Method for improving temperature uniformity of PCR pore plate and PCR pore plate

Abstract

The invention discloses a method for improving temperature uniformity of a PCR (polymerase chain reaction) pore plate and the PCR pore plate, and relates to the field of PCR pore plates, the method comprises the following steps: determining the relationship between unit heat density and the thickness of an edge material of the pore plate through a calculation equation of unit heat and unit heat density, and analyzing the influence of the thickness of the edge material of the pore plate on a second type of boundary conditions based on the relationship; designing and setting the thickness of the pore plate edge material according to the correlation between the unit thermal density and the thickness of the pore plate edge material and the analysis result of the influence of the pore plate edge material on the second type of boundary conditions, so that a temperature zone is formed at the edge of the pore plate in the heating and cooling process of the pore plate; that is to say, a temperature ring is formed by introducing the thickness change of the structure in the edge area of the pore plate, and the temperature ring is slightly higher than the temperature of the accommodating hole group during heating and slightly lower than the temperature of the accommodating hole group during cooling, so that the edge effect is effectively reduced, and the temperature of the edge area of the pore plate is closer to that of the central area; therefore, the uniformity of overall temperature distribution is improved.

Description

Technical Field

[0001] The invention relates to the field of PCR well plates, and in particular to a method for improving the temperature uniformity of a PCR well plate and a PCR well plate. Background Art

[0002] Real-time fluorescence quantitative polymerase chain reaction (PCR) technology has become one of the main means in molecular biology and medical research and clinical applications due to its real-time, sensitivity and specificity. In well-plate PCR, the temperature consistency between wells has a great impact on the amplification performance of the instrument. Especially for instruments with melting curve function, the step value of the temperature gradient is usually 0.15℃, and the temperature consistency between wells needs to be within 0.1℃ to ensure the accuracy of melting peak analysis. Therefore, improving temperature uniformity is the focus of PCR equipment research.

[0003] The temperature uniformity problem of well-plate PCR is a key factor affecting the accuracy and repeatability of experimental results. In well-plate PCR, temperature consistency between different wells is crucial, because large temperature differences between wells will lead to inconsistent amplification efficiency, thus affecting the experimental results. In addition, the temperature at the edge of the well plate is usually lower than that in the central area. This phenomenon is called the "edge effect", which further aggravates the uneven temperature distribution between wells. For instruments that collect fluorescence at the top, the Peltier can cover the entire heating area, so the temperature consistency is better, but the edge effect still exists. For instruments that collect fluorescence at the bottom, since the Peltier cannot be placed at the bottom of the well, the heat source can only be arranged on both sides or around the well, resulting in uneven heat source itself, poor heat conduction consistency, and more obvious edge effect.

[0004] In the traditional method of solving the problem of temperature uniformity of well plate PCR, a common way is to add an auxiliary heating device, such as a heating wire or a heating film, to the bottom edge of the well plate to form a main heating compensation device, while the middle temperature rise and fall structure is still Peltier as the main temperature change device. Patent CN_101974421_A proposes a compensation power calculation method, and constructs a one-variable first-order equation to calculate the compensation power through the empirical value obtained by empirical exploration. However, this method only solves the problem of temperature unevenness at a certain point, and does not consider the temperature characteristics of heat capacity and main control temperature change. In the cooling process, the compensation heating will aggravate the temperature drift of the heat dissipation system and increase the unstable parameters of the control system. Another method is to improve temperature uniformity by increasing the cooling area, but although this method is effective, it wastes area and increases power consumption, so it is not economical. For example, the rejected patent CN_102174386_A adopts this method. In addition, using water as a heat dissipation medium can change the heat conduction density load, thereby improving temperature uniformity, but due to the high heat capacity of water, this will sacrifice the heating rate. In summary, although these traditional methods have improved temperature uniformity to a certain extent, they each have their own limitations and fail to fully meet the needs of rapid temperature change and efficient uniformity. Summary of the invention

[0005] In order to solve the problem of how to improve temperature uniformity without reducing the heating and cooling speed, the present invention proposes a method for improving the temperature uniformity of a PCR well plate, comprising:

[0006] Construct the heat conduction differential equation through Fourier's law of heat conduction;

[0007] The first type of boundary condition is set according to the fixed temperature at the edge of the orifice plate; the second type of boundary condition is set according to the heat density on the edge of the orifice plate; the third type of boundary condition is set according to the convective heat transfer process between the edge of the orifice plate and the surrounding fluid;

[0008] The heat conduction differential equation is limited by the above three types of boundary conditions;

[0009] Based on the thermal conductivity of the orifice edge material, the orifice cross-sectional area perpendicular to the heat flow direction, and the temperature gradient, the calculation equations for unit heat and unit heat density are constructed in combination with the heat conduction differential equation; the temperature gradient represents the rate of change of temperature along the heat flow direction; the unit heat represents the amount of heat passing through a preset cross-sectional area per unit time; the unit heat density represents the amount of heat passing through a unit area per unit time;

[0010] The relationship between unit heat density and the thickness of the material at the edge of the orifice plate is determined by the calculation equation of unit heat and unit heat density, and based on this relationship, the influence of the thickness of the material at the edge of the orifice plate on the second type of boundary conditions is analyzed;

[0011] According to the correlation between unit heat density and the thickness of the orifice plate edge material and the analysis results of its influence on the second type of boundary conditions, the thickness of the orifice plate edge material is designed and set so that a temperature zone is formed at the edge of the orifice plate during the heating and cooling process.

[0012] Furthermore, the heat conduction differential equation is constructed through Fourier's heat conduction law, including:

[0013] The first formula is based on the fact that the heat conduction power per unit volume is equal to the heat source power per unit volume in steady-state heat transfer:

[0014] In the formula, Q represents the heat source power per unit volume, that is, the total heat passing through the preset cross-sectional area A per unit time; represents the heat flux vector; represents the divergence operation;

[0015] The second formula is set based on Fourier's law of heat conduction:

[0016] Where T is the temperature field, are the unit direction vectors in the x, y, and z directions respectively, k x ,k y ,k z are the thermal conductivity of the orifice edge material along the x, y, and z directions respectively;

[0017] Substituting the second formula into the first formula, we get the third formula:

[0018]

[0019] By expanding the third formula in the rectangular coordinate system, the heat conduction differential equation is obtained:

[0020]

[0021] Furthermore, the first type of boundary condition is used to set the temperature of the edge of the orifice plate, and its formula is: T 边缘 =T1; where T 边缘 represents the temperature on the edge of the orifice plate, and T1 represents the preset fixed temperature of the edge of the orifice plate;

[0022] The second type of boundary condition is used to specify the heat flux per unit area on the edge of the orifice plate, and its formula expression is:

[0023] In the formula, l x , l y , l z are the three components of the unit external normal vector on the edge of the orifice plate, indicating the direction of the edge of the orifice plate; q represents the unit heat density, that is, the amount of heat passing through a unit area per unit time;

[0024] The third type of boundary condition is used to limit the heat exchange between the edge of the orifice plate and the surrounding fluid, and its formula is:

[0025] Where, T ∞ express

[0026] The free stream temperature of the mainstream field at the edge of the orifice plate, T 表面 represents the temperature of the edge surface of the orifice plate, and h represents the convection heat transfer coefficient.

[0027] Furthermore, the calculation equation of the unit heat is: In the formula, A represents the cross-sectional area of ​​the orifice plate perpendicular to the direction of heat flow, Q represents the total heat passing through the preset cross-sectional area A per unit time, and λ represents the thermal conductivity of the orifice plate edge material. It represents the temperature gradient, that is, the rate of change of temperature along the direction of heat flow;

[0028] The calculation equation of the unit heat density is: In the formula, q represents the unit heat density, that is, the amount of heat passing through a unit area per unit time.

[0029] Furthermore, the relationship between the unit heat density and the thickness of the orifice plate edge material is determined by the calculation equation of the unit heat and the unit heat density, specifically:

[0030] A thickness modulation heat conduction model is constructed to reflect the effect of the thickness change of the orifice edge material on heat conduction. The x-axis coordinate of the thickness modulation heat conduction model is the thickness position of the orifice edge material, and the y-axis coordinate is the temperature T.

[0031] The thermal conductivity of the orifice edge material is set not to change with the change of the x-axis coordinate, and the total heat passing through the preset cross-sectional area A per unit time does not change with the x-axis coordinate. Integrate to get the integral formula: Wherein, x1 represents the starting position of the material thickness at the edge of the orifice plate, and x2 represents the ending position of the material thickness at the edge of the orifice plate; T1 and T2 represent the temperatures at the starting position and the ending position, respectively;

[0032] The correlation between unit heat density and the thickness of the orifice plate edge material is obtained by the integral formula: In the formula, δ = x2-x1; in the formula, δ represents the thickness of the material at the edge of the orifice plate.

[0033] The embodiment of the present invention further provides a PCR well plate, comprising:

[0034] An orifice plate body, wherein the orifice plate body is provided with an accommodating hole group, and the accommodating hole group includes a plurality of accommodating holes;

[0035] The orifice plate body is provided with first edge plates at both sides along the length direction of the accommodating hole group, and the orifice plate body is provided with second edge plates and third edge plates at both ends along the length direction of the accommodating hole group; the thickness of the second edge plates and the third edge plates are both smaller than that of the first edge plates;

[0036] The thickness ratio of the first edge plate, the second edge plate and the third edge plate is set by a method for improving the temperature uniformity of a PCR well plate as described in any one of claims 1 to 5.

[0037] Further, when the thickness ratio of the first edge plate, the second edge plate and the third edge plate is set to 3:2:1, the heat flow direction is toward the side where the third edge plate is located;

[0038] When the thickness ratio of the first edge plate, the second edge plate and the third edge plate is set to 3:1:2, the heat flow direction is toward the side where the second edge plate is located.

[0039] Further, the thickness of the second edge plate and the third edge plate are both greater than a preset threshold;

[0040] When the set thickness ratio does not satisfy the condition that the thickness of the second edge plate and the third edge plate are both greater than the preset threshold, the thickness relationship of the first edge plate, the second edge plate and the third edge plate is re-set based on the heat flow direction.

[0041] Further, the thickness relationship of the first edge plate, the second edge plate and the third edge plate is set based on the heat flow direction, specifically including:

[0042] When setting the heat flow direction toward the side where the second edge plate is located, set:

[0043] Preset threshold < thickness of the second edge plate < thickness of the third edge plate < thickness of the first edge plate;

[0044] When setting the heat flow direction toward the side where the third edge plate is located, set:

[0045] The preset threshold value < the thickness of the third edge plate < the thickness of the second edge plate < the thickness of the first edge plate.

[0046] Furthermore, the accommodating hole group includes a plurality of rows of accommodating holes, and Peltiers are provided on both sides of each row of accommodating holes;

[0047] Two ends of the Peltier extend from two ends of a corresponding row of receiving holes respectively.

[0048] Compared with the prior art, the present invention has at least the following beneficial effects:

[0049] (1) The present invention determines the relationship between unit heat density and the thickness of the orifice plate edge material through the calculation equation of unit heat and unit heat density, and analyzes the influence of the thickness of the orifice plate edge material on the second type of boundary conditions based on this relationship; according to the correlation between unit heat density and the thickness of the orifice plate edge material and the analysis results of its influence on the second type of boundary conditions, the thickness of the orifice plate edge material is designed and set so that a temperature zone is formed at the edge of the orifice plate during the heating and cooling process of the orifice plate; that is, the present invention forms a temperature ring by introducing a thickness change of the structure in the edge area of ​​the orifice plate. This temperature ring is slightly higher than the temperature of the accommodating hole group when heating up and slightly lower than the temperature of the accommodating hole group when cooling down. This design effectively reduces the edge effect and makes the temperature of the edge area of ​​the orifice plate closer to the central area, thereby improving the uniformity of the overall temperature distribution;

[0050] (2) The present invention does not require an independently installed auxiliary heating unit, and only requires the thickness of the structure to be changed at the edge of the orifice plate. This design is simple and easy to implement, reducing the complexity and manufacturing cost of the equipment;

[0051] (3) The present invention improves temperature uniformity while maintaining a rapid heating and cooling speed; this method ensures the consistency and stability of temperature during the rapid temperature change process, meeting the requirements of modern qPCR technology for efficient and rapid temperature change;

[0052] (4) Since no additional auxiliary heating unit is required, the present invention reduces unnecessary energy consumption while improving temperature uniformity; compared with traditional methods, such as increasing the cooling area or using high heat capacity water as the heat dissipation medium, the present invention reduces overall energy consumption while ensuring performance. BRIEF DESCRIPTION OF THE DRAWINGS

[0053] Figure 1 A flow chart of a method for improving the temperature uniformity of a PCR well plate;

[0054] Figure 2 This is the thickness modulation heat conduction model diagram;

[0055] Figure 3 Schematic diagram of the PCR plate structure;

[0056] Figure 4 This is a schematic diagram of the planar structure of a PCR well plate.

[0057] 1. First edge plate; 2. Second edge plate; 3. Third edge plate; 10. Accommodating hole group. DETAILED DESCRIPTION

[0058] The following are specific embodiments of the present invention and the accompanying drawings to further describe the technical solution of the present invention, but the present invention is not limited to these embodiments.

[0059] Embodiment 1

[0060] In order to ensure the consistency and stability of the temperature between wells during the rapid temperature change process and meet the requirements of modern PCR technology for efficient and rapid temperature change, such as Figure 1 As shown, an embodiment of the present invention provides a method for improving the temperature uniformity of a PCR well plate, comprising:

[0061] Construct the heat conduction differential equation through Fourier's law of heat conduction;

[0062] The heat conduction differential equation is constructed through Fourier's heat conduction law, including:

[0063] The first formula is based on the fact that the heat conduction power per unit volume is equal to the heat source power per unit volume in steady-state heat transfer:

[0064] In the formula, Q represents the heat source power per unit volume, that is, the total heat passing through the preset cross-sectional area A per unit time; represents the heat flux vector; represents the divergence operation;

[0065] The second formula is set based on Fourier's law of heat conduction:

[0066] Where T is the temperature field (the temperature field T describes the temperature at any point (x, y, z) inside the object), are the unit direction vectors in the x, y, and z directions respectively, k x ,k y ,k z are the thermal conductivity of the orifice edge material along the x, y, and z directions respectively;

[0067] Substituting the second formula into the first formula, we get the third formula:

[0068]

[0069] By expanding the third formula in the rectangular coordinate system, the heat conduction differential equation is obtained:

[0070]

[0071] The first type of boundary condition is set according to the fixed temperature at the edge of the orifice plate; the second type of boundary condition is set according to the heat density on the edge of the orifice plate; the third type of boundary condition is set according to the convective heat transfer process between the edge of the orifice plate and the surrounding fluid;

[0072] The first type of boundary condition is used to set the temperature of the edge of the orifice plate, and its formula is: T 边缘 =T1; where T 边缘represents the temperature on the edge of the orifice plate, and T1 represents the preset fixed temperature of the edge of the orifice plate;

[0073] The second type of boundary condition is used to specify the heat flux per unit area on the edge of the orifice plate, and its formula expression is:

[0074] In the formula, l x , l y , l z are the three components of the unit external normal vector on the edge of the orifice plate, indicating the direction of the edge of the orifice plate; q represents the unit heat density, that is, the amount of heat passing through a unit area per unit time;

[0075] The third type of boundary condition is used to limit the heat exchange between the edge of the orifice plate and the surrounding fluid, and its formula is:

[0076] Where, T ∞ express

[0077] The free stream temperature of the mainstream field at the edge of the orifice plate, T 表面 represents the temperature of the edge surface of the orifice plate, and h represents the convection heat transfer coefficient.

[0078] The heat conduction differential equation is limited by the above three types of boundary conditions;

[0079] Based on the thermal conductivity of the orifice edge material, the orifice cross-sectional area perpendicular to the heat flow direction, and the temperature gradient, the calculation equations for unit heat and unit heat density are constructed in combination with the heat conduction differential equation; the temperature gradient represents the rate of change of temperature along the heat flow direction; the unit heat represents the amount of heat passing through a preset cross-sectional area per unit time; the unit heat density represents the amount of heat passing through a unit area per unit time;

[0080] Since Fourier's law is the basic law of heat conduction, it states that the amount of heat per unit time is proportional to the temperature gradient and the cross-sectional area perpendicular to the direction of heat flow, therefore:

[0081] The calculation equation of the unit heat is: In the formula, A represents the cross-sectional area of ​​the orifice plate perpendicular to the direction of heat flow, Q represents the total heat passing through the preset cross-sectional area A per unit time, and λ represents the thermal conductivity of the orifice plate edge material. It represents the temperature gradient, that is, the rate of change of temperature along the direction of heat flow;

[0082] The physical meaning of the calculation equation for unit heat is: the total heat Q passing through the orifice cross-sectional area A is proportional to the orifice cross-sectional area, the thermal conductivity of the material and the temperature gradient. The negative sign indicates that the direction of heat flow is from high temperature to low temperature, that is, the direction of heat flow is opposite to the direction of temperature increase.

[0083] The calculation equation of the unit heat density is: In the formula, q represents unit heat density, that is, the amount of heat passing through a unit area per unit time. The negative sign in the formula indicates that the direction of heat flow is opposite to the direction of the temperature gradient.

[0084] The physical meaning of the calculation equation of unit heat density is that the amount of heat q passing through a unit area is proportional to the thermal conductivity of the material and the temperature gradient. Similarly, the negative sign indicates that the direction of heat flow is from high temperature to low temperature.

[0085] The relationship between unit heat density and the thickness of the material at the edge of the orifice plate is determined by the calculation equation of unit heat and unit heat density, and based on this relationship, the influence of the thickness of the material at the edge of the orifice plate on the second type of boundary conditions is analyzed;

[0086] The relationship between the unit heat density and the thickness of the material at the edge of the orifice plate is determined by the calculation equation of the unit heat and the unit heat density, specifically:

[0087] Build as Figure 2 The thickness modulation heat conduction model shown is used to reflect the influence of the thickness change of the orifice edge material on the heat conduction; the x-axis coordinate of the thickness modulation heat conduction model is the thickness position of the orifice edge material, and the y-axis coordinate is the temperature T;

[0088] The thermal conductivity λ of the orifice edge material does not change with the change of the x-axis coordinate, and the total heat Q passing through the preset cross-sectional area A per unit time does not change with the x-axis coordinate. Integrate to get the integral formula: Wherein, x1 represents the starting position of the material thickness at the edge of the orifice plate, and x2 represents the ending position of the material thickness at the edge of the orifice plate; T1 and T2 represent the temperatures at the starting position and the ending position, respectively (which are known fixed values);

[0089] The correlation between unit heat density and the thickness of the orifice plate edge material is obtained by the integral formula: In the formula, δ = x2-x1; in the formula, δ represents the thickness of the material at the edge of the orifice plate.

[0090] Figure 2 middle:

[0091] The red arrow indicates the direction of heat flow, and the isothermal surface is perpendicular to the direction of heat flow;

[0092] Q x With Q x+dx : represent the unit heat at the thickness position x and x+dx respectively, reflecting the distribution of heat in the material;

[0093] Δx represents a small increment in space and is used to describe the temperature gradient during heat conduction;

[0094] The temperature difference between T1 and T2 drives the conduction of heat. Heat is transferred from the high temperature area (T1) to the low temperature area (T2);

[0095] In this embodiment, it can be known from the integral formula that by reducing the thickness of the metal structure, the thermal conductivity coefficient and the thickness ratio λ / δ can be increased, thereby increasing the unit heat density q. This increase in q is not directly caused by the electric power, but is caused by the change in the heat conduction path. Specifically, when the metal thickness in the edge area of ​​the orifice plate is reduced, the heat conduction load density in the area increases, so that during the heating process, these thin areas will form a higher temperature zone than the thick areas. This temperature zone can prevent the internal temperature from being conducted to the edge, thereby improving the temperature uniformity of the internal area.

[0096] During the cooling process, these thin areas form a cold ring, and the heat in the internal area will be balanced toward the cold ring, avoiding the gradient cooling effect caused by the heat dissipation direction at the bottom. Although the increase in q will cause the temperature to rise, the amount of increase will be limited by the distribution of the entire temperature field, ensuring that the temperature change is within a controllable range. This design utilizes reverse thinking and does not change the thermal power density, but instead changes the mass distribution of the metal to achieve changes in the temperature field. This method not only simplifies the structural design, but also improves the uniformity and efficiency of temperature control, avoiding the complexity and instability caused by adding additional heat sources in traditional methods. In this way, the temperature uniformity problem in well plate qPCR can be effectively solved without adding additional heat sources.

[0097] According to the correlation between unit heat density and the thickness of the orifice plate edge material and the analysis results of its influence on the second type of boundary conditions, the thickness of the orifice plate edge material is designed and set so that a temperature zone is formed at the edge of the orifice plate during the heating and cooling process.

[0098] In this embodiment, the analysis result of the influence of the second type of boundary conditions is expressed by the following formula:

[0099]

[0100] In this embodiment, the edge of the orifice plate refers to the area surrounding the accommodating orifice group.

[0101] Existing patents usually solve the problem of temperature uniformity by adding heat sources, but this method has the instability of thermal convection and needs to be restricted. However, there is currently no visible patent that improves temperature uniformity by changing heat conduction. Assuming that the structure is made of metal with uniform mass, changing the thermal power density can cause changes in the thermal conduction density, thereby inducing changes in the boundary and temperature field. Using reverse thinking, the present invention does not change the thermal power density, but changes the mass distribution of the metal, which can also produce changes in the temperature field. Specifically, by thinning the metal structure in the edge area of ​​the orifice plate, the heat conduction load density in these areas is higher, thereby forming a temperature zone higher than the thick area when the temperature is raised, preventing the internal temperature from being conducted to the edge, and improving the temperature uniformity of the internal area. When cooling, these thin areas form a cold ring, and the heat in the internal area will be balanced to the cold ring, avoiding the gradient cooling effect caused by the heat dissipation direction at the bottom. This design not only simplifies the structure, but also improves the uniformity and efficiency of temperature control.

[0102] Embodiment 2

[0103] like Figure 3 and Figure 4 As shown, the embodiment of the present invention also provides a PCR well plate, comprising:

[0104] An orifice plate body, wherein the orifice plate body is provided with an accommodating hole group 10, and the accommodating hole group 10 includes a plurality of accommodating holes;

[0105] The orifice plate body is provided with first edge plates 1 on both sides along the length direction of the accommodating hole group 10, and the orifice plate body is provided with second edge plates 2 and third edge plates 3 on both ends along the length direction of the accommodating hole group 10; the thickness of the second edge plates 2 and the third edge plates 3 are both smaller than the first edge plate 1;

[0106] In this embodiment, a heat cover matching its size is also provided on the orifice plate body.

[0107] The thickness ratio of the first edge plate 1 , the second edge plate 2 and the third edge plate 3 is set by a method for improving the temperature uniformity of a PCR well plate as described in any one of claims 1 to 5.

[0108] When the thickness ratio of the first edge plate 1, the second edge plate 2 and the third edge plate 3 is set to 3:2:1, the heat flow direction is toward the side where the third edge plate 3 is located;

[0109] When the thickness ratio of the first edge plate 1 , the second edge plate 2 and the third edge plate 3 is set to 3:1:2, the heat flow direction is toward the side where the second edge plate 2 is located.

[0110] In this embodiment, Figure 4As shown, the area framed by green lines indicates the location where the Peltier is placed, the area framed by red lines indicates the generated temperature zone, and the arrows in the figure indicate the direction of heat flow.

[0111] In this embodiment, the thickness ratio of the first edge plate 1 , the second edge plate 2 , and the third edge plate 3 may also be set to 3:1:1 or 3:2:2.

[0112] The thickness of the second edge plate 2 and the third edge plate 3 are both greater than a preset threshold value; the purpose of such limitation is to avoid excessive thinning affecting the normal strength of the orifice plate base area, and to prevent the Peltier from burning due to thermal deformation caused by being too thin and unable to fit the Peltier. In addition, an overly thin edge plate will also cause a large temperature difference during the heating and cooling process, resulting in uneven heating and cooling inside the Peltier, thereby reducing its service life.

[0113] When the set thickness ratio does not satisfy the condition that the thickness of the second edge plate 2 and the third edge plate 3 are both greater than the preset threshold, the thickness relationship of the first edge plate 1, the second edge plate 2 and the third edge plate 3 is re-set based on the heat flow direction.

[0114] The thickness relationship between the first edge plate 1, the second edge plate 2 and the third edge plate 3 is set based on the heat flow direction, specifically including:

[0115] When the heat flow direction is set to the side where the second edge plate 2 is located, set:

[0116] Preset threshold < thickness of second edge plate 2 < thickness of third edge plate 3 < thickness of first edge plate 1;

[0117] When the heat flow direction is set toward the side where the third edge plate 3 is located, set:

[0118] The preset threshold value<the thickness of the third edge plate 3<the thickness of the second edge plate 2<the thickness of the first edge plate 1 .

[0119] The receiving hole group 10 includes a plurality of rows of receiving holes, and Peltiers are provided on both sides of each row of receiving holes;

[0120] Two ends of the Peltier extend from two ends of a corresponding row of receiving holes respectively.

[0121] like Figure 4 As shown, in order to offset the gradient effect, the Peltier in this embodiment extends nearly the length of a receiving hole, that is, a wider Peltier is arranged in the heat flow direction. This design generates a compensation temperature zone at both ends of the receiving hole group 10, thereby significantly improving the temperature consistency between the holes.

[0122] The present invention utilizes a part of the area of ​​the Peltier as a power element for edge compensation, but does not independently design an additional compensation heating channel, and does not significantly expand the heating area. By changing the thickness of the microstructure of the heating block (i.e., the area of ​​the orifice plate covered by the Peltier around the accommodating hole group), a change in the heat conduction density load is generated. Specifically, it is achieved by thinning the area of ​​the orifice plate covered by the Peltier around the accommodating hole group. Since the heat conduction load density is higher in the thin area of ​​the heat source, it will cause the temperature in this area to rise and fall faster. During the heating process, these thin areas will form a temperature belt / ring that is higher than the thick area. This temperature belt / ring can prevent the internal temperature from being conducted to the edge, thereby improving the temperature uniformity of the internal area. When cooling, this temperature ring becomes a cold ring, and the heat in the internal area will balance to the cold ring, avoiding the gradient cooling effect caused by the bottom heat dissipation direction. This design of forming a dynamic temperature compensation belt utilizes the principle of heat conduction density load change that the thin area at the heat source will heat or cool first, forming an effect similar to a compensation heating device (such as a heating rod or a heating film), but does not require additional control, and can automatically rise and fall synchronously with the internal temperature zone. This approach not only simplifies the design, but also improves the uniformity and efficiency of temperature control.

[0123] It should be noted that all directional indications in the embodiments of the present invention (such as up, down, left, right, front, back, etc.) are only used to explain the relative position relationship, movement status, etc. between the components under a certain specific posture (as shown in the accompanying drawings). If the specific posture changes, the directional indication will also change accordingly.

[0124] In addition, in the present invention, descriptions such as "first", "second", "one", etc. are only used for descriptive purposes and cannot be understood as indicating or implying their relative importance or implicitly indicating the number of the indicated technical features. Therefore, the features defined as "first" or "second" may explicitly or implicitly include at least one of the features. In the description of the present invention, the meaning of "plurality" is at least two, such as two, three, etc., unless otherwise clearly and specifically defined.

[0125] In the present invention, unless otherwise clearly specified and limited, the terms "connection", "fixation", etc. should be understood in a broad sense. For example, "fixation" 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, unless otherwise clearly defined. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0126] In addition, the technical solutions between the various embodiments of the present invention can be combined with each other, but it must be based on the fact that ordinary technicians in the field can implement it. When the combination of technical solutions is contradictory or cannot be implemented, it should be deemed that such combination of technical solutions does not exist and is not within the scope of protection required by the present invention.

Claims

1. A method for improving the temperature uniformity of a PCR well plate, characterized in that: include: Construct the heat conduction differential equation through Fourier's law of heat conduction; The first type of boundary condition is set according to the fixed temperature at the edge of the orifice plate; the second type of boundary condition is set according to the heat density on the edge of the orifice plate; the third type of boundary condition is set according to the convective heat transfer process between the edge of the orifice plate and the surrounding fluid; The heat conduction differential equation is limited by the above three types of boundary conditions; Based on the thermal conductivity of the orifice edge material, the orifice cross-sectional area perpendicular to the heat flow direction, and the temperature gradient, the calculation equations for unit heat and unit heat density are constructed in combination with the heat conduction differential equation; the temperature gradient represents the rate of change of temperature along the heat flow direction; the unit heat represents the amount of heat passing through a preset cross-sectional area per unit time; the unit heat density represents the amount of heat passing through a unit area per unit time; The relationship between unit heat density and the thickness of the material at the edge of the orifice plate is determined by the calculation equation of unit heat and unit heat density, and based on this relationship, the influence of the thickness of the material at the edge of the orifice plate on the second type of boundary conditions is analyzed; According to the correlation between unit heat density and the thickness of the orifice plate edge material and the analysis results of its influence on the second type of boundary conditions, the thickness of the orifice plate edge material is designed and set so that a temperature zone is formed at the edge of the orifice plate during the heating and cooling process.

2. A method for improving the temperature uniformity of a PCR plate according to claim 1, characterized in that: The heat conduction differential equation is constructed through Fourier's heat conduction law, including: The first formula is based on the fact that the heat conduction power per unit volume is equal to the heat source power per unit volume in steady-state heat transfer: In the formula, Q represents the heat source power per unit volume, that is, the total heat passing through the preset cross-sectional area A per unit time; represents the heat flux vector; represents the divergence operation; The second formula is set based on Fourier's law of heat conduction: Where T is the temperature field, are the unit direction vectors in the x, y, and z directions respectively, k x ,k y ,k z are the thermal conductivity of the orifice edge material along the x, y, and z directions respectively; Substituting the second formula into the first formula, we get the third formula: By expanding the third formula in the rectangular coordinate system, the heat conduction differential equation is obtained:

3. A method for improving the temperature uniformity of a PCR plate according to claim 2, characterized in that: The first type of boundary condition is used to set the temperature of the edge of the orifice plate, and its formula is: T 边缘 =T1; where T 边缘 represents the temperature on the edge of the orifice plate, and T1 represents the preset fixed temperature of the edge of the orifice plate; The second type of boundary condition is used to specify the heat flux per unit area on the edge of the orifice plate, and its formula expression is: In the formula, l x , l y , l z are the three components of the unit external normal vector on the edge of the orifice plate, indicating the direction of the edge of the orifice plate; q represents the unit heat density, that is, the amount of heat passing through a unit area per unit time; The third type of boundary condition is used to limit the heat exchange between the edge of the orifice plate and the surrounding fluid, and its formula is: Where, T ∞ represents the free stream temperature of the mainstream field at the edge of the orifice plate, T 表面 represents the temperature of the edge surface of the orifice plate, and h represents the convection heat transfer coefficient.

4. A method for improving the temperature uniformity of a PCR plate according to claim 3, characterized in that: The calculation equation of the unit heat is: In the formula, A represents the cross-sectional area of ​​the orifice plate perpendicular to the direction of heat flow, Q represents the total heat passing through the preset cross-sectional area A per unit time, and λ represents the thermal conductivity of the orifice plate edge material. It represents the temperature gradient, that is, the rate of change of temperature along the direction of heat flow; The calculation equation of the unit heat density is: In the formula, q represents the unit heat density, that is, the amount of heat passing through a unit area per unit time.

5. A method for improving the temperature uniformity of a PCR plate according to claim 4, characterized in that: The relationship between the unit heat density and the thickness of the material at the edge of the orifice plate is determined by the calculation equation of the unit heat and the unit heat density, specifically: A thickness modulation heat conduction model is constructed to reflect the effect of the thickness change of the orifice edge material on heat conduction. The x-axis coordinate of the thickness modulation heat conduction model is the thickness position of the orifice edge material, and the y-axis coordinate is the temperature T. The thermal conductivity of the orifice edge material is set not to change with the change of the x-axis coordinate, and the total heat passing through the preset cross-sectional area A per unit time does not change with the x-axis coordinate. Integrate to get the integral formula: Wherein, x1 represents the starting position of the material thickness at the edge of the orifice plate, and x2 represents the ending position of the material thickness at the edge of the orifice plate; T1 and T2 represent the temperatures at the starting position and the ending position, respectively; The correlation between unit heat density and the thickness of the orifice plate edge material is obtained by the integral formula: In the formula, δ = x2-x1; in the formula, δ represents the thickness of the material at the edge of the orifice plate.

6. A PCR well plate, characterized in that: include: An orifice plate body, wherein the orifice plate body is provided with an accommodating hole group, and the accommodating hole group includes a plurality of accommodating holes; The orifice plate body is provided with first edge plates at both sides along the length direction of the accommodating hole group, and the orifice plate body is provided with second edge plates and third edge plates at both ends along the length direction of the accommodating hole group; the thickness of the second edge plates and the third edge plates are both smaller than that of the first edge plates; The thickness ratio of the first edge plate, the second edge plate and the third edge plate is set by a method for improving the temperature uniformity of a PCR well plate as described in any one of claims 1 to 5.

7. A PCR well plate according to claim 6, characterized in that: When the thickness ratio of the first edge plate, the second edge plate and the third edge plate is set to 3:2:1, the heat flow direction is toward the side where the third edge plate is located; When the thickness ratio of the first edge plate, the second edge plate and the third edge plate is set to 3:1:2, the heat flow direction is toward the side where the second edge plate is located.

8. A PCR well plate according to claim 6, characterized in that: The thickness of the second edge plate and the third edge plate are both greater than a preset threshold; When the set thickness ratio does not satisfy the condition that the thickness of the second edge plate and the third edge plate are both greater than the preset threshold, the thickness relationship of the first edge plate, the second edge plate and the third edge plate is re-set based on the heat flow direction.

9. A PCR well plate according to claim 8, characterized in that: The thickness relationship of the first edge plate, the second edge plate and the third edge plate is set based on the heat flow direction, specifically including: When setting the heat flow direction toward the side where the second edge plate is located, set: Preset threshold < thickness of the second edge plate < thickness of the third edge plate < thickness of the first edge plate; When setting the heat flow direction toward the side where the third edge plate is located, set: The preset threshold value < the thickness of the third edge plate < the thickness of the second edge plate < the thickness of the first edge plate.

10. A PCR well plate according to claim 6, characterized in that: The receiving hole group includes a plurality of rows of receiving holes, and Peltiers are provided on both sides of each row of receiving holes; Two ends of the Peltier extend from two ends of a corresponding row of receiving holes respectively.

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