Modules, methods, and PCR apparatus for balancing heat transfer differences in the receiving section of sample tubes

Abstract

This invention discloses a module, method, and PCR apparatus for balancing heat transfer differences in sample tube receiving sections. The module includes an array-type receiving section, comprising a base and multiple sample tube receiving units. The base heats the multiple sample tube receiving units via heat transfer with an external heat source. The array-type receiving section is divided into multiple units to be balanced. At least one of these units is equipped with a heat transfer difference balancing section, which is located above the base at the periphery of the at least one unit to be balanced. This invention, by dividing the array-type receiving section and utilizing the heat transfer difference balancing section to alter the heat transfer characteristics, ensures that when the array-type receiving section receives heat from an external heat source, the heat transfer difference balancing section ensures that the power-to-heat-capacity ratio between any two units to be balanced does not exceed 5%. The power-to-heat-capacity ratio is the ratio of heat power to heat capacity within the same unit to be balanced. This invention achieves a high-precision heat transfer difference balancing effect.

Description

Technical Field

[0001] This invention belongs to the field of heat transfer optimization technology, specifically relating to a module, method, and PCR device that can balance the heat transfer differences in the receiving part of a sample tube. Background Technology

[0002] In fields such as biomedicine, heating is a fundamental condition for triggering and maintaining reactions. However, the reaction targets in general biomedicine are often numerous, usually dozens. In such cases, the design of array-type receivers with arrayed arrangements is essential, as this allows a relatively large number of reactions to be carried out simultaneously. Among them, polymerase chain reaction (PCR) is widely used in various scenarios, such as in vitro diagnostic screening for different diseases, screening for congenital malformations in infants and young children, DNA identification and analysis in criminal investigations, and disease prevention and control in the livestock industry.

[0003] In PCR-based assays, the most common setup is to arrange the array-type receiver section in microplate structures with 36, 48, 96, or 192 wells. These are called warm blocks, heat blocks, or sample blocks. Heat from the heat source is transferred to the PCR consumables in the receiver section through these blocks. PCR consumables are usually plastic tubes. This provides the heat required for the PCR reaction to be performed on the sample solution within the consumables. Generally, the size of the heat source is limited by factors such as power and heat uniformity. Therefore, for array-type receiver sections, multiple heat sources are usually required to meet the PCR amplification reaction of a specific number of sample tubes. US Patent 7771933B2 discloses a heating scheme for a 96-hole plate that utilizes six independent heat sources and thermal isolation blocks between them to form six interconnected areas. This scheme focuses on the independence of the heat sources, aiming to achieve a relatively consistent temperature control in each area by minimizing the influence between different heat sources. PCT International Application WO2020190035A1 further divides the module's heat sink into essentially independent heat sink and heat block combinations. This allows for mutual influence between independent heat blocks, while fewer heat sources can be used within each largely independent heat block, thus ensuring a smaller temperature difference between different holes within the same module. US Patent Application 20170266667A1 specifies a heat source... The optimization direction for heating and cooling array-type heating blocks is to ensure that the area of ​​the lower heat transfer surface is larger than the area of ​​the upper sample receiving surface. This ensures that the edge holes of the heating block do not have a large temperature difference with the holes in the central area of ​​the heating block due to their positional disadvantage. To address the issue of poor heat transfer at the edge holes, US Patent 10226770B2 discloses a solution of connecting supplementary heating elements to the edge of the heating block by embedding. Regarding the current exploration of methods for achieving temperature difference balance within the heating block under heat source heating, Japanese Patent JP5975593B2 discloses a solution of arranging temperature sensors within the heating block. This allows for adjustment of the output power of the heat source in different heating areas through temperature feedback in different regions, thereby obtaining a real-time temperature difference adjustment thermal cycle solution.

[0004] The heating methods mentioned above are mostly designed from the perspective of heat source power compensation, and then thermal balance design is carried out for the temperature blocks of the multi-sample receiving unit. However, these designs have problems such as limited control of complex application scenarios. There are few solutions that focus on the characteristics of the temperature block itself and analyze the fundamental factors that cause heat transfer differences in the temperature block itself to eliminate thermal differences. There is an urgent need to develop a solution that can solve the heat transfer differences in the temperature block to ensure that the reactions in multiple reaction tubes have basically consistent temperature characteristics. Summary of the Invention

[0005] To address the aforementioned problems in the prior art, the present invention is achieved through the following technical solution:

[0006] A first aspect of the invention provides a module for balancing heat transfer differences in sample tube receiving sections, comprising an array-type receiving section, the array-type receiving section including a base and a plurality of sample tube receiving units located on the base, the base heating the plurality of sample tube receiving units through heat transfer with an external heat source, the array-type receiving section being divided into N units to be balanced, wherein N is an integer greater than or equal to two, at least one of the N units to be balanced is provided with a heat transfer difference balancing section, the heat transfer difference balancing section being disposed above the base at the peripheral edge of the at least one unit to be balanced, when the array-type receiving section receives heat transfer from the external heat source, the heat transfer difference balancing section ensures that the power-to-heat capacity ratio between any two units to be balanced does not exceed 5%, the power-to-heat capacity ratio being the ratio of heat power to heat capacity within the same unit to be balanced.

[0007] In one embodiment of the present invention, the sample tube receiving unit in the at least one unit to be balanced is spaced apart from the heat transfer difference balancing section.

[0008] In one embodiment of the present invention, the heat transfer difference balancing section is detachably disposed above the base of the peripheral edge of the at least one unit to be balanced.

[0009] In one embodiment of the present invention, both the heat transfer difference balancing part and the array-type receiving part are made of metal.

[0010] In one embodiment of the present invention, the heat transfer difference balancing part is made of the same material as the array-type receiving part.

[0011] In one embodiment of the present invention, the thickness of the heat transfer difference balance section decreases from the center to both sides.

[0012] In one embodiment of the present invention, the array-type receiving unit is further provided with reinforcing ribs, and the plurality of sample tube receiving units are connected to each other through the reinforcing ribs.

[0013] In one embodiment of the present invention, the reinforcing rib is made of the same material as the array-type receiver.

[0014] A second aspect of the invention provides a method for balancing heat transfer differences in a sample tube receiving section, the method being applied to a module for balancing heat transfer differences in a sample tube receiving section, the module comprising an array-type receiving section, the array-type receiving section comprising a base and a plurality of sample tube receiving units located on the base, the method comprising:

[0015] Step 1: Divide the array-type receiver into N units to be balanced, where N is an integer greater than or equal to two;

[0016] Step 2: Configure a heat transfer difference balancing unit for at least one of the N units to be balanced;

[0017] Step 3: Heat the base with an external heat source so that the N units to be balanced can achieve heat transfer difference balance.

[0018] A third aspect of the present invention provides a PCR apparatus capable of balancing heat transfer differences in the receiving section of a sample tube, comprising the module capable of balancing heat transfer differences in the receiving section of the sample tube.

[0019] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0020] 1. This invention, using a method similar to finite element analysis, divides the array-type receiving unit into multiple units to be balanced. A heat transfer difference balancing unit is used to alter the heat transfer characteristics of these units, ensuring that the power-to-heat capacity ratio between any two units does not exceed 5%. This achieves a simpler and more reliable effect than the traditional method of using the negative feedback signal from a temperature sensor as a control signal to change the heating power of the heat source. By employing a segmentation approach combined with a unit balancing method similar to finite element analysis, heat transfer differences are balanced between units, resulting in more consistent overall heat transfer characteristics. Furthermore, using different numbers of units to be balanced enables a higher precision in balancing heat transfer differences.

[0021] 2. Furthermore, by configuring the heat transfer difference balancing section and the array-type receiving section with the same material, this invention makes it easier to configure the heat transfer difference balancing section to meet the requirement that adjacent units to be balanced have a heat capacity difference of no more than 5%, so as to meet the balance of heat transfer performance of different units to be balanced. At the same time, by adjusting the configuration of the heat transfer difference balancing section in the unit to be balanced, the maximum temperature difference within the unit to be balanced is not more than 4°C at a specific heating and cooling rate during PCR heating and cooling operations, so as to meet the requirements of transient performance of the module in special application scenarios.

[0022] 3. The method for balancing the heat transfer difference of the sample tube receiving section provided by the present invention divides the array-type receiving section into N units to be balanced according to the requirements, and configures a balancing part in some of the units to be balanced, thereby realizing the heat transfer difference balance of the entire module that can balance the heat transfer difference of the sample tube receiving section. This method is simple, efficient and does not require complex control, thus reducing the cost of balancing the heat transfer difference of the sample tube receiving section.

[0023] The present invention will be further described in detail below with reference to the accompanying drawings and embodiments. Attached Figure Description

[0024] Figure 1 This is a schematic diagram of the structure of a module that can balance the heat transfer differences of the receiving part of the sample tube, provided in an embodiment of the present invention;

[0025] Figure 2 This is a top view of a module that can balance the heat transfer differences in the receiving part of a sample tube, according to an embodiment of the present invention.

[0026] Figure 3 This is a schematic diagram of another module provided in an embodiment of the present invention, which is divided into multiple units to be balanced and can balance the heat transfer differences of the receiving part of the sample tube.

[0027] Figure 4 This is a schematic diagram of the structure of a PCR device that can balance the heat transfer differences of the sample tube receiving section according to an embodiment of the present invention;

[0028] Figure 5 yes Figure 4 Exploded view of the PCR device;

[0029] Figure 6 yes Figure 4 A schematic diagram of the module in a PCR device that balances the heat transfer differences in the sample tube receiving section;

[0030] Figure 7 yes Figure 6 A schematic diagram showing the deployment of temperature sensors in different sample tube receiving units within a module that balances the heat transfer differences in the sample tube receiving section.

[0031] Figure 8 a) in the text is Figure 4 When the provided PCR device does not have a heat transfer differential equilibrium section, the statistical graph shows the range of heating rates of different sample tube receiving sections when the heat source heats the receiving section at a preset temperature. Figure 8 b) is Figure 4 A statistical graph showing the range of heating rates of different sample tube receiving sections when the heat source in the provided PCR device is heated to a preset temperature.

[0032] Figure 9 (a) in the middle is Figure 4 A statistical diagram illustrating the range of cooling rates of different sample tube receiving sections when the provided PCR device lacks a heat transfer differential equilibrium section, based on the preset temperature cooling method. Figure 9 (b) in the middle is Figure 4 A statistical diagram showing the extreme difference in cooling rates of different sample tube receiving sections when the provided PCR device is cooled to a preset temperature.

[0033] Figure 10 Is with Figure 4 A schematic diagram of the heat transfer response of the module in the provided PCR device that can balance the heat transfer difference of the sample tube receiving section when other conditions are the same but no heat transfer difference balancing section is set up.

[0034] Figure 11 yes Figure 4A schematic diagram of the heat transfer response of the module in the provided PCR device that balances the heat transfer differences in the sample tube receiving section.

[0035] Figure 12(a) is Figure 4 Figure 12(b) shows the temperature response in different sample tube receiving units during the heating process when the provided PCR apparatus does not have a heat transfer differential equilibrium section. Figure 4 A schematic diagram showing the temperature response within different sample tube receiving units during the heating process of the provided PCR device;

[0036] Figure 13(a) is Figure 4 The transient performance of the provided PCR device at a heating rate within a preset range is shown in Figure 13(b). Figure 4 Transient performance of the provided PCR device at a cooling rate within a preset rate range;

[0037] 1-Array-type receiving section; 10-Base; 11-Sample tube receiving unit; 12-Reinforcing rib; 2-Heat transfer differential balancing section; 3-Geometric center line; 4-First heat transfer enhancement unit; 5-Heating source; 6-Second heat transfer enhancement unit; 7-Radiator; 71-Heat transfer section; source-Heat source; source 11 - First heat source; source 21 - Second heat source; L1-First transverse dividing line, L2-Second transverse dividing line, L3-Third transverse dividing line; V1-First longitudinal dividing line; V2-Second longitudinal dividing line; V3-Third longitudinal dividing line; 100-First unit to be balanced; 200-Second unit to be balanced; 300-Third unit to be balanced; 400-Fourth unit to be balanced; 500-Fifth unit to be balanced; 600-Sixth unit to be balanced; 700-Seventh unit to be balanced; 800-Eighth unit to be balanced; 900-Ninth unit to be balanced; 1000-Tenth unit to be balanced; 1100-Eleventh unit to be balanced; 1200-Twelfth unit to be balanced; 1300-Thirteenth unit to be balanced; 1400-Fourteenth unit to be balanced; 1500-Fifteenth unit to be balanced; 1600-Sixteenth unit to be balanced; M1-First module; M2-Second module. Detailed Implementation

[0038] To further illustrate the technical means and effects adopted by the present invention to achieve the intended purpose, the following detailed description of the solution according to the present invention is provided in conjunction with the accompanying drawings and specific embodiments.

[0039] The foregoing and other technical contents, features, and effects of the present invention will be clearly presented in the following detailed description of specific embodiments in conjunction with the accompanying drawings. Through the description of the specific embodiments, a more in-depth and concrete understanding can be gained of the technical means and effects adopted by the present invention to achieve its intended purpose. However, the accompanying drawings are for reference and illustration only and are not intended to limit the technical solutions of the present invention.

[0040] It should be noted that, in this document, relational terms such as "first" and "second" are used merely to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising," "including," or any other variations are intended to cover non-exclusive inclusion, such that an article or apparatus comprising a list of elements includes not only those elements but also other elements not expressly listed. Without further limitations, an element defined by the phrase "comprising one..." does not exclude the presence of other identical elements in the article or apparatus that includes said element.

[0041] Please see Figure 1 and Figure 2 , Figure 1 This is a schematic diagram of the structure of a module that can balance the heat transfer differences in the receiving part of a sample tube, according to an embodiment of the present invention. Figure 2 This is a top view of a module for balancing heat transfer differences in sample tube receiving sections according to an embodiment of the present invention. The module includes an array-type receiving section 1, which comprises a base 10 and multiple sample tube receiving units 11 located on the base 10. Typically, the array-type receiving section 1 is made of a uniform material, meaning the base 10 and the multiple sample tube receiving units 11 on the base 10 are made of the same material. The base 10 heats the multiple sample tube receiving units 11 through heat transfer with an external heat source. The array-type receiving section 1 is divided into N units to be balanced, where N is an integer greater than or equal to two. In this embodiment, the array-type receiving unit 1 includes 16 sample tube receiving units 11 arranged in an array. The horizontal geometric center line 3 divides the array-type receiving unit 1 into two units to be balanced, namely the first unit to be balanced 100 and the second unit to be balanced 200. The division here is a virtual conceptual processing, using segmentation analysis thinking, and does not divide the array-type receiving unit 1 into multiple physically divisible units. In practical applications, the array-type receiving unit 1 can also be divided into other numbers of units to be balanced.

[0042] Furthermore, the array-type receiving part 1 is also provided with reinforcing ribs 12, and multiple sample tube receiving units 11 are connected by reinforcing ribs 12. Preferably, the reinforcing ribs 12 are made of the same material as the array-type receiving part 1, so as to enhance the heat transfer efficiency of the sample tubes at different positions, and at the same time, they can also play a mechanical reinforcing support role for the sample tubes and the substrate.

[0043] In this embodiment, since some sample tube receiving units 11 in the first unit to be balanced 100 are located at the edge, in order to ensure that the heat transfer of the sample tube receiving units 11 located at the edge is not affected, in actual applications, the heat source also covers the edge position beyond the area where the sample tube receiving units 11 are set. The second unit to be balanced 200 is located in the area adjacent to another array-type receiving part 1. The sample tube receiving units 11 arranged in the second unit to be balanced 200 are closer to the edge of the array-type receiving part 1. Therefore, the heat transfer of the heat source in the first unit to be balanced 100 and the second unit to be balanced 200 is very different.

[0044] Existing technologies are generally designed from the perspective of the heat source. For example, auxiliary heat sources are set up at the base 10 locations to supplement heat, and the heat sources are configured as more independent units. Different heating power is controlled and output in conjunction with the negative feedback of the temperature sensor. These solutions have a balancing effect on the temperature differences at different locations within the temperature block. However, the control is relatively complex or the compensation scheme can only be applied to specific locations. Furthermore, the cost-effectiveness of improving thermal uniformity from the heat source end is low. By analyzing the nature of the heat transfer differences generated in the temperature block, improvements from the heat transfer end are highly cost-effective. Therefore, this invention optimizes the design from the heat transfer end. Heat transfer is a common natural phenomenon. The development of modern science has revealed the essential characteristics of heat transfer, leading to the development of a systematic discipline called heat transfer science. This also explains the complex nature of the heat transfer process itself. Generally speaking, any heat transfer process can be classified into a computational model that includes at least one of thermal radiation, thermal convection, and thermal conduction. Such computational models can cover most scenarios and can also serve as the theoretical basis for heat transfer optimization. In biological experiments or medical testing, many processes involve heat transfer. In these fields, efficient parallel processing of multiple objects is generally used to ensure that each analyzed or tested object receives minimal heat from the heat source, thus ensuring basically consistent reaction conditions.

[0045] This invention utilizes a method similar to the finite element method, using the power-to-heat-capacity ratio obtained from the heat source within each unit to be balanced as the balancing standard. The power-to-heat-capacity ratio is the ratio of heat power to heat capacity within the same unit. By setting a heat transfer differential balancing section 2 for at least one of the N units to be balanced, specifically, the heat transfer differential balancing section 2 is configured for the N units to be balanced according to the requirement that the power-to-heat-capacity ratio between any two adjacent units to be balanced does not exceed 5%. This ensures that when the array-type receiving unit 1 receives heat transfer from the external heat source, the heat transfer differential balancing section 2 ensures that the power-to-heat-capacity ratio between any two units to be balanced does not exceed 5%, thereby achieving a balance of heat transfer characteristics within the N units divided by the dividing line. It also ensures that the sample tube receiving units 11 within each unit to be balanced have a basically consistent reaction temperature.

[0046] Please see Figure 3 , Figure 3 This is a schematic diagram of another module for balancing heat transfer differences in the receiving section of a sample tube, provided by an embodiment of the present invention, which is divided into multiple units to be balanced. To accurately balance the heat transfer differences in the array-type receiving section 1, this embodiment uses more dividing lines to divide the module into more units to be balanced. The array-type receiving section 1 is divided into sixteen units to be balanced by the first horizontal dividing line L1, the second horizontal dividing line L2, the third horizontal dividing line L3, and the first vertical dividing line V1, the second vertical dividing line V2, and the third vertical dividing line V3. These are: the first unit to be balanced 1... 00, the second unit to be balanced 200, the third unit to be balanced 300, the fourth unit to be balanced 400, the fifth unit to be balanced 500, the sixth unit to be balanced 600, the seventh unit to be balanced 700, the eighth unit to be balanced 800, the ninth unit to be balanced 900, the tenth unit to be balanced 1000, the eleventh unit to be balanced 1100, the twelfth unit to be balanced 1200, the thirteenth unit to be balanced 1300, the fourteenth unit to be balanced 1400, the fifteenth unit to be balanced 1500, and the sixteenth unit to be balanced 1600, according to the aforementioned Figure 2The standard for analyzing the units to be balanced is to provide a heat transfer differential balancing section 2 for at least one of the multiple units to be balanced. This heat transfer differential balancing section 2 ensures that the power-to-heat ratio obtained by any two units from the heat source does not exceed 5%. When the materials of the heat transfer differential balancing section 2 and the array-type receiving section 1 are the same, the heat transfer differential balancing section 2 ensures that any two units to be balanced have a heat capacity difference of no more than 5%. In terms of dynamic performance, when the heat transfer differential balancing section 2 causes the array-type receiving section 1 to heat up / cool down at a rate within a preset range, the difference in heating / cooling rates between the module with the heat transfer differential balancing section 2 and the module without the heat transfer differential balancing section 2 is reduced by at least 40%. The figure shows the heat transfer differential balancing section 2 formed by configuring multiple units to be balanced through analysis. In other embodiments, the dividing lines for dividing the modules may not adopt the cross-sectional scheme shown in the figure. The array-type receiving section 1 can be divided into other numbers of units to be balanced according to actual needs, and the heat transfer differential balancing section 2 can be configured accordingly. For example, a sector-like division scheme can also be used; this invention does not limit this.

[0047] This embodiment explores and analyzes the essence of heat transfer differences. Due to heating requirements, sample tube array arrangement, and the influence of the heat source's own characteristics, the heat transfer characteristics of each unit to be balanced differ. Using a finite element analysis-like approach, the array-type receiving unit 1 is divided into multiple units to be balanced. The heat transfer difference balancing unit 2 is used to change the heat transfer characteristics between the units to be balanced, ensuring that the power-to-heat ratio of any two units to be balanced does not exceed 5%. This achieves a simpler and more reliable effect than the traditional method of using the negative feedback signal of a temperature sensor as a control signal to change the heating power of the heat source. By using a segmentation approach combined with a unit balancing method similar to finite element analysis, the heat transfer differences between units are balanced, resulting in more consistent overall heat transfer characteristics. Furthermore, using different numbers of units to be balanced can achieve a higher precision in balancing the heat transfer differences.

[0048] Preferably, the heat transfer differential balancing part 2 is disposed above the base 10 at the peripheral edge of at least one unit to be balanced. Specifically, the heat transfer differential balancing part 2 is fixed above the base 10 at the peripheral edge of the at least one unit to be balanced by fusion or welding, or the heat transfer differential balancing part 2 is detachably disposed above the base 10 at the peripheral edge of the at least one unit to be balanced, for example, by threaded connection of the base 10 and the heat transfer differential balancing part 2, so as to facilitate reuse or upgrade. Preferably, the sample tube receiving unit 11 in the at least one unit to be balanced is spaced apart from the heat transfer differential balancing part 2 to avoid direct contact interfering with the temperature distribution within the adjacent sample tube receiving unit 11.

[0049] Preferably, the thickness of the heat transfer difference balancing section 2 decreases from the center to both sides to reduce the impact on the heat distribution characteristics of the sample tube receiving units 11 at the corners. Preferably, the thickness of the heat transfer difference balancing section 2 is less than or equal to the height of the plurality of sample tube receiving units 11 to avoid interfering with the temperature distribution within adjacent sample tube receiving units 11.

[0050] Furthermore, since non-metallic materials have a large heat capacity, using them as the heat transfer differential balancing part 2 would result in a particularly large heat transfer inertia for the entire system, which is very disadvantageous for modules that require temperature changes during the reaction process. Therefore, both the heat transfer differential balancing part 2 and the array-type receiving part 1 are made of metal to improve the efficiency of temperature changes during the reaction process. The heat transfer differential balancing part 2 and the array-type receiving part 1 can be made of different materials; for example, the array-type receiving part 1 can be made of Al, while the heat transfer differential balancing part 2 can be made of Cu. Preferably, the heat transfer differential balancing part 2 and the array-type receiving part 1 are made of the same material, for example, both can be made of Cu, Al, Fe, etc. When the heat transfer difference balancing part 2 and the array-type receiving part 1 are made of the same material, it is easier to configure the heat transfer difference balancing part 2 to meet the requirement that the heat capacity difference between adjacent units to be balanced does not exceed 5%, so as to meet the balance of heat transfer performance of different units to be balanced, making the design simple and reliable. At the same time, by adjusting the configuration of the heat transfer difference balancing part 2 in the unit to be balanced, the maximum temperature difference within the unit to be balanced at a specific heating / cooling rate during PCR heating / cooling operations does not exceed 4℃, so as to meet the requirements of the transient performance of the module in special application scenarios.

[0051] Please see Figure 4 and Figure 5 , Figure 4 This is a schematic diagram of the structure of a PCR device that can balance the heat transfer differences in the receiving part of the sample tube according to an embodiment of the present invention. Figure 5 yes Figure 4 The exploded view of the PCR device shows that the PCR device includes, from top to bottom, the aforementioned module for balancing the heat transfer differences of the sample tube receiving section, the first heat transfer enhancement unit 4, the heating source 5, the second heat transfer enhancement unit 6, and the heat sink 7.

[0052] The PCR device includes at least one module capable of balancing heat transfer differences in the sample tube receiving section. In this embodiment, such as... Figure 6 As shown, the PCR device includes a temperature block formed by splicing two modules that can balance the heat transfer differences in the sample tube receiving sections. These two modules are the first module M1 and the second module M2, respectively. Each module is further configured as described above. Figure 2The method is divided into two units to be balanced, i.e., N=2. The array-type receiving part 1 of each unit to be balanced can receive sixteen sample tubes. The heat transfer difference balancing part 2 of each module is located above the base 10 of at least one unit to be balanced in the module, i.e. outside the range of the array-type receiving part 1 distributed above the base 10.

[0053] Please continue reading Figure 5 The first heat transfer enhancement unit 4 is disposed below the at least one module that balances the heat transfer difference of the sample tube receiving section, and is used to heat the at least one module that balances the heat transfer difference of the sample tube receiving section. The heating source 5 is disposed below the first heat transfer enhancement unit 4 to provide a heat source. The second heat transfer enhancement unit 6 is disposed below the heating source 5. The heat sink 7 is disposed below the heating source 5. In order to improve the heat dissipation efficiency, a heat transfer section 71 is also provided on the upper surface of the heat sink 7. The heat transfer section 71 has a higher processing quality than other components, for example, a higher processing precision requirement, in order to improve the heat dissipation efficiency.

[0054] Preferably, the surface area of ​​the first heat transfer enhancement unit 4, the heat transfer coverage area of ​​the heating source 5, the surface area of ​​the second heat transfer enhancement unit 6, and the surface area of ​​the heat transfer part 71 all cover the surface area of ​​the at least one module that can balance the heat transfer difference of the sample tube receiving part, making the whole design more compact and reducing the heat transfer difference between each module.

[0055] In this embodiment, the heating source 5 is configured as two Peltier sub-heat sources, namely the first sub-heat source. 11 Second heat source 21 These two sub-heat sources are respectively set below the first heat transfer enhancement unit 4 under the two modules that can balance the heat transfer difference of the sample tube receiving part, which can further reduce the heat transfer difference between each module.

[0056] By combining this PCR device with a heat dissipation duct and cooling fan, a PCR thermal cycling module can be formed. By configuring one or more PCR thermal cycling modules, a high-throughput PCR thermal cycling device can be formed, which can achieve efficient and rapid PCR amplification reactions.

[0057] Please see Figure 7 , Figure 7 yes Figure 6 A schematic diagram illustrating the deployment of temperature sensors within different sample tube receiving units in a module that balances heat transfer differences in the sample tube receiving section. Specifically, Figure 7 The leftmost block 11 and block 21 They are used to represent the first module M1 and the second module M2, respectively. Figure 7The list formed by combining the numbers 1-4 in the first row and AD in the first column of A) is used to represent each sample tube receiving unit 11 in the first module M1 from left to right and from top to bottom. In the same way, Figure 7 The list formed by combining the numbers 1-4 in the first row and EH in the first column of module A) is used to represent each sample tube receiving unit 11 in the second module M2 from left to right and from top to bottom. It should be noted that... Figure 7 The numbers 1-12 in the table in section A) are used to characterize the locations of the twelve temperature sensors. For example, 6 indicates that the sixth temperature sensor is placed in the sample tube receiving unit 11, located in the 3rd row and 3rd column of the first module M1. Similar to... Figure 7 A), Figure 7 B) and Figure 7 C) represents the positions of the twelve temperature sensors after they have moved in the first module M1 and the second module M2. In this embodiment, twelve temperature sensors are used to collect data and perform position changes to obtain the temperature characteristics and heat transfer characteristics inside the sample tube at different positions more accurately.

[0058] Please see Figure 8 and Figure 9 , Figure 8 a) in the text is Figure 4 When the provided PCR device does not have a heat transfer differential equilibrium section, the statistical graph shows the range of heating rates of different sample tube receiving sections when the heat source heats the receiving section at a preset temperature. Figure 8 b) is Figure 4 A statistical chart showing the range of heating rates of different sample tube receiving sections when the heat source in the provided PCR device is heated to a preset temperature. Figure 9 (a) in the middle is Figure 4 A statistical diagram illustrating the range of cooling rates of different sample tube receiving sections when the provided PCR device lacks a heat transfer differential equilibrium section, based on the preset temperature cooling method. Figure 9 (b) in the middle is Figure 4 A statistical diagram illustrating the wide variation in cooling rates of different sample tube receiving sections when the provided PCR device is cooled to a preset temperature. Specifically, Figure 8 and Figure 9 The function graphs above are all based on Figure 4 This is a schematic diagram of the function plotting of temperature data during the heating and cooling processes of the provided PCR device. The horizontal axis represents time, the vertical axis represents temperature, and the node T... A The temperature value is 93℃, node T B The temperature value is 62℃. The heating rate range refers to the difference between the maximum and minimum heating rates within different sample tube receiving units 11. The cooling rate range refers to the difference between the maximum and minimum cooling rates within different sample tube receiving units 11. Furthermore, the meanings of 1-4 and AH are... Figure 7The meanings are the same, used to characterize Figure 4 The positions of different sample tube receiving units 11 in the provided PCR apparatus are represented by the data in the table (1-4 and AH), which indicates the temperature rate data in the represented sample tube receiving unit 11. 11 and block 21 They are used to represent the first module M1 and the second module M2, respectively. Figure 8 a) Without the heat transfer differential balancing unit 2, the temperature rise rate difference of the first module M1 is 0.96℃ / s, and the temperature rise rate difference of the second module M2 is 1.05℃ / s. In contrast, under the same conditions, with the heat transfer differential balancing unit 2... Figure 8 In (b), the temperature rise rate difference in the first module M1 is 0.56℃ / s, and the temperature rise rate difference in the second module M2 is 0.53℃ / s. It can be seen that, under the same conditions, the module with the heat transfer differential balance section 2 has a temperature rise rate difference that is approximately 50% lower than the module without the heat transfer differential balance section 2. However, during the cooling process, the module without the heat transfer differential balance section 2... Figure 9 In (a), the temperature drop rate difference in the first module M1 is 1.16℃ / s, and the temperature drop rate difference in the second module M2 is 1.35℃ / s. In contrast, a heat transfer differential balancing section 2 is provided. Figure 9 In (b), the temperature drop rate range in the first module M1 is 0.63℃ / s, and the temperature drop rate range in the second module M2 is 0.67℃ / s. It can be seen that the module with the heat transfer difference balancing section 2 has a temperature drop rate range that is at least 40% lower than that of the module without the heat transfer difference balancing section 2. In addition, by configuring the heat transfer difference balancing section 2, the effect of balancing the transient heat transfer rate difference can be taken into account. Since a rate difference reduction of less than 40% may lead to an excessively significant cumulative effect of the difference between different sample tube receiving units 11 in the sample tube receiving section 1, the design of the heat transfer difference balancing section 2 must also meet this characteristic. In the PCR device provided in the embodiment of the present invention, by designing at least one module that can balance the heat transfer difference of the sample tube receiving section, the temperature rise rate decreases by about 4%-5% before and after, and the temperature drop rate decreases by about 7%-8% before and after, and there is no rate change that causes significant difference.

[0059] Please see Figure 10 and Figure 11 , Figure 10 Is with Figure 4 A schematic diagram of the heat transfer response of the module in the provided PCR device that balances the heat transfer differences in the sample tube receiving section, under the same conditions but without the heat transfer difference balancing section. Figure 11 yes Figure 4 A schematic diagram of the heat transfer response of the module in the provided PCR apparatus that balances the heat transfer differences in the sample tube receiving section. The colored blocks in the diagram are... Figure 7The sample tube receiving units represented in the diagram correspond one-to-one. The colors in the color blocks represent the temperature of the corresponding sample tube receiving unit 11. Different colors are used to distinguish different temperature levels. Specifically, they are arranged from low to high temperature as blue, light blue, yellow, and orange. Within the same color, the darker the color, the higher the temperature. Through comparison... Figure 10 and Figure 11 As can be seen from the sensing temperature of the same sample tube receiving unit 11, for the same target temperature, the temperature of each sample tube receiving unit 11 with the heat transfer difference balancing part 2 is more uniform. The temperature range of the sample tube receiving unit 11 without the heat transfer difference balancing part 2 is about 4.32℃, while the temperature range with the heat transfer difference balancing part 2 is about 1.59℃. From the simulation results, the embodiment of the present invention, by dividing the array-type receiving unit 1 into multiple units to be balanced, and setting the heat transfer difference balancing part 2 in at least one of the multiple units to be balanced, can greatly optimize the heat transfer characteristics of the array-type receiving unit 1 from the heat transfer end, making the temperature characteristics of each sample tube receiving unit 11 of the entire array-type receiving unit 1 more uniform.

[0060] Please refer to Figures 12(a) and 12(b), where Figure 12(a) is... Figure 4 Figure 12(b) shows the temperature response in different sample tube receiving units during the heating process when the provided PCR apparatus does not have a heat transfer differential equilibrium section. Figure 4 The provided schematic diagram of temperature response in different sample tube receiving units during the heating process of the PCR device is shown in Figures 12(a) and 12(b). The different colored curves represent the experimental detection values ​​of the actual temperature following characteristics of different sample tube receiving units 11 in the array-type receiving section 1. It can be seen that after adding the heat transfer difference balancing section 2 to the module that can balance the heat transfer difference in the sample tube receiving section in the PCR device, the difference in heating rate between different sample tube receiving units 11 is significantly reduced, which improves the temperature consistency of the array-type receiving section 1 and avoids the problem of excessive temperature rise difference in different sample tube receiving units 11 due to poor consistency when the array-type receiving section 1 needs to dynamically change the reaction temperature of the sample tube receiving units 11.

[0061] Please refer to Figures 13(a) and 13(b). Figure 13(a) is... Figure 4 The transient performance of the provided PCR device at a heating rate within a preset range is shown in Figure 13(b). Figure 4The transient performance of the provided PCR device at a cooling rate within a preset range is shown in Figures 13(a) and 13(b). Specifically, in Figures 13(a) and 13(b), the horizontal axis represents time (in seconds), the left vertical axis represents temperature (in °C), and the right vertical axis represents the real-time temperature range (in °C) and the instantaneous heating rate (in °C / s). In addition, in Figure 13(a), the dense dashed line represents the preset heating rate, the sparse dashed line represents the real-time temperature range, and the solid line represents the heating characteristic curves within the receiving unit 11 of different sample tubes. In Figure 13(b), the dense dashed line represents the preset cooling rate, the sparse dashed line represents the real-time temperature range, and the solid line represents the cooling characteristic curves within the receiving unit 11 of different sample tubes. From the results in Figures 13(a) and 13(b), when the time is 2-10s, when the PCR device is equipped with the heat transfer differential balance section 2, although the heating / cooling rate is somewhat reduced, the heating rate is in the range of 3.5-6.5℃ / s and the cooling rate is in the range of 3-5.5℃ / s. (Generally, manufacturers use a higher heating / cooling rate, such as in the range of 5.5-8℃ / s, to promote its rapid characteristics.) The temperature rise curves of samples in different sample tube receiving units are more convergent and the value difference is very small, as shown by the solid lines of each color in the figure. That is, the consistency of the heating curve is improved. The heat transfer differential balance section 2 also needs to be adjusted according to the maximum range of 4℃ in the heating / cooling process of a single module. Otherwise, it will lead to a large thermal difference between different sample tube receiving units 11. The heating / cooling rate of the heat source output can fluctuate within a preset range, and can be non-constant or decreasing. The heating / cooling rate is configured to not exceed 6.5℃ / s. For example, during the process of heating from the initial temperature to the target temperature, the heating rate can be adjusted within the range of 1-6℃ / s. The cooling process is similar. This variation in the heating / cooling rate of the heat source can better adjust the consistency of the temperature following characteristic curves within each receiving unit. A relatively constant heating / cooling rate would lead to excessive differences in the temperature following characteristics between the sample tube receiving units 11. From the instantaneous rate curve, it is impossible to maintain the heating rate at a high level indefinitely; the rate will gradually decrease after the maximum instantaneous point. Furthermore, it can be seen that the sample tube receiving unit 1 equipped with the heat transfer difference balancing unit 2 can use a larger heating / cooling rate, while existing equipment requires a sudden and significant reduction in the heating / cooling rate to compensate for the problem of excessively large instantaneous temperature response differences between the sample tube receiving units 11 caused by excessively fast heating / cooling rates.

[0062] Furthermore, the present invention also provides a method for balancing heat transfer differences in the sample tube receiving section. This method is applied to the aforementioned module for balancing heat transfer differences in the sample tube receiving section. The module includes an array-type receiving section 1, which includes a base 10 and a plurality of sample tube receiving units 11 located on the base 10. The method includes:

[0063] Step 1: Divide the array-type receiver 1 into N units to be balanced, where N is an integer greater than or equal to two;

[0064] Optionally, the array-type receiving unit 1 is further provided with reinforcing ribs 12, and multiple sample tube receiving units 11 are connected by reinforcing ribs 12. Preferably, the reinforcing ribs 12 are made of the same material as the array-type receiving unit 1.

[0065] Step 2: Configure a heat transfer difference balancing unit 2 for at least one of the N units to be balanced;

[0066] In this embodiment, based on the preset requirement that the heat capacity difference between any two units to be balanced does not exceed 5%, the array-type receiving unit 1 is divided into two units to be balanced, i.e., N=2. A heat transfer difference balancing part 2 is configured for one of these units. This heat transfer difference balancing part 2 is disposed above the base 10 at the peripheral edge of at least one unit to be balanced. Specifically, the heat transfer difference balancing part 2 is fixed above the base 10 at the peripheral edge of the at least one unit to be balanced, for example, by fusion or welding. Alternatively, the heat transfer difference balancing part 2 can be detachably disposed above the base 10 at the peripheral edge of the at least one unit to be balanced, for example, by threaded connection, for reuse or upgrade. In this embodiment, the heat transfer difference balancing part 2 is made by thickening the base 10 at the peripheral edge of the first unit to be balanced 10. By integrally fabricating the heat transfer difference balancing part 2 on the base 10, the fabrication process of the heat transfer difference balancing part 2 is simplified, and the process efficiency is improved. In other embodiments, the array-type receiving unit 1 can be divided into other numbers of units to be balanced as needed, and the heat transfer difference balancing part 2 can be configured accordingly.

[0067] Preferably, at least one sample tube receiving unit 11 in the unit to be balanced is spaced apart from the heat transfer difference balancing part 2 to avoid direct contact and interference with the temperature distribution within the adjacent sample tube receiving unit 11. In this embodiment, the heat transfer difference balancing part 2 is made by thickening the base 10 at the peripheral edge of the first unit to be balanced 100. By integrally preparing the heat transfer difference balancing part 2 on the base 10, the preparation process of the heat transfer difference balancing part 2 is simplified and the process efficiency is improved.

[0068] Preferably, the thickness of the heat transfer difference balancing section 2 decreases from the center to both sides to reduce the impact on the heat distribution characteristics of the sample tube receiving unit 11 at the corner positions.

[0069] Preferably, both the heat transfer difference balancing section 2 and the array-type receiving section 1 are made of metal to improve the efficiency of temperature change during the reaction process.

[0070] Preferably, the heat transfer difference balancing part 2 is made of the same material as the array-type receiving part 1, which makes it easier to configure the heat transfer difference balancing part 2 so that adjacent units to be balanced meet the requirement of a heat capacity difference of no more than 5%.

[0071] Step 3: Heat the base 10 with an external heat source so that the N units to be balanced can achieve heat transfer difference balance.

[0072] Specifically, the base 10 is heated by an external heat source so that the power-to-heat ratio between any two units to be balanced does not exceed 5%.

[0073] The method provided in this embodiment divides the array-type receiving unit 1 into N units to be balanced according to the requirements, and configures a heat transfer difference balancing unit for some of the units to be balanced, thereby realizing the heat transfer difference balancing of the entire module. This method is simple, efficient and does not require complex control, reducing the cost of balancing heat transfer differences.

[0074] The above description, in conjunction with specific preferred embodiments, provides a further detailed explanation of the present invention. It should not be construed that the specific implementation of the present invention is limited to these descriptions. For those skilled in the art, various simple deductions or substitutions can be made without departing from the concept of the present invention, and all such modifications and substitutions should be considered within the scope of protection of the present invention.

Claims

1. A module capable of balancing heat transfer differences in the receiving section of a sample tube, characterized in that, The array-type receiving unit (1) includes a base (10) and multiple sample tube receiving units (11) located on the base (10). The base (10) heats the multiple sample tube receiving units (11) through heat transfer with an external heat source. The array-type receiving unit (1) is divided into N units to be balanced, where N is an integer greater than or equal to two. At least one of the N units to be balanced is provided with a heat transfer difference balancing part (2). The heat transfer difference balancing part (2) is located above the base (10) at the peripheral edge of the at least one unit to be balanced. When the array-type receiving unit... (1) When receiving heat transfer from the external heat source, the heat transfer differential balance part (2) ensures that the power-to-heat capacity ratio between any two units to be balanced in the N units to be balanced does not exceed 5%, and the power-to-heat capacity ratio is the ratio of heat power to heat capacity in the same unit to be balanced; the sample tube receiving unit (11) in at least one unit to be balanced is spaced apart from the heat transfer differential balance part (2); the thickness of the heat transfer differential balance part (2) decreases from the center to both sides; the thickness of the heat transfer differential balance part (2) is less than or equal to the height of the multiple sample tube receiving units (11); the heat transfer differential balance part (2) is made of metal.

2. The module for balancing heat transfer differences in the receiving section of the sample tube according to claim 1, characterized in that, The heat transfer difference balancing part (2) is detachably disposed above the base (10) at the peripheral edge of the at least one unit to be balanced.

3. The module for balancing heat transfer differences in the receiving section of the sample tube according to claim 1, characterized in that, The array-type receiver (1) is made of metal.

4. The module for balancing heat transfer differences in the receiving section of the sample tube according to claim 3, characterized in that, The heat transfer differential balancing part (2) is made of the same material as the array-type receiving part (1).

5. The module for balancing heat transfer differences in the receiving section of the sample tube according to claim 1, characterized in that, The array-type receiving unit (1) is also provided with reinforcing ribs (12), and the plurality of sample tube receiving units (11) are connected to each other through the reinforcing ribs (12).

6. The module for balancing heat transfer differences in the receiving section of the sample tube according to claim 5, characterized in that, The reinforcing rib (12) is made of the same material as the array-type receiver (1).

7. A method for balancing heat transfer differences in the receiving section of a sample tube, characterized in that, The method is applied to the module for balancing heat transfer differences in the sample tube receiving section as described in any one of claims 1-6. The module for balancing heat transfer differences in the sample tube receiving section includes an array-type receiving section (1), which includes a base (10) and a plurality of sample tube receiving units (11) located on the base (10). The method includes: Step 1: Divide the array-type receiving unit (1) into N units to be balanced, where N is an integer greater than or equal to two; Step 2: Configure a heat transfer difference balancing unit (2) for at least one of the N units to be balanced; Step 3: Heat the base (10) with an external heat source so that the N units to be balanced can achieve heat transfer difference balance.

8. A PCR device capable of balancing heat transfer differences in the receiving section of a sample tube, characterized in that, The module comprising any one of claims 1-6 is capable of balancing the heat transfer differences in the receiving section of the sample tube.

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