (the resistance value at the nominal temperature is referred to as the nominal resistance value, and the nominal resistance refers to the resistance value claimed (or marked) to be true at this temperature, which is the nominal temperature, and the nominal temperature can be arbitrarily selected according to requirements) are slightly different, which may cause a slight difference between the real resistance temperature coefficient and the nominal resistance value of a single heating element 451, which may cause temperature measurement error, therefore preferably, Figure 19aAs shown, the carrier 4 also comprises a temperature detection unit 99 for detecting the temperature of the carrier 4, which can comprise a contact temperature sensor. It can be understood that the contact temperature sensor is a sensor that needs to be in contact with the measured position of the carrier 4 when measuring the temperature. Although the temperature detection unit 99 can detect the temperature of the carrier 4, since the temperature of the reaction sample changes rapidly during the amplification stage, when the temperature detection unit 99 detects the temperature of the carrier 4, the temperature detection unit 99 needs a certain reaction time to measure the temperature, so under normal circumstances, the detection result measured by the temperature detection unit 99 will have a temperature measurement delay of 1-2s. During the rapid temperature rising and falling process, the temperature change of the carrier 4 can reach more than 30°C, so it is relatively difficult to control the carrier 4 through the temperature detection unit 99 during the rapid temperature rising and falling process. In this embodiment, the temperature of the carrier 4 is controlled by the dual temperature measurement method of resistance temperature measurement and calibration by the temperature detection unit 99.

[0151] In this embodiment, the temperature of the carrier 4 is controlled by the dual temperature measurement method of resistance temperature measurement and calibration by the temperature detection unit 99.

[0152] In order to more clearly describe how to calibrate the temperature detected by the resistance detection unit 99 in this embodiment, the temperature detection unit 99 is combined with the resistance detection unit 99 to calibrate the temperature detected by the resistance detection unit 99. Figure 19b As shown, a process of calibrating the resistance temperature measurement by the temperature detection unit 99 in an actual detection is shown. Before calibrating the temperature value, an initial RT temperature curve, i.e. a temperature preset curve, is preset, and then a very small current, such as a current less than 1mA, is applied to the heating element 451 of the carrier 4. The purpose of applying a very small current is to read the resistance of the heating element 451 without heating the heating element 451.

[0153] First calibration: the temperature detection unit 99 measures a first temperature calibration value T1, the resistance detection unit detects a first voltage U1 and a first current I1 of the heating element 451 at the temperature T1, and according to R=U / I, the resistance R1 of the heating element 451 at the temperature T1 can be obtained.

[0154] Second calibration: then the temperature detection unit 99 measures a second temperature calibration value T2, the resistance detection unit detects a second voltage U2 and a second current I2 of the heating element 451 at the temperature T2, and according to R=U / I, the resistance R2 of the heating element 451 at the temperature T2 can be obtained.

[0155] Finally, based on the two sets of linear equations in two variables: R1 = R0(1 + α) T1) and R2=R0(1+α) T2) T1 = T1 - T0, T2 = T2 - T0, R1 is the resistance value of heating element 451 at temperature T1, R2 is the resistance value of heating element 451 at temperature T2, α is the temperature coefficient of resistance of the material, T0 is the nominal temperature, and R0 is the nominal resistance value. By obtaining the specific values ​​of R0 and α, an accurate RT curve is obtained. Subsequently, the temperature of heating element 451 measured by the resistance temperature measurement method can be used as feedback for accurate temperature control.

[0156] 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.

[0157] like Figure 19a As shown, the heater 45 provided in this embodiment also includes a temperature calibration unit 93 for reflecting the temperature of the heating element 451. The temperature detection unit 99 detects the temperature of the heater 45 through the temperature calibration unit 93, which makes it easier for the temperature detection unit 99 to detect the temperature of the heater 45. It can be understood that when multiple heating elements 451 are controlled independently, each heating element 451 is provided with a temperature detection unit 99, a second contact 96, and a temperature calibration unit 93 to calibrate the heating element 451 respectively.

[0158] like Figure 19c As shown, when the temperature detection unit 99 is a contact temperature sensor, in order to facilitate temperature measurement by the temperature detection unit 99, the two first contacts of the temperature detection unit 99 are in contact with the two temperature calibration parts 93 respectively. The two temperature calibration parts 93 are not conductive. In this case, optionally, the heater 45 may also include an external electrical connection contact 97 and an electrical connection lead 98. The number of external electrical connection contact 97 and electrical connection lead 98 may both be two. The two external electrical connection contact 97 are located on the side of the two temperature calibration parts 93 that are far apart from each other. One external connection contact is electrically connected to one temperature calibration part 93 through an electrical connection lead 98, and the other external connection contact is electrically connected to the other temperature calibration part 93 through another electrical connection lead 98.

[0159] like Figure 19aAs shown, the temperature of the heat conduction layer 921 of the upper conduction assembly 92 is conducted to the temperature calibration part 93, which is electrically connected with an external resistance detection element at the external electrical connection contact 97 through the electrical connection lead 98. The external resistance detection element can detect the resistance of the temperature detection unit 99 through the external electrical connection contact 97, and then obtain the temperature of the temperature detection unit 99 according to the resistance. Optionally, the diameter of the electrical connection lead 98 is smaller than the temperature calibration part 93 and the external electrical connection contact 97, so that the heat loss of the temperature calibration part 93 through the electrical connection lead 98 is reduced, and the temperature calibration part 93 can better reflect the temperature of the upper conduction assembly 92, such as the temperature of the heat conduction layer 921 of the upper conduction assembly 92. The temperature detection unit 99 is in good electrical and thermal contact with the temperature calibration part 93 through the welding point. When the temperature of the upper conduction assembly 92, such as the temperature of the heat conduction layer 921 of the upper conduction assembly 92, changes, the temperature detection unit 99 can quickly and accurately perceive the temperature change. The temperature change causes the resistance of the temperature detection unit 99 to change, and the resistance change of the temperature detection unit 99 is detected in real time at the external electrical connection contact 97, so that real-time temperature detection is realized.

[0160] As shown in the figure, Figure 19a Optionally, in order to shorten the time for the temperature of the temperature calibration part 93 to be consistent with the temperature of the heating element 451, the carrier 4 can further include a rapid conduction part 94 for conducting the heat of the heating element 451 to the temperature calibration part 93. Specifically, in this embodiment, the heat of the heating element 451 is indirectly conducted to the temperature calibration part 93. For example, the heating element 451 heats the heat conduction layer 921, and the heat of the heat conduction layer 921 is conducted to the temperature calibration part 93 through the rapid conduction part 94. Thus, the temperature calibration part 93 accurately reflects the temperature of the heat conduction layer 921, and the temperature detection unit 99 can accurately measure the temperature of the heat conduction layer 921. Since the thickness of the reaction sample is very small, the temperature of the reaction sample is basically consistent with the temperature of the heat conduction layer 921. Therefore, the temperature of the reaction sample can be obtained by detecting the temperature of the temperature calibration part 93.

[0161] Preferably, one side of the rapid conduction part 94 is connected to the side of the upper conduction assembly 92 close to the heating element 451 or to the side of the lower conduction assembly 95 close to the heating element 451, and the other side is connected to the temperature calibration part 93. The lower surface of the upper conduction assembly 92 and the upper surface of the lower conduction assembly 95 are closest to the heating element 451, and their temperatures first approach the temperature of the heating element 451. Therefore, the rapid conduction part 94 is arranged in such a manner that the temperature of the rapid conduction part 94 is consistent with the temperature of the heating element 451 in the shortest time. Optionally, the rapid conduction part 94 is made of a material with high thermal conductivity, such as metal materials such as copper or aluminum, or thermally conductive ceramics, etc. The thermal conductivity of the rapid conduction part 94 is particularly superior to that of the lower conduction assembly 95, so as to quickly transfer heat to the temperature calibration part 93.

[0162] The rapid conducting part 94 includes a patch 941 and one or more conducting columns 942. The patch 941 is attached to the upper conducting assembly 92 on the side close to the heating element 451 or to the lower conducting assembly 95 on the side close to the heating element 451. One end of the conducting column 942 is connected to the patch 941, and the other end is connected to the temperature calibration part 93 through the lower conducting assembly 95. The lower surface of the upper conducting assembly 92 and the upper surface of the lower conducting assembly 95 are closest to the heating element 451, and their temperatures are closest to the temperature of the heating element 451. Therefore, the patch 941 can make the temperature of the rapid conducting part 94 consistent with the temperature of the heating element 451. The patch 941 can increase the contact area between the rapid conducting part 94 and the upper conducting assembly 92 or the lower conducting assembly 95, and improve the conducting efficiency. The cross-sectional area of the conducting column 942 can be smaller than the cross-sectional area of the patch 941. The temperature of the patch 941 can be rapidly conducted to the temperature calibration part 93, and the thermal resistance of the thermal resistance layer can be ensured to be as designed. Alternatively, the patch 941 and the conducting column 942 are made of high thermal conductivity materials such as copper. When the patch 941 and the conducting column 942 need to be made of insulating materials to avoid short circuit of the carrier 4, the patch 941 or the conducting column 942 can be made of high thermal conductivity ceramic materials.

[0163] It can be understood that the temperature calibration part 93 can be arranged one by one corresponding to the patch 941, and two temperature calibration parts 93 can also be connected to one patch 941. One temperature calibration part 93 can be connected to one conducting column 942. To improve the temperature uniformity of the temperature calibration part 93, the temperature calibration part 93 can be connected to multiple conducting columns 942.

[0164] As shown in Figure 19a To obtain the resistance of the heating element 451 and to supply power to the heating element 451, the second contact 96 is arranged on the outer surface of the carrier 4. The second contact 96 is arranged in multiple, and the second contact 96 is electrically connected to the heating element 451. The current and voltage of the heating element 451 can be obtained through the second contact 96, and the resistance value of the heating element 451 can be obtained.

[0165] In this embodiment, the second contact 96 enables the carrier 4 to realize the temperature measurement function of itself. Compared with the traditional structure which can only measure the temperature through an external temperature measurement unit, this embodiment can directly measure the temperature of the carrier 4 itself, so that the temperature measurement is more accurate and faster, and the accuracy and control speed of the temperature control system can be improved.

[0166] Embodiment Two

[0167] As shown in Figures 20a-22As shown, the carrier 4 of the second embodiment is basically the same as the carrier 4 of the first embodiment, and the difference between the two is that the carrier 4 of the second embodiment is not provided with the pressing cavity 46, and the outer side of the first wall 43 and / or the second wall 44 of the carrier 4 is provided with the external heater 200 to heat the reaction sample in the carrier 4.

[0168] As shown, the carrier 4 further comprises a liquid discharge part, and the liquid discharge part comprises a liquid discharge cavity 410, and the reaction sample in the sample containing cavity 41 can be transferred to the liquid discharge cavity 410. Optionally, a one-way valve (not shown in the figure), a two-way valve (not shown in the figure) or a film (not shown in the figure) is arranged between the liquid discharge cavity 410 and the sample containing cavity 41. Figure 20a As shown, the sample containing cavity 41 does not carry the reaction sample, and at this time, the carrier 4 is in an empty state; optionally, when the first wall 43 and the second wall 44 are connected with the side wall 42, the first wall 43 and / or the second wall 44 is not taut, so that, as shown,

[0169] Figure 20a As shown, when the sample containing cavity 41 is filled with the reaction sample, the first wall 43 and / or the second wall 44 protrudes outward, and the carrier 4 is in a full state. At this time, since the one-way valve, the two-way valve or the film stops the reaction sample in the sample containing cavity 41 from entering the liquid discharge cavity 410, the liquid discharge cavity 410 is not filled with the reaction sample. As shown, Figure 20b Figure 21 As shown, the first wall 43 and / or the second wall 44 is made of a deformable material, such as an aluminum film or an aluminum film and a pp film. When the external heater 200 presses the carrier 4, the first wall 43 and / or the second wall 44 deforms and approaches each other, and the surface of the first wall 43 and / or the second wall 44 changes from an arc shape to a plane, so that the external heater 200 is tightly attached to the first wall 43 and / or the second wall 44 of the carrier 4, and then the external heater 200 heats the entire first wall 43 and / or the second wall 43 corresponding to the sample containing cavity 41, the volume of the sample containing cavity 41 decreases, the pressure increases, the one-way valve or the two-way valve opens, or the film breaks, so that part of the reaction sample in the carrier 4 is transferred to the liquid discharge cavity 410, and at this time, the carrier 4 is in a pressure relief state. That is, the liquid discharge cavity 410 can accommodate the excess reaction sample in the sample containing cavity 41, so that the first wall 43 and / or the second wall 44 no longer protrudes outward, so that the external heater 200 heats the entire first wall 43 and / or the second wall 43 corresponding to the sample containing cavity 41, and then the amplification efficiency is improved. Since the carrier 4 is filled with the reaction sample, the reaction sample is also tightly attached to the first wall 43 and / or the second wall 43, so as to ensure the heat conduction efficiency between the external heater 200 and the reaction sample. At the same time, after the carrier 4 is converted from the full state to the pressure relief state, the thickness of the sample containing cavity 41 decreases, and the heat uniformity of the reaction sample in the sample containing cavity 41 can be further improved.

[0170] Although Figure 20b ​​In the embodiment shown in the drawings, only one of the first wall 43 and the second wall 44 is outwardly convex, and the other of the first wall 43 and the second wall 44 is rigid and cannot be deformed or has a smaller deformability than the outwardly convex first wall 43 or second wall 44. However, it should be understood by those skilled in the art that both the first wall 43 and the second wall 44 can be deformed to be outwardly convex, and two external heaters 200 are arranged on the two sides to heat the first wall 43 and the second wall 44, respectively. When the external heaters 200 heat the first wall 43 and the second wall 44, the two external heaters 200 press the carrier 4, so that the first wall 43 and the second wall 44 are deformed, the surfaces of the first wall 43 and the second wall 44 change from arc shapes to flat shapes, and the external heaters 200 are tightly attached to the first wall 43 and the second wall 44 of the carrier 4.

[0171] Optionally, the volume of the liquid discharge cavity 410 is determined, and when the carrier 4 is pressed, the liquid in the sample containing cavity 41 is transferred to the liquid discharge cavity 410 and fills the liquid discharge cavity 410, so as to facilitate the quantification of the reaction sample added into the carrier 4.

[0172] If the external heater 200 continuously contacts the carrier 4 during the amplification stage, the reaction sample in the liquid discharge cavity 410 can not be transferred into the carrier 4, and optionally, a one-way valve is arranged between the liquid discharge cavity 410 and the sample containing cavity 41. When the sample containing cavity 41 is pressed by the external heater 200, the pressure in the sample containing cavity 41 increases, the one-way valve opens, and the reaction sample enters the liquid discharge cavity 410.

[0173] As Figure 21 and Figure 22If the external heater 200 is intermittently separated from and contacted with the carrier 4 during the amplification stage, after the external heater 200 is separated from the carrier 4, the liquid discharge portion transfers the reaction sample into the carrier 4, at this time, a two-way valve can be arranged between the liquid discharge cavity 410 and the sample containing cavity 41, when the pressure in the sample containing cavity 41 increases due to being extruded, the two-way valve opens, the reaction sample enters into the liquid discharge cavity 410, when the external heater 200 is separated from the carrier 4, the two-way valve can be opened by extruding the liquid discharge portion, so that the reaction sample in the liquid discharge cavity 410 enters into the sample containing cavity 41. Or, in other optional embodiments, a film is arranged between the liquid discharge cavity 410 and the sample containing cavity 41, for example, the film can be a PDMS film, the thickness of the PDMS film can be several microns to tens of microns, for example, 15um, when the sample containing cavity 41 is extruded by the external heater 200, the film is broken, the reaction sample can enter into the liquid discharge cavity 410, when the external heater 200 is separated from the carrier 4, the reaction sample in the liquid discharge cavity 410 can enter into the sample containing cavity 41 by extruding the liquid discharge portion. It can be understood that the thickness of the film is smaller than the thickness of the first wall 43 and the second wall 44, so as to avoid the first wall 43 and the second wall 44 being extruded when the film is broken.

[0174] Although the present application has been described in detail with general description, specific embodiments and experiments, some modifications or improvements can be made on the basis of the present application, which is obvious to those skilled in the art. Therefore, these modifications or improvements made on the basis of not deviating from the spirit of the present application, are within the scope of the present application.

Claims

1. A carrier comprising a first wall (43) and a second wall (44) arranged opposite each other, and a side wall (42) arranged between the first wall (43) and the second wall (44), the first wall (43), the second wall (44) and the side wall (42) forming a sample receiving cavity (41), the sample receiving cavity (41) being of a flat structure, at least part of the side wall (42) being light transmissive, wherein, The first wall (43) and / or the second wall (44) is a heater (45) configured to heat a reaction sample in the sample containing cavity (41); The heater (45) comprises a heating element (451), the number of the heating element (451) is at least one, and the heating element is a resistance heating element; The heater (45) further comprises a temperature calibration part (93) configured to embody the temperature of the heating element (451); The heater (45) further comprises a rapid conduction part (94) configured to conduct the heat of the heating element (451) to the temperature calibration part (93); A temperature detection unit (99) is configured to detect the temperature of the temperature calibration part (93).

2. The carrier according to claim 1, wherein The number of the heating element (451) is at least two, and the at least two heating elements (451) are independent of each other.

3. The carrier according to any one of claims 1-2, wherein The carrier can further comprise a second contact (96) configured to allow a resistance detection element to detect the resistance of the heating element (451).

4. A kit comprising a reagent carrying part (3) and the carrier (4) according to any one of claims 1-3, wherein the reagent carrying part (3) is configured to carry at least one reagent.

5. The kit according to claim 4, wherein The reagent carrying part (3) and the carrier (4) are in one-piece structure; or The reagent carrying part (3) and the carrier (4) are in split structure; or The reagent carrying part (3) and the carrier (4) are detachably connected; or The reagent carrying part (3) and the carrier (4) are connected, and the included angle between the reagent carrying part (3) and the carrier (4) is adjustable.

6. The kit according to claim 4, wherein The reagent carrying part (3) comprises at least one pre-set reagent cavity (31).

7. The kit according to claim 6, wherein The reagent carrying part (3) further comprises at least one sample inlet cavity (32) and / or at least one empty cavity (33).

8. The kit according to claim 4, wherein The thickness direction of the sample containing cavity (41) or the carrier (4) is parallel or perpendicular to the depth direction of the cavity of the reagent carrying part (3).

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