Temperature control device for PCR (Polymerase Chain Reaction) analyzer and PCR analyzer

Abstract

The utility model relates to a temperature control device for a PCR (Polymerase Chain Reaction) analyzer and the PCR analyzer. The temperature control device comprises a fixing seat, a temperature control part, a first heat insulation assembly, a heat conduction part and a second heat insulation assembly, the temperature control part is connected to the upper side of the fixing seat, one side of the first heat insulation assembly is connected to the fixing seat, and the other opposite side of the first heat insulation assembly is attached to the temperature control part, so that heat generated by the temperature control part is not easily transmitted to the fixing seat; therefore, the heat energy loss can be reduced, the temperature control device can quickly reach the required reaction temperature, and the test efficiency of the PCR reaction is improved; the heat conduction part is attached to the upper side of the temperature control part and used for bearing the sample carrying frame and conducting heat generated by the temperature control part to the sample carrying frame, and the second heat insulation assembly is attached to the upper side of the heat conduction part, so that the temperature of the sample carrying frame can be prevented from rising or falling too fast, and the temperature uniformity of the sample carrying frame is guaranteed; and the temperature control device is further ensured to quickly reach the required reaction temperature.

Description

Technical Field

[0001] This application relates to the field of biological detection technologies, and particularly to a temperature control device for a PCR analyzer and a PCR analyzer. Background Art

[0002] Polymerase chain reaction (PCR) is a molecular biology technique used to amplify specific DNA fragments, which can be regarded as a special DNA amplification in vitro. This technique can greatly increase trace gene fragments. A PCR analyzer (gene amplifier) is a gene amplification instrument that uses PCR technology for gene analysis applications.

[0003] When a PCR analyzer is running, a sample reagent needs to be inserted into a temperature control device at a constant temperature to sequentially perform steps of high-temperature denaturation, medium-temperature pairing and replication, and appropriate-temperature extension, so as to achieve the amplification of gene fragments. Therefore, in a PCR analyzer, the temperature of the temperature control device needs to be maintained at the required reaction temperature at all times to ensure the final accuracy of the PCR reaction. However, in traditional PCR analyzers on the market at present, the temperature control device is mostly composed of a heating plate, a temperature sensor, and a fan radiator. During the PCR reaction process, the heating and cooling processes required can only be controlled by the temperature control system to repeatedly heat and cool a fixed heating plate. This traditional heating and cooling mode not only takes a long time, but also easily shows the phenomenon of "overshoot" due to the reaction time difference of the temperature sensor, resulting in the inability to quickly reach the required reaction temperature, and thus the test efficiency of existing PCR analyzers is relatively low. Summary of the Utility Model

[0004] Based on this, the purpose of this application is to provide a temperature control device for a PCR analyzer and a PCR analyzer including the temperature control device, so as to solve the problem that the temperature control device of the existing PCR analyzer cannot quickly reach the required reaction temperature, and thus the test efficiency of the existing PCR analyzer is relatively low.

[0005] According to one aspect of this application, there is provided a temperature control device for a PCR analyzer, characterized in that the temperature control device includes:

[0006] A fixed seat;

[0007] A temperature control member, connected to the upper side of the fixed seat, and the temperature control member is used to generate heat;

[0008] A first heat insulation assembly, provided between the fixed seat and the temperature control member, with one side of the first heat insulation assembly connected to the fixed seat and the opposite side fittingly connected to the temperature control member;

[0009] A heat conducting member is disposed on the upper side of the temperature control member. The heat conducting member is used to carry the sample carrier and conduct the heat generated by the temperature control member to the sample carrier.

[0010] A second heat insulation assembly is disposed on the upper side of the heat conducting member. The second heat insulation assembly is used to keep the sample carrier thermally insulated.

[0011] In one embodiment, the first heat insulation assembly includes a first heat insulation cotton and a plurality of heat insulation balls connected to the first heat insulation cotton and arranged at intervals. The first heat insulation cotton is spaced from the fixed seat and is connected to the fixed seat by a plurality of the heat insulation balls at points.

[0012] In one embodiment, the material of the first heat insulation cotton is an aerogel material.

[0013] In one embodiment, the heat conducting member is provided with a plurality of jacks arranged in an array. The second heat insulation assembly includes a heat insulation protective cover and a second heat insulation cotton. Both the heat insulation protective cover and the second heat insulation cotton are provided with a plurality of through holes penetrating through opposite sides of themselves and arranged in an array. The jacks and the through holes correspond to each other one by one, and the jacks and the through holes respectively correspond to a plurality of PCR tubes of the sample carrier. Each through hole is used for a corresponding PCR tube to pass through, and each jack is used for a corresponding PCR tube to be inserted.

[0014] In one embodiment, a plurality of optical fiber connectors are provided on the lower side of the fixed seat. All the optical fiber connectors and all the jacks correspond to each other one by one, and each optical fiber connector is used to connect to an optical fiber.

[0015] In one embodiment, the optical fiber connector is detachably connected to the fixed seat.

[0016] In one embodiment, a plurality of magnets arranged in an array are embedded in the heat conducting member. Any one magnet is disposed between two adjacent jacks. The magnet is configured to adsorb the magnetic beads to the wall of the PCR tube when the heat conducting member carries the sample carrier and there are magnetic beads in the sample in the sample carrier.

[0017] In one embodiment, the second heat insulation assembly includes a second heat insulation cotton and a heat insulation protective cover. The heat insulation protective cover is disposed on one side of the second heat insulation cotton in its thickness direction. The side of the second heat insulation cotton facing away from the heat insulation protective cover is attached to the heat conducting member.

[0018] In one embodiment, the temperature control member includes a substrate and a heating element. The heating element is disposed in the substrate according to the heating distribution of the temperature control member.

[0019] According to another aspect of the present application, a PCR analyzer is provided, which includes an optical detection device and a temperature control device as described in any of the above solutions, and the optical detection device is connected to the fixed seat of the temperature control device through an optical fiber.

[0020] For the temperature control device for the PCR analyzer and the PCR analyzer as described above, on the one hand, by arranging a first heat insulation component between the fixed seat and the temperature control element, the heat generated by the temperature control element is not easily transmitted to the fixed seat, so that the heat energy loss can be reduced, ensuring that the temperature control device can quickly reach the required reaction temperature and improving the test efficiency of the PCR reaction; on the other hand, by arranging a second heat insulation component on the upper side of the heat conducting member, when the heat conducting member carries the sample carrier, the second heat insulation component can be located between the heat conducting member and the sample carrier, thereby preventing the influence of the ambient temperature on the heat conducting member, playing a role of heat preservation and insulation, ensuring the temperature uniformity of the heat conducting member and further ensuring the temperature uniformity of the sample carrier, and further ensuring that the temperature control device can quickly reach the required reaction temperature. Description of the Drawings

[0021] Figure 1 Is an axonometric view of the temperature control device provided by an embodiment of the present application.

[0022] Figure 2 Is an exploded view of the temperature control device provided by an embodiment of the present application.

[0023] Figure 3 Is a cross-sectional view of the temperature control device provided by an embodiment of the present application.

[0024] Figure 4 Is Figure 3 An enlarged schematic view of area A in

[0025] Figure 5 Is an axonometric view of the sample carrier provided by an embodiment of the present application Figure 1 .

[0026] Figure 6 Is an axonometric view of the sample carrier provided by an embodiment of the present application Figure 2 .

[0027] Description of the Reference Numerals:

[0028] 10. Temperature control device; 110. Fixed seat; 120. First heat insulation component; 121. First heat insulation cotton; 122. Heat insulation ball; 130. Temperature control element; 140. Heat conducting member; 141. Jack; 150. Second heat insulation component; 151. Heat insulation protective cover; 152. Second heat insulation cotton; 160. Optical fiber connector; 170. Inductive element; 20. Sample carrier; 21. PCR tube; 22. Accommodating cavity; 30. Optical fiber. Detailed Description of the Embodiment

[0029] To make the above objects, features, and advantages of the present application more apparent and understandable, the following provides a detailed description of the specific embodiments of the present application in conjunction with the accompanying drawings. Many specific details are set forth in the following description to facilitate a full understanding of the present application. However, the present application can be implemented in many other ways different from those described herein, and those skilled in the art can make similar improvements without departing from the connotation of the present application. Therefore, the present application is not limited by the specific embodiments disclosed below.

[0030] In the description of the present application, it should be understood that if terms such as "center", "longitudinal", "transverse", "length", "width", "thickness", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", "clockwise", "counterclockwise", "axial", "radial", "circumferential", etc. appear, the orientation or positional relationship indicated by these terms is based on the orientation or positional relationship shown in the accompanying drawings, and is only for the convenience of describing the present application and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be construed as a limitation to the present application.

[0031] In addition, if terms such as "first" and "second" appear, these terms are only for descriptive purposes and should not be construed as indicating or implying relative importance or implicitly specifying the quantity of the indicated technical features. Thus, features defined with "first" and "second" may explicitly or implicitly include at least one such feature. In the description of the present application, if the term "plurality" appears, the meaning of "plurality" is at least two, such as two, three, etc., unless otherwise specifically and clearly defined.

[0032] In the present application, unless otherwise clearly specified and limited, if terms such as "mounted", "connected", "coupled", "fixed", etc. appear, these terms should be understood in a broad sense. For example, it can be a fixed connection, a detachable connection, or integrated; it can be a mechanical connection or an electrical connection; it can be directly connected or indirectly connected through an intermediate medium, and it can be the communication inside two elements or the interaction relationship between two elements, unless otherwise clearly limited. For those of ordinary skill in the art, the specific meanings of the above terms in the present application can be understood according to specific circumstances.

[0033] In this application, unless otherwise clearly specified and defined, when a first feature is described as being "on" or "under" a second feature or similar descriptions, it may mean that the first and second features are in direct contact, or the first and second features are in indirect contact through an intermediate medium. Moreover, the first feature being "above", "over" and "on top of" the second feature may mean that the first feature is directly above or obliquely above the second feature, or simply indicates that the first feature has a higher horizontal height than the second feature. The first feature being "under", "beneath" and "underneath" the second feature may be that the first feature is directly below or obliquely below the second feature, or simply indicates that the first feature has a lower horizontal height than the second feature.

[0034] It should be noted that if an element is referred to as being "fixed to" or "disposed on" another element, it can be directly on the other element or there may also be an intermediate element. If an element is considered to be "connected" to another element, it can be directly connected to the other element or there may be an intermediate element at the same time. If so, the terms "vertical", "horizontal", "up", "down", "left", "right" and similar expressions used in this application are only for the purpose of illustration and do not represent the only implementation.

[0035] This application provides a temperature control device for a PCR analyzer and a PCR analyzer, wherein the PCR analyzer is used to simulate the DNA replication process in vivo in vitro based on the amplification principle of polymerase chain reaction (PCR).

[0036] The structures of the PCR analyzer and the temperature control device in this application will be described below. It can be understood that in other embodiments, the temperature control device of this application is not limited to being used only in a PCR analyzer, and can also be used in any device that needs to clamp a sample and keep the sample warm, which is not limited here.

[0037] The PCR analyzer provided by the embodiment of this application includes an optical detection device (not shown in the figure) and the Figures 1 to 3 temperature control device 10 as shown. The optical detection device is connected to the temperature control device 10 through an optical fiber 30. The temperature control device 10 is used to perform cycles of three stages: high-temperature denaturation, low-temperature annealing, and appropriate-temperature extension on the sample to be tested, so as to achieve rapid amplification of the target DNA fragment; the optical detection device is used to emit excitation light to the sample to be tested and receive the fluorescence emitted by the sample to be tested, so as to monitor the reaction process of PCR in real time.

[0038] The temperature control device 10 provided by the embodiments of the present application can be heated to different constant temperatures respectively, such as 55°C, 72°C, and 95°C, so that the sample to be tested can first undergo high-temperature denaturation in an environment of 95°C. At this temperature, the double-stranded DNA in the sample to be tested will dissociate into two single strands; then the sample to be tested can undergo medium-temperature annealing in an environment of 72°C to enable the primer and the target DNA to bind complementarily; then the sample to be tested can undergo appropriate-temperature extension in an environment of 55°C. At this temperature, the activity of the thermostable DNA polymerase is the highest, which can promote the primer to extend and synthesize a new DNA strand on the target DNA sequence.

[0039] Of course, it can be understood that the constant temperatures maintained by the above-mentioned temperature control device 10 are not limited to 55°C, 72°C, and 95°C, and can be changed according to requirements, and can be set according to requirements without special limitations.

[0040] It can also be understood that the above-mentioned temperature control device 10 can be kept constant at only one temperature (such as 55°C), and can be used in cooperation with other multiple temperature control devices 10 to enable the PCR analyzer to have different and stepwise-changing temperatures, so as to be able to replicate and amplify the sample to be tested in the sample carrier 20 at different temperatures respectively. There are no special limitations here either.

[0041] In the specific structure of the temperature control device 10, as Figure 1 、 Figure 2 and Figure 3 shown, the temperature control device 10 includes a fixed seat 110, a first heat insulation component 120, a temperature control component 130, a heat conducting component 140, and a second heat insulation component 150. Among them, the fixed seat 110 is arranged at the bottommost end, and the temperature control component 130 is connected to the upper side of the fixed seat 110 and is used to generate heat to keep the temperature of the temperature control device 10 constant; the first heat insulation component 120 is arranged between the fixed seat 110 and the temperature control component 130, one side of which is connected to the fixed seat 110, and the opposite side is adhesively connected to the temperature control component 130. The function of setting the first heat insulation component 120 is to prevent heat from being transmitted to the fixed seat 110 and reduce heat energy loss; the heat conducting component 140 is attached to the upper side of the temperature control component 130, which is used to carry the sample carrier 20 and conduct the heat generated by the temperature control component 130 to the sample carrier 20; the second heat insulation component 150 is attached to the upper side of the heat conducting component 140, and its function is to provide heat insulation, ensure the temperature uniformity of the heat conducting component 140 and thus improve the temperature uniformity of the sample carrier 20, and also prevent the sample carrier 20 from being thermally deformed by high temperature and ensure the dimensional stability of the sample carrier 20.

[0042] As described above, since the temperature control device 10 needs to be connected to the optical detection device in order to analyze the sample to be tested during replication and amplification, so as to monitor the reaction process of PCR in real time. Therefore, in the temperature control device 10 provided in the embodiment of the present application, multiple optical fibers 30 are connected to the bottom side of the fixing base 110, so that the temperature control device 10 is connected to the optical detection device through the optical fibers 30. The reason for connecting multiple optical fibers 30 is that in this embodiment, as Figure 3 , Figure 4 , Figure 5 and Figure 6 shown, the sample carrier 20 has a plurality of PCR tubes 21 distributed in an array, each PCR tube 21 has a receiving cavity 22 for receiving the sample to be tested, all the optical fibers 30 correspond to all the PCR tubes 21 one by one, and one end of each optical fiber 30 away from the fixing base 110 is connected to the optical detection device, so that the optical detection device can perform optical detection on the sample to be tested in each PCR tube 21 through the optical fiber 30.

[0043] In terms of the connection manner between the optical fiber 30 and the fixing base 110, a plurality of optical fiber connectors 160 distributed in an array are detachably connected to the bottom side of the fixing base 110, and each optical fiber connector 160 is correspondingly connected to an optical fiber 30. Specifically, the optical fiber connector 160 is in the shape of a hollow cylinder, one end of which is threadedly connected to the fixing base 110 for easy disassembly, and the other end is provided with a fixing hole, and one end of the optical fiber 30 away from the optical detection device is inserted into the fixing hole. In this way, the optical fiber 30 does not need to be fixed by gluing, so that the operator can conveniently install the optical fiber 30 independently, which makes the production and manufacturing convenient, the after-sales maintenance cost low, and also makes the installation and fixation of the optical fiber 30 without looseness and the structure simple and reliable.

[0044] Furthermore, in terms of the structure of the first heat insulation component 120, the first heat insulation component 120 includes a first heat insulation cotton 121 and a plurality of heat insulation balls 122 arranged at equal intervals. The upper side of the first heat insulation cotton 121 is attached to the temperature control element 130, the lower side is spaced from the fixing base 110, and is connected to the fixing base 110 through the above-mentioned plurality of heat insulation balls 122 in a point connection manner. The heat insulation balls 122 are preferably ceramic balls, because the pressure resistance of a single ceramic ball can be greater than 50 Kg, and the high-precision size of the heat insulation balls 122 can ensure the parallelism between the first heat insulation cotton 121 and the fixing base 110. Moreover, since the heat insulation balls 122 are in point contact with both the first heat insulation cotton 121 and the fixing base 110, the heat generated by the temperature control element 130 is not easily transferred to the fixing base 110. More preferably, the first heat insulation cotton 121 is made of an aerogel material. This kind of material has an aerogel pore size of 20 - 50 nm, a porosity as high as more than 95%, and a minimum thermal conductivity of 0.014 W / m·k, which can form a heat barrier layer, making the heat generated by the temperature control element 130 more difficult to transfer to the fixing base 110, thereby further effectively avoiding heat energy loss.

[0045] Preferably, the temperature control member 130 has a plate-like structure, which includes a substrate and a heating element. The heating element is disposed in the substrate according to the heating distribution of the temperature control member 130, so that the temperature control member 130 can generate uniform heat to compensate the temperature around the temperature control member 130, thereby effectively avoiding the edge effect of high temperature in the middle and low temperature around, and making the temperature uniformity of the temperature control device 10 good.

[0046] In terms of the structure of the heat conducting member 140, as Figure 4 shown, a plurality of jacks 141 arranged in an array are formed on one side of the heat conducting member 140 facing the second heat insulation assembly 150, and the number of the jacks 141 corresponds to the number of the accommodating cavities 22 on the sample carrier 20 respectively. The second heat insulation assembly 150 includes a heat insulation protective cover 151 and a second heat insulation cotton 152. The heat insulation protective cover 151 is disposed on one side of the second heat insulation cotton 152 in its own thickness direction. The side of the second heat insulation cotton 152 facing away from the heat insulation protective cover 151 is attached to the heat conducting member 140, and a plurality of through holes (not marked in the figure) arranged in an array are respectively formed in the heat insulation protective cover 151 and the second heat insulation cotton 152. The number of the through holes corresponds to the number of the PCR tubes 21 of the sample carrier 20. In this way, the PCR tubes 21 of the sample carrier 20 pass through the heat insulation protective cover 151 and the second heat insulation cotton 152 and are inserted into the jacks 141 of the heat conducting member 140. In this way, it can be ensured that the test samples in each PCR tube 21 can be heated evenly, and the phenomenon that the test samples in different accommodating cavities 22 are heated unevenly can be avoided.

[0047] In some cases, based on the analysis needs, some of the test samples contain magnetic beads made of ferromagnetic materials. The purpose is to specifically bind the special structure on the surface of the magnetic beads to the nucleic acid molecules of the test samples, so as to perform simple and efficient nucleic acid purification. When performing optical detection on the test samples, in order to avoid the magnetic beads settling and affecting the detection signal, thereby affecting the detection result, in a preferred embodiment, a plurality of magnets arranged in an array are further embedded in the first heat conducting member 140, that is, the magnets are embedded between any two adjacent jacks 141 in the first heat conducting member 140. In this way, when the test samples contain magnetic beads and the sample carrier 20 is placed on the second heat insulation assembly 150, the magnetic beads can be quickly adsorbed by the corresponding magnets to the side wall of the accommodating cavity 22, so that the magnetic beads can be quickly settled, avoiding the magnetic beads from blocking the excitation light or the reflected light, eliminating the influence of the magnetic beads on the detection, and further not affecting the detection signal, thus the detection time can be shortened.

[0048] In addition, a temperature sensor is further provided on the heat conducting member 140 to be used for monitoring the temperature of the heat conducting member 140 in real time after the heat generated by the temperature control member 130 is conducted to the heat conducting member 140; further, an induction element 170 is further provided on the fixing base 110 to detect whether the sample carrier 20 is carried on the temperature control device 10.

[0049] As can be seen, for the temperature control device 10 provided by the embodiment of the present application, on the one hand, by arranging the first heat insulation component 120 between the fixed seat 110 and the temperature control component 130, the heat generated by the temperature control component 130 is not easily transferred to the fixed seat 110, so that heat energy loss can be reduced, ensuring that the temperature control device 10 can quickly reach the required reaction temperature and improving the test efficiency of the PCR reaction; on the other hand, by arranging the second heat insulation component 150 on the upper side of the heat conducting member 140, when the sample carrier 20 is carried on the heat conducting member 140, the second heat insulation component 150 can be located between the heat conducting member 140 and the sample carrier 20, thereby preventing the influence of the ambient temperature on the heat conducting member 140, playing a role of heat preservation and insulation, ensuring the temperature uniformity of the heat conducting member 140 and further ensuring the temperature uniformity of the sample carrier 20, and further ensuring that the temperature control device 10 can quickly reach the required reaction temperature.

[0050] The technical features of the above-described embodiments can be combined arbitrarily. For the sake of brevity of description, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, it should be considered as the scope described in this specification.

[0051] The above-described embodiments only represent several implementation manners of the present application. The description is relatively specific and detailed, but it should not be construed as a limitation on the scope of the patent application. It should be noted that for those of ordinary skill in the art, without departing from the concept of the present application, several modifications and improvements can still be made, and these all belong to the protection scope of the present application. Therefore, the protection scope of the patent of the present application shall be subject to the appended claims.

Claims

1. A temperature control device for a PCR analyzer, characterized in that: The temperature control device comprises: Fixed seat; A temperature control unit connected to the upper side of the fixing seat, the temperature control unit is used to generate heat; A first heat-insulating component is disposed between the fixing seat and the temperature control unit, wherein one side of the first heat-insulating component is connected to the fixing seat, and the other side is closely connected to the temperature control unit; A heat conducting member, attached to the upper side of the temperature control member, the heat conducting member is used to carry the sample carrier and to conduct the heat generated by the temperature control member to the sample carrier; The second thermal insulation component is attached to the upper side of the heat conductive component, and is used for thermally insulating the sample carrier.

2. The temperature control device according to claim 1, characterized in that: The first thermal insulation component includes a first thermal insulation cotton and a plurality of thermal insulation balls connected to the first thermal insulation cotton and arranged at intervals. The first thermal insulation cotton is arranged at intervals from the fixing seat and is connected to the fixing seat through a plurality of thermal insulation ball points.

3. The temperature control device according to claim 2, characterized in that: The material of the first thermal insulation cotton is aerogel material.

4. The temperature control device according to claim 1, characterized in that: The heat conductive part is provided with a plurality of insertion holes distributed in an array, the second heat insulation component includes a heat insulation protective cover and a second heat insulation cotton, the heat insulation protective cover and the second heat insulation cotton are both provided with a plurality of through holes penetrating opposite sides thereof and distributed in an array, the insertion holes correspond to the through holes one by one, and the insertion holes correspond to the through holes one by one with the plurality of PCR tubes of the sample carrier respectively, each of the through holes is used for a corresponding one of the PCR tubes to pass through, and each of the insertion holes is used for a corresponding one of the PCR tubes to be inserted.

5. The temperature control device according to claim 4, characterized in that: A plurality of optical fiber connectors are arranged on the lower side of the fixing seat, all of the optical fiber connectors correspond to all of the jacks one by one, and each of the optical fiber connectors is used to connect to an optical fiber.

6. The temperature control device according to claim 5, characterized in that: The optical fiber connector is detachably connected to the fixing seat.

7. The temperature control device according to claim 4, characterized in that: A plurality of magnets distributed in an array are embedded in the heat conductive member, and any one of the magnets is disposed between two adjacent jacks. The magnet is configured to adsorb the magnetic beads to the tube wall of the PCR tube when the heat conductive member carries the sample carrier and there are magnetic beads in the sample in the sample carrier.

8. The temperature control device according to claim 1, characterized in that: The second thermal insulation component includes a second thermal insulation cotton and a thermal insulation protective cover. The thermal insulation protective cover is arranged on one side of the second thermal insulation cotton in its own thickness direction, and the side of the second thermal insulation cotton away from the thermal insulation protective cover is attached to the heat conductive member.

9. The temperature control device according to claim 1, characterized in that: The temperature control unit includes a substrate and a heating element, and the heating element is arranged in the substrate according to the heating distribution condition of the temperature control unit.

10. A PCR analyzer, characterized in that: It comprises an optical detection device and a temperature control device as described in any one of claims 1 to 9, wherein the optical detection device is connected to a fixing seat of the temperature control device via an optical fiber.

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