WO2024250645A1 - Carrier and kit - Google Patents

Abstract

A carrier and a kit. The carrier comprises a first wall and a second wall arranged opposite to each other, 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 accommodating cavity; the sample accommodating cavity is of a flat structure; and at least part of the side wall is light-transmissive. The kit comprises a reagent carrying part and the carrier, and the reagent carrying part is at least configured to carry a reagent.

Description

A carrier and a kit

This application claims priority to Chinese patent application filed on June 5, 2023 and application number 2023106616694, the entire contents of which are incorporated by reference into this application.

Technical Field

The present application relates to the field of in vitro diagnostic technology, for example, to a vector and a kit.

Background Art

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 repeated thermal cycles of three steps: high temperature denaturation, low temperature annealing and suitable temperature extension. Before PCR amplification, the reaction sample needs to be placed in a carrier, where the reaction sample is formed by mixing samples such as collected throat swabs or nasal swabs and reagents used for PCR amplification. During PCR amplification, the reaction sample needs to be heated by a heater so that the reaction sample enters a high temperature denaturation and remains in the suitable temperature extension stage.

The carrier in the prior art is a tube structure such as an EP tube. The diameter of the area of the carrier containing the reaction sample is large, the heat-averaging speed is slow, and the temperature rise and fall speed of the reaction sample is slow. In addition, there is a groove on the bottom plate to form a receiving area for the reaction sample. The thickness of the bottom plate is relatively thick, and it is difficult to achieve rapid temperature rise and fall of the reaction sample.

The preparation of reaction samples is done by professional testers, which requires high professionalism; or it is prepared in PCR equipment, which requires the PCR equipment to be equipped with special containers to carry and equip the reagents required for PCR amplification, resulting in a complex structure of the PCR equipment. In addition, there is a gap between the carrier and the heater, and between the inner wall of the carrier and the reaction sample, resulting in low thermal conductivity and slow heating and cooling speed, which in turn leads to low PCR amplification efficiency.

Summary of the invention

One purpose of the present application is to propose a carrier to solve one of the above-mentioned technical problems.

To achieve the above-mentioned objectives, the first aspect of the present application provides a carrier, comprising a first wall and a second wall arranged opposite to each other, and a side wall arranged between the first wall and the second wall, wherein the first wall, the second wall and the side wall form a sample holding cavity, the sample holding cavity is a flat structure, and at least a portion of the side wall is light transmissive.

Optionally, the first wall and/or the second wall is a film made of a heat-conducting material.

Optionally, the first wall and/or the second wall is a heater, and the heater is configured to heat the reaction sample in the sample holding chamber.

Optionally, the carrier is a flat structure.

Optionally, the carrier further includes an extrusion cavity, and the extrusion cavity is deformed under an external force so as to cause the sample holding cavity to be deformed.

Optionally, the carrier includes an extrusion area and an amplification area, the extrusion cavity is arranged in the extrusion area, and the sample holding cavity is arranged in the amplification area.

Optionally, the first wall and the second wall corresponding to the extrusion area are formed of a deformable material.

Optionally, the extrusion chamber and the sample holding chamber are connected, or the extrusion chamber and the sample holding chamber are separated by an elastic membrane.

Optionally, the extrusion zone has an air inlet, the air inlet is provided with an air inlet portion, and the air inlet portion is configured to control the gas to enter the extrusion chamber.

Optionally, the first wall and the second wall are made of an aluminum film; or the first wall and the second wall are made of an aluminum film and an isolation film, and the isolation film is connected to a side of the aluminum film close to the sample holding cavity.

Optionally, the carrier further includes a first liquid inlet and a first exhaust hole communicated with the sample holding cavity.

Optionally, the first liquid inlet, the extrusion chamber, the sample holding chamber and the first exhaust hole are sequentially connected through a first channel.

Optionally, the extrusion chamber, the first liquid inlet and the first exhaust hole are all arranged on the same side of the sample holding chamber.

Optionally, the extrusion chamber and the first liquid inlet are located directly above the sample holding chamber, the first exhaust hole is located above the side of the sample holding chamber, one end of the first channel is connected to the lower end of the sample holding chamber, and the other end is connected to the first exhaust hole; or

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

Optionally, the first liquid inlet and the extrusion chamber are arranged on one side of the sample holding chamber, and the first exhaust hole is arranged on the other side of the sample holding chamber, and one side of the sample holding chamber is opposite to the other side of the sample holding chamber.

Optionally, the carrier further comprises a second liquid inlet and a second exhaust hole communicated with the sample holding cavity, and the second liquid inlet, the sample holding cavity and the second exhaust hole are communicated with each other in sequence through a second channel.

Optionally, the second liquid inlet and the second exhaust hole are located on the same side of the sample holding cavity, or on two opposite sides of the sample holding cavity.

Optionally, the liquid inlet and/or the vent are sealed with a sealing cover, a thermoplastic seal, a pressure-sensitive adhesive or a plug. The vent hole is sealed, or a breathable and water-tight membrane is provided on the vent hole.

Optionally, the carrier further comprises a drainage portion, wherein the drainage portion comprises a drainage cavity, and the reaction sample in the sample holding cavity can be transferred to the drainage cavity.

Optionally, a one-way valve, a two-way valve or a film is provided between the drainage cavity and the sample holding cavity.

Optionally, the first wall and the second wall are made of deformable material.

Optionally, the heater includes a heating element, and the number of the heating element is at least one.

Optionally, the number of the heating elements is at least two, and at least two of the heating elements are independent of each other.

Optionally, the carrier further includes a temperature detection unit configured to detect the temperature of the carrier.

Optionally, the heater further comprises a temperature calibration portion configured to reflect the temperature of the heating element, and the temperature detection unit is configured to detect the temperature of the temperature calibration portion.

Optionally, the heater further comprises a rapid conduction portion, wherein the rapid conduction portion is configured to conduct the heat of the heating element to the temperature calibration portion.

Optionally, the carrier may further include a second contact point, wherein the second contact point is configured for the resistance detection element to detect the resistance of the heating element.

Optionally, the flat structure means that the dimension of the sample holding cavity or the carrier in a direction perpendicular to its thickness direction is larger than its dimension in the thickness direction.

Optionally, the ratio of the dimension of the sample holding cavity or the carrier in a direction perpendicular to its thickness direction to its thickness direction is greater than 5:1.

Optionally, the ratio of the dimensions is 50:1 to 100:1.

Another object of the present application is to provide a kit to solve one of the above-mentioned technical problems.

To achieve this object, the second aspect of the present application adopts the following technical solution: a reagent kit, comprising a reagent carrying portion and the carrier, wherein the reagent carrying portion is at least configured to carry the reagent.

Optionally, the reagent carrying portion and the carrier are an integrated structure; or

The reagent carrying portion and the carrier are of separate structures; or

The reagent carrying portion is detachably connected to the carrier; or

The reagent carrying portion is connected to the carrier, and the angle between the reagent carrying portion and the carrier is adjustable.

Optionally, the reagent carrying portion includes at least one pre-set reagent cavity.

Optionally, the agent carrying portion further includes at least one injection cavity and/or at least one cavity.

Optionally, the thickness direction of the sample holding cavity or the carrier is parallel or perpendicular to the depth direction of the cavity of the agent carrying portion.

As can be seen from the above, the technical solution provided by the present application, the sample holding cavity is a flat structure, which will make the thickness of the reaction sample in the sample holding 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 consistency in a very short time, and the heat transfer efficiency is high, so that the reaction sample temperature rise and fall speed and detection efficiency are greatly improved. However, the inner diameter of the PCR tube is relatively large compared to the flat structure of the holding cavity, and the distance between the center of the reaction sample and the surface of the liquid is very large. It takes a long time for the temperature of the reaction sample to reach consistency, and the reaction sample temperature rise and fall speed is low, and the detection efficiency is low.

The test kit includes a reagent carrying part and the above-mentioned carrier, and the reagent carrying part is at least configured to carry the reagent. Therefore, after collecting the sample, the reagent in the reagent carrying part can be directly used to configure the reaction sample, thereby improving the detection efficiency. At the same time, the reagent in the reagent carrying part can be quantitatively placed according to the actual amount required, and can be operated without professional testers, which has universal applicability. In addition, the PCR equipment does not need to be specially provided with a container for carrying the reagent and configuring the reagent, thereby simplifying the structure of the PCR equipment.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1a is a schematic structural diagram of a first carrier provided in an embodiment of the present application;

Fig. 1b is a cross-sectional view of the carrier at C-C in Fig. 1a;

Fig. 2 is a cross-sectional view of the carrier at D-D in Fig. 1b;

FIG3 is an exploded view of a second carrier, an external heater and a cooling mechanism provided in an embodiment of the present application;

4 is a schematic diagram of the internal structure of a second carrier, an external heater and a cooling mechanism provided in an embodiment of the present application;

FIG5 is an exploded view of a third carrier and cooling mechanism provided in an embodiment of the present application;

FIG6 is a schematic diagram of the internal structure of the carrier provided in FIG5 ;

FIG7 is a schematic diagram of the structure of a fourth carrier provided in an embodiment of the present application;

FIG8a is a schematic structural diagram of the fourth carrier provided in an embodiment of the present application from another perspective;

FIG8b is a schematic diagram of the structure of one of the carriers provided in an embodiment of the present application;

FIG9a is a schematic diagram of the structure of the fifth carrier provided in an embodiment of the present application;

FIG9b is a schematic structural diagram of the extrusion cavity of the carrier provided in FIG9a when the extrusion cavity extrudes the sample receiving cavity;

FIG10 is a schematic diagram of the structure of the sixth carrier provided in an embodiment of the present application;

FIG11a is a schematic diagram of the structure of a seventh carrier provided in an embodiment of the present application;

FIG11b is a schematic structural diagram of an eighth carrier provided in an embodiment of the present application;

FIG12 is a schematic diagram of the structure of a ninth carrier provided in an embodiment of the present application;

FIG13 is a schematic diagram of the structure of the tenth carrier provided in an embodiment of the present application;

FIG14 is a schematic diagram of the structure of the first kit provided in an embodiment of the present application;

FIG15 is a schematic diagram of a reaction sample configuration process provided in an embodiment of the present application;

16 is a schematic diagram of the structure of the first kit provided in an embodiment of the present application when an external heater or cooling mechanism is inserted;

17 is a schematic structural diagram of the first reagent kit provided in an embodiment of the present application when it is bent and inserted into an external heater or cooling mechanism;

18 is a schematic structural diagram of the second kit provided in an embodiment of the present application when an external heater or cooling mechanism is inserted;

FIG19a is a schematic diagram of the internal structure of a carrier including two heaters provided in an embodiment of the present application;

FIG19b is a graph of temperature calibration provided in an embodiment of the present application;

FIG19c is a schematic structural diagram of the outer surface of a carrier provided in an embodiment of the present application;

FIG20a is a schematic structural diagram of the eleventh carrier provided in an embodiment of the present application in an unloaded state;

FIG20b is a schematic structural diagram of the carrier in FIG20a in a fully loaded state;

FIG21 is a schematic diagram of an external heater pressing down the carrier in FIG20b, and the carrier is in a depressurized state;

FIG. 22 is a schematic diagram of the external heater when it is away from the carrier in FIG. 21 .

In the figure:
3. Reagent carrying part; 31. Pre-reagent chamber; 32. Sample injection chamber; 33. Cavity; 34. Sealing film;
4. carrier; 41. sample holding chamber; 411. first side; 412. second side; 42. side wall; 43.
first wall; 44, second wall; 45, heater; 451, heating element; 46, extrusion chamber; 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, drainage chamber;
92. Upper conduction component; 921. Heat-saturating layer; 93. Temperature calibration unit; 94. Rapid conduction unit; 941.
SMD; 942, guide pillar; 95, lower conductive component; 951, insulating thermal resistance layer; 952, thermal conductive layer; 96, second contact point; 97, external electrical connection contact point; 98, electrical connection lead;
99. Temperature detection unit;
100. Test kit;
200, external heater; 201, cooling mechanism; 203, detection unit; 204, pipette gun; 205,
Blowing pieces.

DETAILED DESCRIPTION

Some directional words are defined in the present application. Unless otherwise stated, the directional words used, such as "up", "down", "left", "right", "inside" and "outside", are used for ease of understanding and therefore do not constitute a limitation on the scope of protection of the present application.

In the present application, unless otherwise clearly specified and limited, a first feature being "above" or "below" a second feature may include that the first and second features are in direct contact, or may include that the first and second features are not in direct contact but are in contact through another feature between them. Moreover, a first feature being "above", "above" and "above" a second feature includes that the first feature is directly above and obliquely above the second feature, or simply indicates that the first feature is higher in level than the second feature. A first feature being "below", "below" and "below" a second feature includes that the first feature is directly below and obliquely below the second feature, or simply indicates that the first feature is lower in level than the second feature.

In the description of this application, unless otherwise clearly specified and limited, the terms "connected", "connected", and "fixed" should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection or an indirect connection through an intermediate medium, it can be the internal connection of two elements or the interaction relationship between two elements. For ordinary technicians in this field, the specific meanings of the above terms in this application can be understood according to specific circumstances.

Embodiment 1

This embodiment provides a carrier 4 for use in PCR sampling, amplification and/or detection, but is not limited thereto. The carrier 4 may be a consumable, that is, disposable.

As shown in Fig. 1a-Fig. 2, the carrier 4 provided in this embodiment includes a first wall 43 and a second wall 44 arranged opposite to 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 form a sample holding chamber 41. The sample holding chamber 41 is a flat structure, and at least part of the side wall 42 is light-transmissive. In particular, fluorescence can pass through the side wall 42 of the sample holding chamber 41. As an example, the side wall 42 can be made of dimethylsiloxane (i.e., PDMS), polypropylene (i.e., PP), organic glass (i.e., PMMA) or polycarbonate (i.e., PC). PMMA, PDMS, PP and PC are optically transparent materials with good biocompatibility, so they can meet the requirements of fluorescence detection and have no effect on the reaction sample. As an example, the sample holding chamber 41 is an amplification chamber used in a PCR reaction.

Optionally, the side walls 42 are all light-transmissive and can be an integrated structure for ease of processing. It is understood that the side walls 42 are annular structures, which refer to structures that are continuously extended and closed. The annular structures are not limited to circular rings, but can also be polygonal rings such as rectangles, elliptical rings, or irregular rings, etc. As long as the side wall 42 can enclose a space, it is sufficient. Optionally, the side wall 42 is formed by injection molding, such as directly forming a ring-shaped side wall 42, or a through hole is formed on a light-transmitting plate by laser or other means, and then the first wall 43 and the second wall 44 are connected to opposite sides of the side wall 42 by a film bonding process such as gluing or welding, thereby forming the sample holding chamber 41.

The sample holding cavity 41 is a flat structure, which makes the thickness of the reaction sample in the sample holding cavity 41 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 43 and the second wall 44 is heated, the temperature of the reaction sample can reach a uniform temperature in a very short time, and the heat transfer efficiency is high, so that the reaction sample temperature rise and fall speed and detection efficiency are greatly improved. However, the inner diameter of the PCR tube is relatively large compared to the flat structure of the holding cavity, and the distance between the center of the reaction sample and the surface of the liquid is very large. It takes a long time for the temperature of the reaction sample to reach a uniform temperature, and the reaction sample temperature rise and fall speed is low, and the detection efficiency is low.

As shown in Figures 3 to 6, at least part of the side wall 42 of the sample holding chamber 41 is light-transmissive, and the detection unit 203 for detecting the fluorescent signal excited by the reaction sample in the sample holding chamber 41 can be detected through the light-transmissive side wall 42, especially when the first wall 43 and the second wall 44 are both not light-transmissive, such as when the first wall 43 and the second wall 44 are both heaters 45 for heating the reaction sample or the first wall 43 and the second wall 44 are heated by an external heater 200.

In an optional embodiment, the carrier 4 is a flat structure, and the structure of the carrier 4 is consistent with the structure of the sample holding cavity 41, so that the first wall 43 and the second wall 44 can be very thin. Compared with the method of making grooves on the bottom plate to form a holding area for accommodating the reaction sample, since there is no need to heat a very thick bottom plate, the carrier 4 and the reaction sample therein can be heated and cooled faster.

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

Optionally, the first wall 43 and/or the second wall 44 is a film 409 made of a heat-conducting material, and in particular, the side of the carrier 4 heated by the external heater 200 is a film 409 made of a heat-conducting material. Specifically, the film 409 is an aluminum film and Isolation membrane, optionally, the isolation membrane is a polypropylene film (i.e., PP film). The isolation membrane is in direct contact with the reaction liquid to prevent the influence of the aluminum film on the reaction sample. The thickness of the aluminum film can be tens of μm, such as 30 μm, 60 μm, etc., and the aluminum film of this thickness can be deformed and has a certain strength. The thickness of the isolation membrane can be 10-30 μm, such as 20 microns, etc., as long as the isolation membrane can separate the reaction sample from the aluminum film. Of course, the film 409 can also be an aluminum film without the need for a PP film. The thickness of the aluminum film can be tens of μm, such as 30 μm, 60 μm, etc., and the aluminum film of this thickness can be deformed and has a certain strength. In particular, the side of the carrier 4 heated by the external heater 200 is a film 409 made of a heat-conducting material.

As shown in FIG. 3 and FIG. 4 , in an optional embodiment, the first wall 43 and the second wall 44 of the carrier 4 are both films 409 made of heat-conducting materials. 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 of the external heater 200 to the reaction sample in the sample holding chamber 41. At this time, rapid heating and cooling are achieved by 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, the device structure is more compact and the detection efficiency is further improved relative to the method of performing fluorescence detection through the first wall 43 or the second wall 44. At the same time, the first wall 43 and the second wall 44 of the carrier 4 with a flat structure can make the contact area between the carrier 4 and the external heater 200 large, thereby further accelerating the heating and cooling speed.

As shown in Figures 5 and 6, the carrier 4 includes at least one heater 45, and the first wall 43 and/or the second wall 44 are heaters 45, and the heater 45 is configured to heat the reaction sample in the sample holding chamber 41. In this case, it is not necessary to heat the reaction sample through the external heater 200. That is, as shown in Figure 5, the first wall 43 and the second wall 44 are heaters 45, and the heater 45 is in direct contact with the reaction sample in the carrier 4. When the first wall 43 and the second wall 44 are heaters 45, the heating speed of the reaction sample is further improved, and at the same time, the detection unit 203 performs detection from the side, especially, from both sides or more sides.

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 there is no air layer between the heater 45 and the sample holding cavity 41, thereby accelerating the heat transfer speed between the heater 45 and the reaction sample in the sample holding cavity 41, thereby 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 contact area between the flat structure carrier 4 and the heater 45 is large, and the temperature rise and fall speed of the reaction sample is faster.

As shown in FIG. 7 and FIG. 8a , in an optional embodiment, especially when the carrier 4 does not include the heater 45, the carrier 4 further includes an extrusion chamber 46, and the extrusion chamber 46 is deformed under the external force F to deform the sample receiving chamber 41, so that the extrusion chamber 46 controls the pressure in the sample receiving chamber 41. Specifically, the extrusion chamber 46 is connected to the sample receiving chamber 41 through the first channel 403.

For example, during PCR amplification, the extrusion chamber 46 is squeezed to squeeze the gas and/or liquid (the liquid may be The reaction sample in the sample receiving chamber 41 is pressed by the reaction sample, and the reaction sample squeezes the first wall 43 and the second wall 44 corresponding to the sample receiving chamber 41, so that the first wall 43 and the second wall 44 corresponding to the sample receiving chamber 41 expand outwards. When the external heater 200 is provided on the outer side of the first wall 43 and the second wall 44 corresponding to the sample receiving chamber 41, the first wall 43 and the second wall 44 corresponding to the sample receiving chamber 41 are attached to the external heater 200. At the same time, the reaction sample is attached to the inner side of the first wall 43 and the second wall 44 corresponding to the sample receiving chamber 41 under the pressure of the squeezing chamber 46, and because the outer side of the first wall 43 and the second wall 44 corresponding to the sample receiving chamber 41 is attached to the external heater 200, the heat conduction efficiency can be greatly improved. In this embodiment, the extrusion chamber 46 is filled with gas such as air. The thermal conductivity of gas is lower than that of liquid, and gas has a heat-insulating 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 extrusion chamber 46 is small, which is conducive to uniform temperature of the reaction sample and rapid temperature rise and fall. At the same time, when the extrusion chamber 46 is filled with gas such as air, 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 due to the need to heat and fall the excess liquid.

Continuing with FIG. 7 and FIG. 8a , the carrier 4 includes an extrusion area 47 and an amplification area 48, the extrusion cavity 46 is disposed in the extrusion area 47, and the sample holding cavity 41 is disposed in the amplification area 48. The extrusion cavity 46 can be deformed by extruding the extrusion area 47, the amplification area 48 can be deformed, and the cavity wall of the amplification area 48 can be deformed and fit on the external heater 200. As shown in FIG. 8a , the extrusion cavity 46 can be extruded by simultaneously extruding the first wall 43 and the second wall 44. Of course, as shown in FIG. 8b , 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 of the first wall 43 and the second wall 44 on a plane.

As shown in FIG. 7 , further optionally, the first wall 43 and the second wall 44 corresponding to the amplification zone 48 are a membrane 409 made of a heat-conductive material (for example, the elliptical area surrounded by the dotted line in FIG. 7 , but not limited thereto), and an external heater 200 is correspondingly arranged on the outer side of the first wall 43 and the second wall 44 corresponding to the amplification zone 48, and no external heater 200 is arranged at the extrusion zone 47, that is, the outer side of the extrusion zone 47 is left vacant to facilitate extrusion of the extrusion zone 47.

The first wall 43 and the second wall 44 corresponding to the extrusion area 47 are formed of a deformable material, so that when the extrusion area 47 is extruded, the extrusion area 47 and the extrusion cavity 46 are deformed. As shown in FIG7 and FIG8a, optionally, the deformable material is an aluminum film or an aluminum film and a PP film, and the first wall 43 and the second wall 44 of the carrier 4 are both integral structures, and the first wall 43 and the second wall 44 are also the outer walls of the amplification area 48 and the extrusion cavity 46.

As shown in Figures 7 and 8a, in this embodiment, the extrusion chamber 46 is connected to the sample holding chamber 41. Optionally, the extrusion chamber 46 and the sample holding chamber 41 are connected through a first channel 403. The extrusion chamber 46 has gas, or gas and reaction sample, or only reaction sample. The extrusion chamber 46 is squeezed, and the gas and/or reaction sample squeeze the reaction sample in the sample holding chamber 41.

As shown in Fig. 7, Fig. 8a, Fig. 8b and Fig. 10, the carrier 4 may further include a first liquid inlet 401 and a first vent 402 that are in communication with the sample holding chamber 41. The reaction sample enters the sample holding chamber 41 through the first liquid inlet 401, and the gas in the sample holding chamber 41 is discharged through the first vent 402. The first liquid inlet 401, the extrusion chamber 46, the sample holding chamber 41 and the first vent 402 are sequentially connected through the first channel 403. Optionally, the first liquid inlet 401 and the first vent 402 may be provided on the first wall 43 or the second wall 44 as shown in Fig. 8a. Of course, as shown in Fig. 8b, the first liquid inlet 401 and the first vent 402 may also penetrate the side wall 42 of the carrier 4, that is, the first liquid inlet 401 and the first vent 402 are located on the side wall 42.

The reaction sample first enters the extrusion chamber 46 from the first liquid inlet 401, and then enters the amplification zone 48 from the extrusion chamber 46. In addition, before sealing the first exhaust hole 402, the extrusion chamber 46 can be slightly squeezed to ensure that the gas in the sample holding chamber 41 is squeezed to the first exhaust hole 402, thereby ensuring that the sample holding chamber 41 is filled with the reaction sample, thereby ensuring that there are no or very few bubbles in the amplification zone 48. It can be understood that since the thickness of the sample holding chamber 41 in this embodiment is very thin, when the fluorescence detection device performs fluorescence detection through the side wall 42 of the sample holding chamber 41, if there are bubbles in the sample holding chamber 41, it is easy to affect the result of the fluorescence detection. Among them, the bubbles only need to avoid the light part of the fluorescence detection device. When the carrier 4 is placed vertically (i.e., the direction shown by the arrow L in Figure 10 is upward), the bubbles can accumulate at the position where the light part of the upper end of the carrier 4 does not pass. In addition, one of the reasons for setting the sample holding chamber 41 to a flat structure is to achieve rapid temperature rise and fall of the reaction sample. If there are bubbles, especially a bubble layer, in the sample holding chamber 41, the heat conduction efficiency in the bubbles is greatly reduced, which will affect the temperature rise and fall speed and the temperature uniformity of the reaction sample. Therefore, in this embodiment, the first exhaust hole 402 can discharge the bubbles in the amplification zone 48. The absence of bubbles or the presence of very few bubbles in the amplification zone 48 can ensure the accuracy of the fluorescence detection results, as well as the temperature uniformity of the reaction sample and the amplification efficiency. Another reason for setting the sample holding chamber 41 to a flat structure is that when the carrier 4 is placed vertically (i.e., the direction shown by the arrow L in Figure 10 is upward), the liquid thermal convection is conducive to further mixing the liquid and removing bubbles.

As shown in Fig. 7 and Fig. 10, the first liquid inlet 401 and the extrusion cavity 46 are arranged on one side of the sample holding cavity 41, and the first exhaust hole 402 is arranged on the other side of the sample holding cavity 41, and one side of the sample holding cavity 41 is opposite to the other side of the sample holding cavity 41. When the reaction sample is added into the sample holding cavity 41 through the first liquid inlet 401, the reaction sample first passes through the extrusion cavity 46 and then flows into the sample holding cavity 41, and the gas in the sample holding cavity 41 can be exhausted through the first exhaust hole 402.

As shown in FIG9a, of course, in other optional embodiments, the outer wall of the extrusion cavity 46 may not be the first wall 43 and the second wall 44, but the extrusion area 47 includes an elastic membrane 49, and the elastic membrane 49 surrounds the extrusion cavity 46. In this embodiment, the elastic membrane 49 is a membrane that can restore its original shape after deformation. The material forming the elastic film 49 may 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 is elastic and can restore the original shape, such as 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 realize repeated extrusion of the extrusion cavity 46, and can cause the reaction sample in the sample holding cavity 41 to flocculate, thereby mixing the reaction sample, thereby improving the temperature uniformity of the reaction sample. In addition, when the first wall 43 and the second wall 44 are aluminum film or aluminum film and PP film, and the cavity wall corresponding to the extrusion cavity 46 is an elastic film 49, it is not easy to restore the deformation after the aluminum film bulges outward. If the extrusion cavity 46 is squeezed repeatedly, the aluminum film corresponding to the sample holding cavity 41 will bulge during the first squeezing. After the extrusion cavity 46 is released, the aluminum film corresponding to the sample holding cavity 41 will not restore its shape. Therefore, after the extrusion cavity 46 is released, there will be a tiny gap between the reaction sample and the aluminum film. Therefore, during the amplification process, the extrusion cavity 46 is repeatedly squeezed, so that the liquid in the sample holding cavity 41 forms floccules, and the liquid is mixed evenly, thereby improving the amplification efficiency.

As shown in FIG9a, in other embodiments, the extrusion chamber 46 and the sample holding chamber 41 are not connected, but the extrusion chamber 46 and the sample holding chamber 41 are separated by an elastic membrane 49, thereby preventing the gas or/and solution in the extrusion chamber 46 from contaminating the sample holding chamber 41. In addition, the gas in the extrusion chamber 46 can be prevented from entering the sample holding chamber 41, thereby preventing bubbles from forming in the sample holding chamber 41, affecting the heat conduction between the heater and the reaction sample and affecting the detection of the reaction sample. At the same time, repeated extrusion of the extrusion chamber 46 can cause turbulence in the sample in the sample holding chamber 41, thereby mixing the reaction sample and improving the temperature uniformity of the reaction sample.

At this time, the first liquid inlet 401 , the sample holding chamber 41 and the first exhaust hole 402 are connected in sequence through the first channel 403 .

As shown in FIG. 9b, the extrusion chamber 46 contains gas and/or solution, and the extrusion chamber 46 is extruded, and the elastic membrane 49 adjacent to the amplification zone 48 expands toward the side where the amplification zone 48 is located, and then the elastic membrane 49 squeezes the reaction sample in the sample holding chamber 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 extrusion chamber 46 stores gas such as air, and the thermal conductivity of the gas is low relative to that of the liquid. The gas has a heat-insulating effect. During the nucleic acid amplification stage, the reaction sample is repeatedly heated and cooled. At this time, the reaction sample and the gas in the extrusion chamber 46 have less heat exchange, which is conducive to uniform temperature of the reaction sample and rapid temperature rise and fall. At the same time, when the extrusion chamber 46 stores gas such as air, 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 due to the need to heat and fall the excess liquid.

In yet another optional embodiment, in order to enable the extrusion chamber 46 to control the pressure of the sample holding chamber 41, the extrusion chamber 46 is connected to the sample holding chamber 41, and the extrusion area 47 has an air inlet, and the air inlet is provided with an air inlet portion ( FIG. (not shown in the figure), the air inlet is configured to control the gas entering the extrusion chamber 46. If the air inlet is a breathable and water-tight membrane covering the air inlet, the breathable and water-tight membrane can allow gas to pass through, but does not allow liquid to pass through. During PCR amplification, gas is introduced into the extrusion chamber 46 through the breathable and water-tight membrane to control the pressure of the extrusion chamber 46, so that the extrusion chamber 46 applies pressure to the reaction sample in the sample holding chamber 41. The air inlet is a one-way valve. When air is ventilated to the air inlet through an inflation device such as a pump, the one-way valve is opened under pressure, and gas enters the extrusion chamber 46 to control the pressure of the extrusion chamber 46, so that the extrusion chamber 46 applies pressure to the reaction sample in the sample holding chamber 41.

More embodiments of the liquid inlet, the exhaust hole and the channel are described below. As shown in Fig. 11a and Fig. 11b, the extrusion chamber 46, the first liquid inlet 401 and the first exhaust hole 402 are all arranged on the same side of the sample holding chamber 41. When the reaction sample is added to the sample holding chamber 41, the gas in the amplification zone 48 can be discharged from the first exhaust hole 402. At the same time, when performing PCR amplification and/or detection, the carrier 4 is placed vertically, and the direction indicated by the arrow L in Fig. 11a is upward. When the reaction sample is added to the sample holding chamber 41, the gas in the amplification zone 48 can be squeezed to the first exhaust hole 402 for discharge.

Optionally, as shown in FIG11a, the extrusion chamber 46 and the first liquid inlet 401 are located directly above the sample holding chamber 41, the first exhaust hole 402 is located above the side of the sample holding chamber 41, and one end of a first channel 403 is connected to the lower end of the sample holding chamber 41, and the other end is connected to the first exhaust hole 402. When the reaction sample is added to the sample holding chamber 41, the gas in the amplification region 48 can be discharged from the first exhaust hole 402 or discharged to the extrusion chamber 46.

More preferably, as shown in FIG11b, the first vent hole 402 is located directly above the sample holding chamber 41, the extrusion chamber 46 and the first liquid inlet 401 are located above the side of the sample holding chamber 41, and one end of a first channel 403 is connected to the lower end of the sample holding chamber 41, and the other end is connected to the extrusion chamber 46. It can be understood that the sample holding chamber 41 has a first side 411 and a second side 412 opposite to each other. When the carrier 4 is used, the first side 411 is located above the second side 412, the first vent hole 402 is located directly above the first side 411, and the extrusion chamber 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 holding chamber 41, and the other end is connected to the extrusion chamber 46, and one end of another first channel 403 is connected to the first vent hole 402, and the other end is connected to the first side 411 of the sample holding chamber 41. On the one hand, when liquid is injected into the sample holding chamber 41, the air floats up and is more easily discharged from the first exhaust hole 402; on the other hand, during the amplification stage, even if the extrusion chamber 46 is not full of reaction samples, when the extrusion chamber 46 is extruded, the reaction samples in the first channel 403 will enter the sample holding chamber 41, thereby preventing the air in the extrusion chamber 46 from entering the sample holding chamber 41, thereby ensuring that the reaction samples in the sample holding chamber 41 are not contaminated; on the other hand, the gas precipitated from the reaction sample in the sample holding chamber 41 during the heating process in the amplification stage is more likely to float up to the first exhaust hole 402, and when the end face of the first exhaust hole 402 is covered with an air-permeable and water-impermeable membrane, the gas can also be discharged.

The first exhaust hole 402 is located at the top to facilitate bubbles in the sample holding cavity 41 to float to the first exhaust hole 402 , thereby preventing bubbles from appearing on the sides of the amplification region 48 close to the first wall 43 and the second wall 44 , thereby ensuring the accuracy of detection by the detection unit 203 .

As shown in Figures 12 and 13, when the carrier 4 does not include the extrusion chamber 46, the carrier 4 also includes a second liquid inlet 404 and a second exhaust hole 405 that are connected to the sample holding chamber 41. The reaction sample enters the sample holding chamber 41 through the second liquid inlet 404, and the gas in the sample holding chamber 41 is discharged through the second exhaust hole 405. Specifically, the second liquid inlet 404, the sample holding chamber 41 and the second exhaust hole 405 are connected in sequence through the second channel 406. At this time, the first wall 43 and the second wall 44 of the carrier 4 can both be heaters 45 for heating the reaction sample, or can both be films 409 made of heat-conducting materials.

As shown in FIG12, the second liquid inlet 404 and the second exhaust hole 405 are located on opposite sides of the sample holding chamber 41. When the reaction sample is added to the sample holding chamber 41, the gas in the amplification region 48 can be exhausted through the second exhaust hole 405. Optionally, the second liquid inlet 404 and the second exhaust hole 405 can be provided on the first wall 43 or the second wall 44 as shown in FIG12. Of course, as shown in FIG11b, the second liquid inlet 404 and the second exhaust hole 405 can also penetrate the side wall 42 of the carrier 4, that is, the second liquid inlet 404 and the second exhaust hole 405 are located on the side wall 42.

As shown in FIG13 , the second liquid inlet 404 and the second exhaust hole 405 are located on the same side of the sample holding chamber 41. When the reaction sample is added into the sample holding chamber 41, the gas in the amplification zone 48 can be discharged from the second exhaust hole 405. At the same time, when performing PCR amplification and/or detection, the carrier 4 is placed vertically, that is, the direction shown by the arrow L in FIG13 is upward, and the second exhaust hole 405 is located at the top, so that the bubbles in the sample holding chamber 41 can float to the second exhaust hole 405, thereby avoiding the appearance of bubbles in the amplification zone 48 near the sides of the first wall 43 and the second wall 44, thereby ensuring the accuracy of the detection by the detection unit 203.

As shown in Figure 7, the liquid inlet and/or the vent can be sealed by a sealing cover 407, and the sealing cover 407 can be an integral structure with the carrier 4. Of course, the liquid inlet and/or the vent can also be sealed by a thermoplastic seal, a pressure-sensitive adhesive or a plug. Before amplification, the liquid inlet and the vent are sealed by a sealing cover 407, etc., so as to avoid evaporation of the reaction sample and contamination, and at the same time, it is convenient to maintain a certain pressure in the sample holding chamber 41. Of course, a breathable and water-impermeable membrane can also be set on the vent, so that the reaction sample is not discharged through the vent, and at the same time, the gas in the sample holding chamber 41 can be discharged.

As shown in FIG14 , this embodiment also provides a reagent kit 100, including a reagent carrying portion 3 and the above-mentioned carrier 4. The reagent carrying portion 3 is at least configured to carry reagents. Therefore, after collecting the sample, the reagents in the reagent carrying portion 3 can be directly used to configure the reaction sample, thereby improving the detection efficiency. At the same time, the reagents in the reagent carrying portion 3 can be quantitatively placed according to the actual amount required, and can be operated without the need for professional test personnel, which is universal. In addition, there is no need for the PCR equipment to be specially equipped with containers for carrying reagents and configuring reagents. And simplify the structure of PCR equipment.

As shown in FIG14 , the reagent carrying portion 3 may include at least one preset reagent chamber 31, in which the reagent is placed. The reagent carrying portion 3 may also include at least one injection chamber 32 and/or at least one cavity 33. The injection chamber 32 may be used to place a pharyngeal swab or a liquid sample, and the cavity 33 may be configured as a mixed reagent. The injection chamber 32, the preset reagent chamber 31, and the cavity 33 may be provided with a total of 5, and of course, more than 5 or less than 5 as needed.

At least one injection cavity 32, at least one preset reagent cavity 31, and at least one cavity 33 are provided with openings, and the openings are configured to allow reagents or samples to enter and exit the cavity. A sealing film 34 is provided on the openings. Before using the reagent kit 100, the sealing film 34 is opened, and before that, the cavity is isolated from the outside world, so that the cleanliness of the cavity can be ensured.

The injection chamber 32, the preset reagent chamber 31 and the cavity 33 are covered with a sealing film 34. When sampling, the entire sealing film 34 can be torn off by manual or automated equipment. Or, the sealing film 34 can also be a split structure, such as: a sealing film 34 can be set at the open end of the injection chamber 32. Before placing the throat swab or liquid sample, the user can remove the sealing film 34 by manual or automated equipment, and then put the sample into the injection chamber 32. The sealing film 34 can ensure that the injection chamber 32 is not contaminated. The preset reagent chamber 31 and the cavity 33 can be covered with another sealing film 34. When the reagent needs to be configured, the sealing film 34 is removed by manual or automated equipment, and the pipette gun 204 absorbs the reagent in the preset reagent chamber 31, and moves the reagent into the cavity 33 to configure the reagent, and transfers the reaction sample formed by the reagent and the sample to the carrier 4.

FIG. 15 schematically shows the process of preparing a reaction sample using a reagent kit 100 by manual or automated equipment. For example, the injection chamber 32 is configured to accommodate a sample processing liquid, and two preset reagent chambers 31 are provided, which are respectively configured to accommodate a PCR reaction buffer and an enzyme system:

Step 1, tear off the sealing film 34;

Step 2, placing the collected sample into the injection chamber 32;

Step 3, transferring the PCR reaction buffer in one of the preset reagent chambers 31 to the cavity 33;

Step 4, transferring the enzyme system in another preset reagent chamber 31 to the cavity 33;

Step 5, transferring the sample processing liquid in the injection chamber 32 to the cavity 33;

Step 6, mixing the reaction sample in the cavity 33 by blowing the member 205;

Step 7, transferring the reaction sample in the cavity 33 to the carrier 4 by using the pipette gun 204;

Step 8, sealing the liquid inlet and the exhaust hole, and again placing a sealing film 34 on the opening.

As shown in FIGS. 14 and 16 , the thickness direction of the sample holding cavity 41 or the carrier 4 (the direction indicated by arrow H in FIG. 14 ) is parallel to the depth direction of the reagent cavity. The reagent carrying portion 3 and the carrier 4 may be an integrated structure. When nucleic acid amplification is performed, the thickness direction of the carrier 4 is aligned with the vertical direction along the direction indicated by the arrow in FIG. 16 . Inserted between two external heaters 200 or other structures required for amplification (such as a cooling mechanism 201 for cooling the reaction sample), this can ensure that the opening of the cavity in the reagent carrying part 3 faces upward, and when a sealing film 34 is not set on the opening, it can still prevent the residual solution in the cavity from dripping and causing contamination.

However, since the sample holding cavity 41 and/or the carrier 4 are flat structures, bubbles often penetrate the thickness direction of the sample holding cavity 41, so that the bubbles are easily arranged opposite to the detection unit 203 located on the side of the carrier 4, thereby causing inaccurate detection results.

To avoid the above problems, optionally, the reagent carrying part 3 and the carrier 4 are split structures, and then the carrier 4 can be inserted between two external heaters 200 or other structures required for amplification (such as the cooling mechanism 201 for cooling the reaction sample as shown in Figure 4) according to the orientation requirements, such as the carrier 4 is vertically inserted (hereinafter referred to as vertical insertion of the carrier 4) in the thickness direction (Y direction as shown in Figure 17) and the vertical direction (Z direction as shown in Figure 17, the X, Y and Z directions are perpendicular to each other) between the two external heaters 200 or other structures required for amplification (such as the cooling mechanism 201 for cooling the reaction sample).

Alternatively, the reagent carrying part 3 and the carrier 4 are detachably connected, such as being able to separate the reagent carrying part 3 and the carrier 4 from the connection between the reagent carrying part 3 and the carrier 4. Furthermore, if a plurality of spaced holes are provided between the connection between the carrier 4 and the reagent carrying part 3, the holes can be conveniently broken between the carrier 4 and the reagent carrying part 3. After the carrier 4 is independent, the carrier 4 can be vertically inserted between two external heaters 200 or other structures required for amplification (such as a cooling mechanism 201 for cooling the reaction sample).

Alternatively, the reagent carrying portion 3 is connected to the carrier 4, and the angle between the reagent carrying portion 3 and the carrier 4 is adjustable, such as the carrier 4 and the reagent carrying portion 3 can be bent. If a groove is provided between the carrier 4 and the reagent carrying portion 3, the carrier 4 or the reagent carrying portion 3 can be bent along the groove. As shown in FIG17 , after the carrier 4 or the reagent carrying portion 3 is bent, 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 the reaction sample) along the direction indicated by the arrow in FIG17 , and when the carrier 4 is inserted, the opening of the reagent chamber faces upward, and the reagent in the reagent chamber does not drip.

As shown in Figure 18, preferably, the thickness direction of the sample holding cavity 41 or the carrier 4 (the X direction as shown in Figure 18) is perpendicular to the depth direction of the reagent cavity (the Z direction as shown in Figure 18, the X, Y and Z directions are perpendicular to each other). In this way, when the carrier 4 and the reagent carrying part 3 are an integrated structure, and the relative position between the carrier 4 and the reagent carrying part 3 does not change, the carrier 4 can also be vertically inserted into the two external heaters 200 or other structures required for amplification (such as a cooling mechanism 201 for cooling the reaction sample) along the direction indicated by the arrow in Figure 18. In this way, it can be ensured that the opening of the cavity in the reagent carrying part 3 is facing upward, and the bubbles can also float to the top of the carrier 4.

As shown in FIG. 19a , the heater 45 includes a heating element 451. A power source is connected to the heating element 451. The controllable heating source inside the heater 45 can be a resistor, such as a copper material made into a resistor thin wire structure, and 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 use a coil structure or use ferromagnetic materials to perform electromagnetic induction heating.

As shown in Figure 19a, preferably, heater 45 comprises at least two independently controlled heating elements 451, and heating element 451 can be independently controlled to improve the uniformity of reaction sample temperature. As, if the temperature of a heating element 451 does not reach the preset temperature (how to detect the temperature of heating element 451 is described in detail below), the electric current of this heating element 451 is increased, and reaction sample is quickly raised to the preset temperature. In the present embodiment, because heater 45 is in direct contact with the reaction sample in carrier 4, the thermal conductivity between heater 45 and reaction sample is high, and the temperature of the heating element 451 of heater 45 can be equal to the temperature of reaction sample, therefore, the temperature of each heating element 451 is controlled to reach the preset temperature, and reaction sample everywhere can be made to be in the preset temperature, and then the reaction sample temperature uniformity is guaranteed.

As shown in Fig. 19a, the heater 45 may further include an upper conductive component 92 and a lower conductive component 95, and the heating element 451 is sandwiched between the upper conductive component 92 and the lower conductive component 95. The upper conductive component 92 and the lower conductive component 95 have heat conduction and insulation functions.

The heater 45 includes a heat-averaging layer 921. Specifically, the upper conductive component 92 may also include a heat-averaging layer 921. The heat-averaging layer 921 is in direct contact with the reaction sample in the accommodating cavity 41. The heat-averaging layer 921 can ensure uniform conduction of heat in both the longitudinal and transverse directions (i.e., the thickness direction of the reaction sample and the surface perpendicular to the thickness direction), thereby ensuring the temperature uniformity of the sample liquid. Optionally, the heat-averaging layer 921 is made of an insulating material, such as an insulating material such as a high thermal conductivity ceramic.

The heat-dissipating layer 921 is made of insulating material and is adjacent to the heating element 451 . This can reduce the number of layers of the carrier 4 , shorten the time for the heat of the heating element 451 to be transferred to the reaction sample in the carrier 4 , and shorten the time required for the carrier 4 to dissipate heat.

As shown in Figure 19a, the lower conduction component 95 also includes an insulating thermal resistance layer 951. The insulating thermal resistance layer 951 has certain thermal resistance characteristics and insulation characteristics. 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 through material selection and thickness selection to meet different design requirements. For example, a thin layer with a thickness of 0.1-0.3mm can be used, and the thermal conductivity of the material is selected in the range of 0.2 to 0.5W/mK. Usually, the thermal resistance of this layer is much greater than the thermal resistance of other layers of the structure, so the edge thermal resistance layer is the main source of thermal resistance for the carrier 4 to dissipate heat and cool down the cooling mechanism 201. The insulating thermal resistance layer 951 is one of the main factors affecting the thermal properties of the carrier 4.

Optionally, the lower conductive component 95 further includes a heat conductive layer 952, which is located far away from the insulating thermal resistance layer 951. The side away from the heating element 451. Furthermore, the heat-conducting layer 952 is the outermost layer of the lower conductive component 95, which is in direct contact with the cooling mechanism 201. The heat-conducting layer 952 is made of metal such as copper or other materials with high thermal conductivity. Due to cost control or processing technology limitations, it is difficult to avoid point contact between the surface of the lower conductive component 95 and the cooling mechanism 201. When the outermost layer of the lower conductive component 95 is the heat-conducting layer 952, even if the heat-conducting layer 952 is in point contact with the cooling mechanism 201, the heat-conducting layer 952 can also distribute the heat evenly throughout the heat-conducting layer 952 due to its good conductivity, thereby evenly distributing the heat of other layers of the lower conductive component 95.

Preferably, the heating element 451 of this embodiment is a resistor, and there is a specific relationship between the resistor and its temperature. Therefore, 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 deduced through the resistance temperature coefficient and the nominal resistance value. The temperature reflects the current temperature of the carrier 4 in real time without delay, so it can be used for rapid feedback control of the carrier 4 and the reaction sample temperature. Compared with the prior art, the sample temperature can be controlled more accurately and the overall response speed of the temperature control system can be improved.

In order to detect the resistance of the heating element 451, the carrier 4 may further include a second contact 96, which is configured for a resistance detection element to detect the resistance of the heating element 451, so as to measure the temperature of the heating element 451 by a resistance temperature measurement method. The resistance detection element may include a terminal, etc., which is in contact with and electrically connected to the second contact 96, so as to detect the voltage U and the current I of the heating element 451 through the second contact 96, and then obtain the resistance R (R=U/I).

However, the disadvantage of the resistance temperature measurement method is that for the same type of resistors, such as copper wire resistors, there are slight differences in the nominal resistance value and the resistance temperature coefficient (the resistance value at the nominal temperature is referred to as the nominal resistance value, and the nominal resistance means that at this temperature, the declared (or marked) resistance value is true, where this temperature is the nominal temperature, and the nominal temperature can be selected arbitrarily according to needs) between the resistors, resulting in a slight difference between the actual resistance temperature coefficient of a single heating element 451 and the nominal resistance value, which may cause temperature measurement errors. Therefore, preferably, as shown in FIG19a, the carrier 4 also includes a temperature detection unit 99 configured to detect the temperature of the carrier 4, and the temperature detection unit 99 may include 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 very quickly 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. Therefore, under normal circumstances, the detection result measured by the temperature detection unit 99 will have a temperature measurement delay of 1 to 2 seconds. In the process of rapid temperature rise and fall, the temperature change of the carrier 4 can reach more than 30°C within 1-2 seconds. Therefore, in the process of rapid temperature rise and fall, it is relatively difficult to control the carrier 4 through the temperature detection unit 99. This embodiment controls the carrier 4 through a dual temperature measurement method of resistance temperature measurement and calibration of the temperature of the carrier 4 through the temperature detection unit 44.

This embodiment does not completely rely on the temperature value measured by the uncalibrated resistance temperature measurement method, nor does it completely The temperature control carrier 4 is not dependent on the temperature detected by the temperature detection unit 99, but by combining the two, the temperature detection unit 99 is used to measure the temperature of the carrier 4 and the resistance temperature measurement method is used to measure the temperature of the heating element 451, so that the temperature of the carrier 4 can be quickly and accurately controlled to achieve the purpose of accurate temperature control, thereby overcoming the problems of temperature detection delay and large temperature measurement error caused by the temperature detection method commonly used in the prior art.

In order to more clearly illustrate how to use the temperature detection unit 99 in this embodiment to calibrate the temperature detected by the resistance detection element, FIG. 19b shows a process of calibrating the resistance temperature measurement method by the temperature detection unit 99 in an actual test. Before calibrating the temperature value, an initial RT temperature curve, i.e., a preset temperature curve, is preset, and then a very small current is applied to the heating element 451 of the carrier 4, such as a current of less than 1 mA. The purpose of applying a very small current is to read the resistance of the heating element 451 without causing the heating element 451 to heat up.

First calibration: the temperature detection unit 99 measures the first temperature calibration value T ₁ , and the resistance detection unit detects the first voltage U ₁ and the first current I ₁ of the heating element 451 at temperature T ₁ , and the resistance R ₁ of the heating element 451 at temperature T ₁ can be obtained according to R=U/I.

Second calibration: The temperature detection unit 99 then measures a second temperature calibration value T ₂ , and the resistance detection unit detects a second voltage U ₂ and a second current I ₂ of the heating element 451 at temperature T ₂ , and the resistance R ₂ of the heating element 451 at temperature T ₂ can be obtained according to R=U/I.

Finally, according to two sets of two-variable linear equations: R ₁ =R ₀ (1+αΔT ₁ ) and R ₂ =R ₀ (1+αΔT ₂ ), (wherein, ΔT ₁ =T ₁ -T ₀ , ΔT ₂ =T ₂ -T ₀ , T ₁ is the resistance value of the heating element 451 corresponding to the temperature T ₁ , T ₂ is the resistance value of the heating element 451 corresponding to the temperature T ₂ , α is the resistance temperature coefficient of the material, T ₀ is the nominal temperature, and R ₀ is the nominal resistance value), the specific values of R ₀ and α are obtained, that is, the accurate RT curve is obtained, and subsequently the temperature of the heating element 451 measured by the resistance temperature measurement method can be used as feedback for accurate temperature control.

The temperature calibration value can be detected throughout the entire process of nucleic acid amplification, so the temperature can be calibrated multiple times in the subsequent process to further improve the detection accuracy.

As shown in FIG. 19a, the heater 45 provided in this embodiment further includes a temperature calibration portion 93 configured to reflect the temperature of the heating element 451. The temperature detection unit 99 detects the temperature of the heater 45 through the temperature calibration portion 93. The temperature calibration portion 93 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 independently controlled, each heating element 451 is correspondingly provided with a temperature detection unit 99, a second contact 96 and a temperature calibration portion 93 to calibrate the heating element 451 respectively.

As shown in FIG. 19c, when the temperature detection unit 99 is a contact temperature sensor, in order to facilitate the temperature detection unit 99 to measure the temperature, the two first contacts of the temperature detection unit 99 are respectively in contact with the two temperature calibration parts 93, and the two temperature calibration parts 93 are not conductive. At this time, the heater 45 may also include an external electrical connection. Contact points 97 and electrical connection leads 98, the number of external electrical connection contacts 97 and electrical connection leads 98 can be two each, the two external electrical connection contacts 97 are respectively located on the side of the two temperature calibration parts 93 away 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.

As shown in FIG19a , the temperature of the heat-dissipating layer 921 of the upper conduction component 92 is conducted to the temperature calibration part 93, and the temperature calibration part 93 is electrically connected to the external resistance detection part at the external electrical connection contact 97 through the electrical connection lead 98. For example, the external resistance detection part can detect the resistance of the first temperature detection unit 99 through the external electrical connection contact 97, and then obtain the temperature of the first temperature detection unit 99 based on the resistance. Optionally, the diameter of the electrical connection lead 98 is smaller than that of the temperature calibration part 93 and the external electrical connection contact 97, thereby reducing the heat loss generated by the temperature calibration part 93 through the electrical connection lead 98, so that the temperature calibration part 93 can better reflect the temperature of the upper conduction component 92, such as the temperature of the heat-balancing layer 921 of the upper conduction component 92, and the temperature detection unit 99 achieves good electrical and thermal contact with the temperature calibration part 93 through the solder joint. When the temperature of the upper conduction component 92, such as the heat-balancing layer 921 of the upper conduction component 92 changes, the temperature detection unit 99 can quickly and accurately sense the temperature change. The temperature change causes the resistance value of the temperature detection unit 99 to change. The resistance value change of the temperature detection unit 99 is detected in real time at the external electrical connection contact 97, thereby achieving real-time temperature detection.

As shown in FIG. 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, optionally, the carrier 4 may further include a fast conduction part 94, and the fast conduction part 94 is configured to conduct 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, such as the heating element 451 heats the heat-isolating layer 921, and the heat of the heat-isolating layer 921 is conducted to the temperature calibration part 93 through the fast conduction part 94, thereby, the temperature calibration part 93 accurately reflects the temperature of the heat-isolating layer 921, and then the temperature detection unit 99 can accurately measure the temperature of the heat-isolating 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-isolating layer 921, so the temperature of the reaction sample can be obtained by detecting the temperature of the temperature calibration part 93.

Preferably, one side of the fast conduction part 94 is connected to one side of the upper conduction component 92 close to the heating element 451 or to one side of the lower conduction component 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 component 92 and the upper surface of the lower conduction component 95 are closest to the heating element 451, and their temperatures are first close to the temperature of the heating element 451. Therefore, the arrangement of the fast conduction part 94 can make the temperature of the fast conduction part 94 and the temperature of the heating element 451 consistent in the shortest time. Optionally, the fast conduction part 94 is made of a material with high thermal conductivity, such as a metal material such as copper or aluminum, or a thermally conductive ceramic. The thermal conductivity of the fast conduction part 94 is particularly better than that of the lower conduction component 95, so as to quickly transfer heat to the temperature calibration part 93.

The fast conducting part 94 includes a patch 941 and one or more guide pillars 942. The patch 941 and the upper conducting component 92 The side close to the heating element 451 is in contact with the side close to the heating element 451 of the lower conduction component 95, and one end of one or more guide pillars 942 is connected to the patch 941, and the other end is passed through the lower conduction component 95 and connected to the temperature calibration part 93. The lower surface of the upper conduction component 92 and the upper surface of the lower conduction component 95 are closest to the heating element 451, and their temperatures are the first to approach the temperature of the heating element 451. Therefore, the arrangement of the patch 941 can make the temperature of the fast conduction part 94 consistent with the temperature of the heating element 451 as quickly as possible. The patch 941 can increase the contact area between the fast conduction part 94 and the upper conduction component 92 or the lower conduction component 95, and improve the conduction efficiency. The cross-sectional area of the guide pillar 942 can be smaller than the cross-sectional area of the patch 941, and the temperature of the patch 941 can be quickly conducted to the temperature calibration part 93, ensuring that the thermal resistance layer generates the required thermal resistance as designed. Optionally, patch 941 and guide pillar 942 are made of materials with high thermal conductivity such as copper. When patch 941 and guide pillar 942 are required to be insulating materials to avoid short circuit of carrier 4, patch 941 or guide pillar 942 can be made of materials such as high thermal conductivity ceramics.

It is understandable that the temperature calibration part 93 can be arranged in a one-to-one correspondence with 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 guide post 942, and in order to improve the temperature uniformity of the temperature calibration part 93, the temperature calibration part 93 can also be connected to multiple guide posts 942.

As shown in FIG19a, in order to obtain the resistance of the heating element 451 and to supply power to the heating element 451, optionally, a second contact 96 is provided on the outer surface of the carrier 4, a plurality of second contacts 96 are provided, 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 then the resistance value of the heating element 451 can be obtained.

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

Embodiment 2

As shown in Figures 20a to 22, the carrier of this embodiment 2 is basically the same as the above-mentioned embodiment 1. The difference between the two is that in this embodiment, the carrier 4 is not provided with an extrusion cavity 46, and an external heater 200 is provided on the outer side of the first wall 43 and/or the second wall 44 of the carrier 4 to heat the reaction sample in the carrier 4.

As shown in FIG20a, the carrier 4 further includes a drainage portion, which includes a drainage cavity 410, and the reaction sample in the sample holding cavity 41 can be transferred to the drainage 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 provided between the drainage cavity 410 and the sample holding cavity 41.

As shown in FIG. 20a, the sample holding chamber 41 does not carry the reaction sample, and the carrier 4 is in an empty state; optionally, when the first wall 43 and the second wall 44 are connected to the side wall 42, the first wall 43 and/or the second wall 44 are not tightened, so that, as shown in FIG. 20b, when the sample holding chamber 41 is filled with the reaction sample, the first wall 43 and/or the second wall 44 are not tightened. 43 and/or the second wall 44 protrude outward, and the carrier 4 is in a fully loaded state. At this time, since the one-way valve, the two-way valve or the film stops the reaction sample in the sample holding chamber 41 from entering the drainage chamber 410, the drainage chamber 410 is not filled with the reaction sample. As shown in Figure 21, the first wall 43 and/or the second wall 44 are made of a deformable material, such as an aluminum film or an aluminum film and a pp film. When the external heater 200 presses down the carrier 4, the first wall 43 and/or the second wall 44 are deformed and close to each other, and the surface of the first wall 43 and/or the second wall 44 changes from an arc to a plane, so that the external heater 200 is closely attached to the first wall 43 and/or the second wall 44 of the carrier 4, and then the entire first wall 43 and/or the second wall 44 corresponding to the sample holding chamber 41 is heated, the volume of the sample holding chamber 41 is reduced, the pressure is increased, the one-way valve or the two-way valve is opened, or the film is broken, so that part of the reaction sample in the carrier 4 is transferred to the drainage chamber 410, and the carrier 4 is in a pressure relief state. That is, the drainage cavity 410 can accommodate the excess reaction sample in the accommodating cavity 41, so that the first wall 43 and/or the second wall 44 no longer protrude outward, so that the external heater 200 heats the entire first wall 43 and/or the second wall 44 corresponding to the accommodating cavity 41, thereby improving the amplification efficiency. Since the carrier 4 is full of reaction samples, the reaction samples are also closely attached to the first wall 43 and/or the second wall 44, thereby ensuring the heat conduction efficiency between the external heater 200 and the reaction samples. At the same time, when the carrier 4 is converted from a fully loaded state to a pressure relief state, the thickness of the sample accommodating cavity 41 is reduced, which can further improve the heat equalization speed of the reaction samples in the sample accommodating cavity 41.

Although Figure 20b only shows that one of the first wall 43 and the second wall 44 bulges outward, at this time, the other of the first wall 43 and the second wall 44 is rigid and cannot be deformed or its deformability is smaller than the deformation capacity of the first wall 43 or the second wall 44 that bulges outward, but those skilled in the art will understand that both the first wall 43 and the second wall 44 may be deformed so as to bulge outward. At this time, there are external heaters 200 on both 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 squeeze the carrier 4, so that the first wall 43 and the second wall 44 are deformed, and the surfaces of the first wall 43 and the second wall 44 change from arc to plane, so that the external heaters 200 are in close contact with the first wall 43 and the second wall 44 of the carrier 4.

Optionally, the volume of the drainage chamber 410 is fixed, and when squeezed, the liquid in the sample holding chamber 46 is transferred to the drainage chamber 410 and fills the drainage chamber 410 , thereby facilitating the quantification of the reaction sample added to the carrier 4 .

If during the amplification stage, the external heater 200 continues to contact the carrier 4, the reaction sample entering the drainage portion does not need to be transferred to the carrier 4. At this time, optionally, a one-way valve is provided between the drainage chamber 410 and the sample holding chamber 41. When the sample holding chamber 41 is squeezed by the external heater 200, the pressure in the sample holding chamber 41 increases, the one-way valve opens, and the reaction sample enters the drainage chamber 410.

As shown in FIG. 21 and FIG. 22, if the external heater 200 is intermittently separated and contacted with the carrier 4 during the amplification stage, after the external heater 200 is separated from the carrier 4, the liquid discharge unit transfers the reaction sample to the carrier 4. A two-way valve may be provided between the liquid cavity 410 and the sample holding cavity 41. When the pressure in the sample holding cavity 41 increases due to being squeezed, the two-way valve opens, and the reaction sample enters the liquid discharge cavity 410. When the external heater 200 is separated from the carrier 4, the two-way valve may be opened by squeezing the liquid discharge portion, thereby allowing the reaction sample in the liquid discharge cavity 410 to enter the sample holding cavity 41. Alternatively, in other optional embodiments, a thin film may be provided between the liquid discharge cavity 410 and the sample holding cavity 41. For example, the thin film may be a PDMS thin film, and the thickness of the PDMS thin film may be several microns to more than ten microns, such as a 15 um PDMS thin film. When the sample holding cavity 41 is squeezed by the external heater 200, the thin film ruptures, and the reaction sample may enter the liquid discharge cavity 410. When the external heater 200 is separated from the carrier 4, the liquid discharge portion may be squeezed, thereby allowing the reaction sample in the liquid discharge cavity 410 to enter the sample holding cavity 41. It is understandable that the thickness of the film is smaller than the thickness of the first wall 43 and the second wall 44 to prevent the first wall 43 and the second wall 44 from being ruptured when the film is ruptured.

Claims (35)

A carrier comprises a first wall (43) and a second wall (44) arranged opposite to 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) form a sample holding cavity (41); the sample holding cavity (41) is a flat structure, and at least a portion of the side wall (42) is light-transmissive. The carrier according to claim 1, wherein the first wall (43) and/or the second wall (44) is a film (409) made of a thermally conductive material. The carrier according to claim 1, wherein the first wall (43) and/or the second wall (44) is a heater (45), and the heater (45) is configured to heat the reaction sample in the sample holding cavity (41). The carrier according to claim 1, wherein the carrier is a flat structure. The carrier according to claim 1, wherein the carrier further comprises an extrusion cavity (46), wherein the extrusion cavity (46) is deformed under an external force so as to cause the sample holding cavity (41) to be deformed. The carrier according to claim 5, wherein the carrier comprises an extrusion area (47) and an amplification area (48), the extrusion chamber (46) is arranged in the extrusion area (47), and the sample holding chamber (41) is arranged in the amplification area (48). The carrier according to claim 6, wherein the first wall (43) and the second wall (44) corresponding to the pressing area (47) are formed of a deformable material. The carrier according to claim 7, wherein the extrusion chamber (46) and the sample holding chamber (41) are connected, or the extrusion chamber (46) and the sample holding chamber (41) are separated by an elastic membrane (49). The carrier according to claim 6, wherein the extrusion zone (47) has an air inlet, the air inlet is provided with an air inlet portion, and the air inlet portion is configured to control the gas to enter the extrusion chamber (46). A carrier according to claim 1, wherein the first wall (43) and the second wall (44) are made of an aluminum film; or the first wall (43) and the second wall (44) are made of an aluminum film and an isolation film, and the isolation film is connected to a side of the aluminum film close to the sample holding cavity (41). The carrier according to claim 5, wherein the carrier further comprises a first liquid inlet (401) and a first exhaust hole (402) connected to the sample holding cavity (41). The carrier according to claim 11, wherein the first liquid inlet (401), the extrusion chamber (46), the sample holding chamber (41) and the first exhaust hole (402) are connected in sequence through a first channel (403). The carrier according to claim 12, wherein the extrusion chamber (46), the first liquid inlet The port (401) and the first exhaust hole (402) are both arranged on the same side of the sample holding chamber (41). The carrier according to claim 13, wherein the extrusion chamber (46) and the first liquid inlet (401) are located directly above the sample holding chamber (41), the first exhaust hole (402) is located above the side of the sample holding chamber (41), and one end of the first channel (403) is connected to the lower end of the sample holding chamber (41), and the other end is connected to the first exhaust hole (402); or The first exhaust hole (402) is located directly above the sample holding cavity (41), the extrusion cavity (46) and the first liquid inlet (401) are located on the upper side of the sample holding cavity (41), and one end of the first channel (403) is connected to the lower end of the sample holding cavity (41), and the other end is connected to the extrusion cavity (46). According to the carrier of claim 12, wherein the first liquid inlet (401) and the extrusion chamber (46) are arranged on one side of the sample holding chamber (41), the first exhaust hole (402) is arranged on the other side of the sample holding chamber (41), and one side of the sample holding chamber (41) and the other side of the sample holding chamber (41) are opposite to each other. The carrier according to claim 1, wherein the carrier further comprises a second liquid inlet (404) and a second exhaust hole (405) connected to the sample holding cavity (41), and the second liquid inlet (404), the sample holding cavity (41) and the second exhaust hole (405) are connected in sequence through a second channel (406). The carrier according to claim 16, wherein the second liquid inlet (404) and the second exhaust hole (405) are located on the same side of the sample holding cavity (41), or on opposite sides of the sample holding cavity (41). The carrier according to claim 11 or 16, wherein the liquid inlet and/or the exhaust hole is sealed by a sealing cover (407), a thermoplastic seal, a pressure-sensitive adhesive or a plug, or the exhaust hole is provided with an air-permeable and water-impermeable membrane. According to any one of claims 1-4 or 10, the carrier further comprises a drainage portion, the drainage portion comprises a drainage cavity (410), and the reaction sample in the sample holding cavity (41) can be transferred to the drainage cavity (410). The carrier according to claim 19, wherein a one-way valve, a two-way valve or a film is provided between the drainage cavity (410) and the sample holding cavity (41). The carrier according to claim 1, wherein the first wall (43) and the second wall (44) are made of a deformable material. The carrier according to claim 3, wherein the heater (45) comprises a heating element (451), and the number of the heating element (451) is at least one. The carrier according to claim 22, wherein the number of the heating elements (451) is at least two, and at least two of the heating elements (451) are independent of each other. The carrier according to claim 22, wherein the carrier further comprises a temperature detection unit (99) configured to detect a temperature of the carrier. The carrier according to claim 24, wherein the heater (45) further comprises a temperature calibration portion (93) configured to reflect the temperature of the heating element (451), and the temperature detection unit (99) is configured to detect the temperature of the temperature calibration portion (93). The carrier according to claim 25, wherein the heater (45) further comprises a fast conduction portion (94), and the fast conduction portion (94) is configured to conduct heat of the heating element (451) to the temperature calibration portion (93). A carrier according to any one of claims 22 to 26, wherein the carrier may further include a second contact (96), wherein the second contact (96) is configured for a resistance detection element to detect the resistance of the heating element (451). The carrier according to claim 1, wherein the flat structure refers to that the dimension of the sample holding cavity (41) or the carrier in a direction perpendicular to its thickness direction is larger than its dimension in the thickness direction. The carrier according to claim 28, wherein the ratio of the dimension of the sample holding cavity (41) or the carrier in a direction perpendicular to its thickness direction to its thickness direction is greater than 5:1. The carrier according to claim 29, wherein the size ratio is 50:1 to 100:1. A reagent kit comprises a reagent carrying portion (3) and a carrier (4) according to any one of claims 1 to 30, wherein the reagent carrying portion (3) is at least configured to carry a reagent. The kit according to claim 31, wherein the reagent carrying portion (3) and the carrier (4) are an integrated structure; or The reagent carrying part (3) and the carrier (4) are of separate structures; or The reagent carrying portion (3) is detachably connected to the carrier (4); or The reagent carrying part (3) is connected to the carrier (4), and the angle between the reagent carrying part (3) and the carrier (4) is adjustable. The reagent kit according to claim 31, wherein the reagent carrying portion (3) comprises at least one pre-set reagent chamber (31). The kit according to claim 33, wherein the agent-carrying portion (3) further comprises at least one injection cavity (32) and/or at least one cavity (33). The kit according to claim 31, wherein the sample holding chamber (41) or the carrier The thickness direction of the body (4) is parallel or perpendicular to the depth direction of the cavity of the agent carrying portion (3).