CN111898299A - An optimization method of PCR base manufacturing parameters based on numerical simulation of finite element model - Google Patents

An optimization method of PCR base manufacturing parameters based on numerical simulation of finite element model Download PDF

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CN111898299A
CN111898299A CN202010727847.5A CN202010727847A CN111898299A CN 111898299 A CN111898299 A CN 111898299A CN 202010727847 A CN202010727847 A CN 202010727847A CN 111898299 A CN111898299 A CN 111898299A
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李建兴
杨睿宁
罗堪
马莹
陈炜
黄靖
沈亮
蔡聪
赖智晨
刘肖
黄炳法
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Fujian Piaofutong Information Technology Co ltd
Fujian University Of Science And Technology
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Abstract

本发明涉及一种基于有限元模型数值仿真的PCR基座制造参数优化方法,通过常用有限元软件COMSOL Multiphysics及其with MATLAB接口,构建数值仿真方法,用瞬态分析的方法给出了PCR基座有限元模型实际温度控制过程,并以此结果进行制造参数优化设计,以保证PCR基座在实际热循环过程中能够取得最优的动态和静态性能。发明能够在满足PCR基座温度性能指标下,获得的优化制造参数,如保温材料最优尺寸等可用于指导实际基座加工,保证其在热循环过程中保持快速温度响应前提下具有良好的热均匀性。本发明能够为新型PCR基座的研发大幅节约了时间和物质上的成本。The invention relates to a method for optimizing the manufacturing parameters of a PCR base based on finite element model numerical simulation. A numerical simulation method is constructed through the commonly used finite element software COMSOL Multiphysics and its with MATLAB interface, and the PCR base is given by a transient analysis method. The finite element model is used to model the actual temperature control process, and the results are used to optimize the design of manufacturing parameters to ensure that the PCR base can achieve optimal dynamic and static performance during the actual thermal cycling process. The optimized manufacturing parameters obtained by the invention, such as the optimal size of the thermal insulation material, can be used to guide the actual pedestal processing under the condition that the temperature performance index of the PCR pedestal is satisfied, so as to ensure that it has good thermal performance under the premise of maintaining a rapid temperature response during the thermal cycle. uniformity. The invention can greatly save time and material cost for the research and development of new PCR bases.

Description

一种基于有限元模型数值仿真的PCR基座制造参数优化方法An optimization method of PCR base manufacturing parameters based on numerical simulation of finite element model

技术领域technical field

本发明涉及PCR基座温度性能优化设计技术领域,特别是一种基于有限元模型数值仿真的PCR基座制造参数优化方法。The invention relates to the technical field of PCR base temperature performance optimization design, in particular to a method for optimizing PCR base manufacturing parameters based on finite element model numerical simulation.

背景技术Background technique

传热性能是PCR基座设计关注的核心。目前,在PCR基座制造中,如何优化PCR基座参数是设计中的难点。通过实际加工和真实传热实验的方法存在周期长,大量浪费人力物力的缺点。已有的仿真优化设计方法,大部分针对PCR基座有限元模型温度均匀性的仿真。多数只关注了求解基座的稳态温度性能。同时这些模型和方法只是简单的实现了给定温度作为热源间的传热仿真,没有考虑系统传感滞后和控制环节对温度性能的影响。这些具有局限的模型和方法对对象的动态响应描述进度较差,不能精确的求解出基座的热场分布和反映94℃-55℃-72℃三温区循环中动态温度的变化情况。Heat transfer performance is a central concern in PCR pedestal design. At present, in the manufacture of PCR pedestal, how to optimize the parameters of the PCR pedestal is a difficult point in the design. The method of actual processing and real heat transfer experiment has the shortcomings of long cycle and a lot of waste of manpower and material resources. Most of the existing simulation optimization design methods are aimed at the simulation of the temperature uniformity of the finite element model of the PCR base. Most focus only on solving the steady-state temperature performance of the base. At the same time, these models and methods simply realize the heat transfer simulation between a given temperature as a heat source, and do not consider the influence of the system sensing lag and control link on the temperature performance. These limited models and methods have poor progress in describing the dynamic response of the object, and cannot accurately solve the thermal field distribution of the base and reflect the dynamic temperature changes in the three-temperature cycle of 94℃-55℃-72℃.

现有的提高PCR基座设计有以下几种方案:The existing design of improving PCR base has the following schemes:

(1)直接使用基座裸露进行反应(1) Directly use the base bare for reaction

(2)在PCR基座侧壁四周包覆30mm聚乙烯泡棉以消去侧壁对流换热提高温度均匀性,在96孔PCR基座中在给定温度为94℃时基座最高温与最低温温差可以由1.2℃提升至0.34℃。(2) Wrap 30mm polyethylene foam around the side wall of the PCR base to eliminate the convection heat transfer of the side wall and improve the temperature uniformity. In the 96-well PCR base, when the given temperature is 94 °C, the maximum temperature and the minimum temperature of the base are The temperature difference can be increased from 1.2°C to 0.34°C.

(3)在真空干燥箱中进行反应为循环过程提供一个稳定的内部环境,消去空气对流换热的影响。(3) Carrying out the reaction in a vacuum drying oven provides a stable internal environment for the circulation process and eliminates the influence of air convection heat transfer.

在上述方法中(1)裸露基座的方案虽然温度响应性最快,但基座与环境温度存在较快的热交换导致基座温度均匀性较差;(2)引入保温材料包裹虽然能够改善基座稳态热均匀性能,但如果不能正确选择合适的保温材料包裹设计参数,会降低基座的动态性,使其温度响应产生较大的滞后,升降温速率收到极大影响。是否采用保温材料包裹、包裹厚度是多少都是基座制造中需要解决的问题。(3)由于真空干燥箱的体积是有限的,当热源还需要外接电路来维持循环的情况以及当应的环境有特定需求时就无法实现在真空干燥箱中反应,而且这种方案对PCR基座就有了极大的局限性,难以将其对基层卫生部门普及化。传统采用实验的方法不仅时间周期长,很难找到最优设计,存在大量浪费人力物力的缺点。Among the above methods (1) although the solution with the bare base has the fastest temperature response, the rapid heat exchange between the base and the ambient temperature leads to poor temperature uniformity of the base; (2) although the introduction of thermal insulation material wrapping can improve the The steady-state thermal uniformity of the base, but if the appropriate design parameters of the insulation material package cannot be selected correctly, the dynamics of the base will be reduced, the temperature response will have a large lag, and the heating and cooling rate will be greatly affected. Whether to use thermal insulation material to wrap and what the thickness of the wrapping is are the problems that need to be solved in the base manufacturing. (3) Since the volume of the vacuum drying box is limited, when the heat source needs an external circuit to maintain the cycle and the corresponding environment has specific requirements, the reaction in the vacuum drying box cannot be realized. The seat has great limitations, and it is difficult to popularize it to the grass-roots health sector. The traditional method of using experiments not only has a long time period, but also it is difficult to find the optimal design, and has the disadvantage of wasting a lot of manpower and material resources.

术语解释:Terminology Explanation:

基座:一般选取导热性较好的金属材料,如铜、铝等材料使得热循环过程中热源温度能较好传递到基座表面Base: Generally, metal materials with good thermal conductivity are selected, such as copper, aluminum and other materials, so that the temperature of the heat source can be better transferred to the surface of the base during the thermal cycle.

制造参数:指的是PCR基座模型材料、尺寸、孔数、是否包覆保温材料、保温材料选型、厚度等一系列实体设计参数。Manufacturing parameters: Refers to a series of physical design parameters such as PCR base model material, size, number of holes, whether to coat thermal insulation materials, selection of thermal insulation materials, and thickness.

保温材料:根据实际温度循环期间选取耐热性能满足的材料(如泡棉、EVA、硅酸铝纤维、聚乙烯等),在循环过程中大幅减小基座温度受外界环境影响。Insulation material: According to the actual temperature cycle, materials with satisfactory heat resistance (such as foam, EVA, aluminum silicate fiber, polyethylene, etc.) are selected to greatly reduce the influence of the base temperature by the external environment during the cycle.

PCR:聚合酶链式反应(PCR)是一种用于放大扩增特定的DNA片段的分子生物学技术,它可看作是生物体外的特殊DNA复制,PCR的最大特点,是在变性(94℃)-退火(55℃)-引物延伸(72℃)三个过程循环下能将微量的DNA大幅增加。PCR: The polymerase chain reaction (PCR) is a molecular biology technique used to amplify specific DNA fragments. It can be regarded as a special DNA replication in vitro. The biggest feature of PCR is that it is denatured (94 ℃)-annealing (55℃)-primer extension (72℃) three process cycles can greatly increase the trace amount of DNA.

有限元:有限元法(FEM,Finite Element Method)是一种为求解偏微分方程边值问题近似解的数值技术。求解时对整个问题区域进行分解,每个子区域都成为简单的部分。Finite Element: The Finite Element Method (FEM) is a numerical technique for approximate solutions to boundary value problems of partial differential equations. When solving, the entire problem region is decomposed, and each subregion becomes a simple part.

发明内容SUMMARY OF THE INVENTION

有鉴于此,本发明的目的是提供一种基于有限元模型数值仿真的PCR基座制造参数优化方法,通过有限元模型数值分析的方法完成对PCR基座制造参数优化数据的求解,即能符合温度性能需求又大大降低了研发期间的各方面成本,也不受环境局限,具有较好的适应性。In view of this, the object of the present invention is to provide a method for optimizing the manufacturing parameters of the PCR base based on the numerical simulation of the finite element model. The temperature performance requirement has greatly reduced the cost of all aspects during the research and development period, and it is not limited by the environment and has better adaptability.

本发明采用以下方案实现:一种基于有限元模型数值仿真的PCR基座制造参数优化方法,包括以下步骤:The present invention adopts the following scheme to realize: a kind of PCR base manufacturing parameter optimization method based on finite element model numerical simulation, comprising the following steps:

步骤S1:进行基座3D模型设计:根据实际设计所需要孔数,大小进行PCR基座的3D模型绘制;Step S1: Design the 3D model of the base: draw the 3D model of the PCR base according to the number and size of holes required for the actual design;

步骤S2:初始化仿真条件;Step S2: Initialize simulation conditions;

步骤S3:进行有限元模型初始化条件设置及仿真;Step S3: setting and simulating the initialization conditions of the finite element model;

步骤S4:进行优化方法设置,并判断是否符合约束条件,若符合则继续执行步骤S5,否则更新变量并返回步骤S3;Step S4: set the optimization method, and judge whether the constraint conditions are met, if so, continue to execute step S5, otherwise update the variables and return to step S3;

步骤S5:保存结果O1k{0<k≤n2︱k∈Z}至优化集O;Step S5: save the result O 1k {0<k≤n 2 ︱k∈Z} to the optimization set O;

步骤S6:判断是否符合停止条件式(1)、式(2),若符合则输出优化集O,并进行优化结果处理,完成PCR基座制造参数优化,否则更新变量并返回步骤S3;Step S6: judging whether the stop condition formula (1) and formula (2) are met, if so, output the optimization set O, and carry out the optimization result processing to complete the optimization of the manufacturing parameters of the PCR base, otherwise update the variables and return to step S3;

进一步地,所述步骤S2具体包括以下步骤:Further, the step S2 specifically includes the following steps:

步骤S21:初始化PCR基座静态和动态指标作为约束条件,稳态误差为ess,超调量为σ,升温速率为vup,降温速率为vdown,温度均匀性系数为ξ;Step S21: initialize the static and dynamic indicators of the PCR base as constraints, the steady-state error is ess , the overshoot is σ, the heating rate is v up , the cooling rate is v down , and the temperature uniformity coefficient is ξ;

稳态误差ess=a,超调量σ=b,升温速率vup=c,降温速率vdown=d,温度均匀性系数ξ=f;而在有限元仿真中其约束条件如式(1):Steady-state error ess = a, overshoot σ = b, heating rate v up = c, cooling rate v down = d, temperature uniformity coefficient ξ = f; and the constraints in the finite element simulation are as follows (1 ):

ess≤a、σ≤b、vup≥c、vdown≥d、ζ≤f (1)e ss ≤a, σ≤b, v up ≥c, v down ≥d, ζ≤f (1)

其中a、b、c、d、f均表示设计指标系数;根据现有PCR基座性能完成对指标系数的制定:0≤a≤0.5,0≤b≤10%,2℃/s≤vup≤4℃/s,1.5℃/s≤vdownn≤3℃/s,0.4≤ξ≤1;Among them, a, b, c, d, and f all represent the design index coefficient; according to the performance of the existing PCR base, the index coefficient is formulated: 0≤a≤0.5, 0≤b≤10%, 2℃/s≤v up ≤4℃/s, 1.5℃/s≤v downn ≤3℃/s, 0.4≤ξ≤1;

步骤S22:初始化待优化制造参数为变量V1、V2、V3…Vn,其中,V1代指基座制造材料类型、V2代指保温材料类型、V3代指保温材料厚度,V4…Vn代指包括基座尺寸,试管孔大小,表面是否开凿梅花孔对PCR基座可能有影响的参数;根据实际材料类型的选择来设定变量对应的步长;Step S22: Initialize the manufacturing parameters to be optimized as variables V 1 , V 2 , V 3 . . . V n , wherein V 1 refers to the type of base manufacturing material, V 2 refers to the type of thermal insulation material, and V 3 refers to the thickness of thermal insulation material, V 4 ...Vn refers to the parameters including the size of the base, the size of the test tube hole, and whether the surface of the plum blossom hole may have an impact on the PCR base; the step size corresponding to the variable is set according to the actual material type selection;

步骤S23:进行传感的实现及控制方法的选择,通过在PCR基座任一侧壁中点添加域点探针ppb1测量实时温度传感作为所采用控制算法的输入,控制方法则能够采用包括PID控制、模糊控制、内模控制或Smith预估控制智能控制算法作为系统控制方案;Step S23: Carry out the realization of sensing and the selection of the control method, by adding the domain point probe ppb1 to the midpoint of any side wall of the PCR base to measure the real-time temperature sensing as the input of the adopted control algorithm, and the control method can include: PID control, fuzzy control, internal model control or Smith predictive control intelligent control algorithm as the system control scheme;

步骤S24:根据实际制造成本制定优化性价比系数θ,初始化优化性价比系数θ,其表达式如式(2),根据制造成本定义变量V1、V2、V3、…、Vn的权重系数P1、P2、P3、…、PnStep S24: formulate the optimized cost-effectiveness coefficient θ according to the actual manufacturing cost, initialize the optimized cost-effectiveness coefficient θ, whose expression is as in formula (2), and define the weight coefficients P of the variables V 1 , V 2 , V 3 , . . . , V n according to the manufacturing cost 1 , P 2 , P 3 , ..., P n ;

θ=P1×V1+P2×V2+P3×V3+…+Pn×Vn (2)θ=P 1 ×V 1 +P 2 ×V 2 +P 3 ×V 3 +…+P n ×V n (2)

步骤S25:初始化停止条件及仿真搜索次数;设定停止条件如下:运行迭代次数达到最大迭代次数:n1>n2 Step S25: Initialize the stop condition and the number of simulation searches; set the stop condition as follows: the number of running iterations reaches the maximum number of iterations: n 1 >n 2

目标函数F下降梯度收敛:即Fk-Fk-1<TThe objective function F descends the gradient convergence: that is, F k -F k-1 <T

其中,n1为此时制造参数优化数据寻优迭代次数、n2为根据实际优化过程中计算资源所制定的最大数据寻优迭代次数,取500~10000。Fk表示k次迭代计算得到的目标值,T是设定的阈值常量,设为10-6Among them, n 1 is the number of optimization iterations of the manufacturing parameter optimization data at this time, and n 2 is the maximum number of iterations of data optimization based on the computing resources in the actual optimization process, taking 500 to 10,000. F k represents the target value calculated by k iterations, and T is the set threshold constant, which is set to 10 -6 .

进一步地,所述步骤S3的具体内容为:Further, the specific content of the step S3 is:

步骤S31:进行3D模型的设置:Step S31: Set the 3D model:

将所绘制的裸基座模型导入COMSOLMultiphysics其为C4,于COMSOLMultiphysics中绘制三个长方体C1、C2、C3;其中C1、C2、C3与从外部导入的裸基座C4的长宽高分别为(a1,b1,c1)、(a2,b2,c2)、(a3,b3,c3)、(a4,b4,c4);令C1、C2的中心点座标(x1,y1,z1)、(x2,y2,z2)与C4中心点座标(x4,y4,z4)一致,而C3中心点座标为(x4,,y4,z4+0.5c3+0.5c4),而其关系式如式(3)所示:Import the drawn bare pedestal model into COMSOL Multiphysics as C 4 , and draw three rectangular parallelepipeds C 1 , C 2 , C 3 in COMSOL Multiphysics; among them C 1 , C 2 , C 3 and the bare pedestal C 4 imported from outside The length, width and height are respectively (a 1 , b 1 , c 1 ), (a 2 , b 2 , c 2 ), (a 3 , b 3 , c 3 ), (a 4 , b 4 , c 4 ); Let the coordinates of the center point (x 1 , y 1 , z 1 ) and (x 2 , y 2 , z 2 ) of C 1 and C 2 agree with the coordinates of the center point of C 4 (x 4 , y 4 , z 4 ) , and the coordinates of the center point of C 3 are (x 4 , y 4 , z 4 +0.5c 3 +0.5c 4 ), and its relational expression is shown in formula (3):

a1≥a2=a4,b1≥b2=b4,c1=c2=c4,(a1-a2)=(b1-b2) (3)a 1 ≥a 2 =a 4 , b 1 ≥b 2 =b 4 , c 1 =c 2 =c 4 , (a 1 -a 2 )=(b 1 -b 2 ) (3)

其中(a3,b3,c3)根据选用热源尺寸进行设置,故2*(a1-a2)为保温材料的厚度;令C1和C2形成差集C5即为在基座四周包覆的保温材料并对C3、C4、C5构建联合体则形成一个裸基座四周包覆保温材料底部放置热源的PCR基座有限元几何模型;其中,所述C3表示热源,C4表示裸基座,C5表示保温材料;Among them (a 3 , b 3 , c 3 ) are set according to the size of the selected heat source, so 2*(a 1 -a 2 ) is the thickness of the thermal insulation material; let C 1 and C 2 form a difference set C 5 is the base The thermal insulation material covered around it and the combination of C 3 , C 4 , and C 5 are constructed to form a PCR base finite element geometric model with a heat source placed at the bottom of the bare base surrounded by the thermal insulation material; wherein, the C 3 represents the heat source. , C 4 represents the bare base, C 5 represents the thermal insulation material;

步骤S32:对PCR基座传热模型进行分析,在COMSOL Multiphy sics传热模块中选用能够实现PCR基座温度场特性的物理场进行有限元数值仿真:Step S32: Analyze the heat transfer model of the PCR base, and select a physical field that can realize the temperature field characteristics of the PCR base in the COMSOL Multiphysics heat transfer module to perform finite element numerical simulation:

由于PCR基座形状复杂且无内热源,故其导热问题用在笛卡尔坐标系中稳态、无内热源条件下导热微分方程进行描述,如式(4)所示:Due to the complex shape of the PCR base and no internal heat source, its thermal conductivity problem is described by a differential equation of thermal conductivity in the Cartesian coordinate system under the condition of steady state and no internal heat source, as shown in formula (4):

Figure BDA0002601863420000061
Figure BDA0002601863420000061

基座稳态热分析边界条件包括:基座底面的第一类边界条件、基座侧壁的对流换热第三类边界条件;由于基座底面与热源进行接触,故当温度升/降到恒定值时,基座底面与热源的接触面保持恒定温度,基座侧壁与空气存在自然对流换热,其边界条件如式(5)所示:The boundary conditions for steady-state thermal analysis of the base include: the first type of boundary conditions on the bottom of the base, and the third type of boundary conditions for convection heat transfer on the sidewall of the base; because the base bottom is in contact with the heat source, when the temperature rises/drops to When the value is constant, the contact surface between the bottom surface of the base and the heat source maintains a constant temperature, and there is natural convection heat exchange between the side wall of the base and the air. The boundary conditions are shown in formula (5):

Figure BDA0002601863420000062
Figure BDA0002601863420000062

其中,tw为基座温度,tf为周围空气温度,h为对流换热系数,λ0为热传导系数,n为基座侧壁法向方向;对于PCR基座温度控制是通过对其底部设置的热源发热量P以基座侧壁测点ppb1作为输入对热源发热功率P进行控制并将热量传递到PCR基座完成变温循环;通过对P CR基座温度场分析得出采用COMSOL Multiphysics中传热模块中的固体传热物理场用以完成有限元数值仿真;Among them, t w is the base temperature, t f is the ambient air temperature, h is the convective heat transfer coefficient, λ 0 is the thermal conductivity coefficient, and n is the normal direction of the base side wall; The heat source P of the set heat source takes the measurement point ppb1 on the side wall of the base as the input to control the heat power P of the heat source and transfers the heat to the PCR base to complete the temperature change cycle; The solid heat transfer physics in the heat transfer module is used to complete the finite element numerical simulation;

步骤S33:在固体传热物理场中完成对基座、热源、保温材料的材料类型及参数设置;Step S33: Complete the material type and parameter settings for the base, heat source, and thermal insulation material in the solid heat transfer physical field;

利用COMSOL Multiphysics中内置的材料库直接进行搜索或自行定义一个空材料,需要键入材料的恒压热容Cp[J/(kg·K)]、导热系数λ0[W/(m·K)]和密度ρ(kg/m3);Use the built-in material library in COMSOL Multiphysics to search directly or define an empty material by yourself, you need to enter the constant pressure heat capacity C p [J/(kg·K)], thermal conductivity λ 0 [W/(m·K) ] and density ρ (kg/m 3 );

步骤S34:在固体传热物理场中设置探针和热源热耗率设置:Step S34: Set the probe and heat source heat consumption rate settings in the solid heat transfer physics field:

在PCR基座任一侧壁布置温度传感器并在侧壁中心位置增加一域点探针ppb1;根据所选用的控制算法包括备选的PID控制、模糊控制、内模控制或Smith预估控制智能控制算法完成对热源发热功率P的控制以改变热源热耗率Q的大小实现三温区循环控制;热源热耗率Q表达式如式(6)所示:Arrange a temperature sensor on either side wall of the PCR base and add a domain point probe ppb 1 at the center of the side wall; according to the selected control algorithm, it includes alternative PID control, fuzzy control, internal model control or Smith prediction control The intelligent control algorithm completes the control of the heat source heating power P to change the size of the heat source heat consumption rate Q to realize the three-temperature zone cycle control; the heat source heat consumption rate Q expression is shown in formula (6):

Figure BDA0002601863420000071
Figure BDA0002601863420000071

其中,P为热源功率,V为热源体积;Among them, P is the heat source power, V is the heat source volume;

步骤S35:在固体传热物理场中进行边界条件的设置:Step S35: Set the boundary conditions in the solid heat transfer physics field:

设定基座侧壁与空气所存在的自然对流换热,若是裸基座则基座侧壁与空气存在自然对流换热,无需如式(5)进行计算,在COMSOL Multiphysics热通量模块中选择外部自然对流换热,垂直壁,需键入壁高度L(m)、外部温度Text(K)、绝对压力PA(Pa)并将流体种类选择为空气;若是基座侧壁存在保温材料,则其侧壁与空气存在自然对流换热可忽略不计,故保温材料侧壁温度定义为室温T0即可;基座上表面由于实际PCR基座反应过程中会放置104℃左右的恒温热盖防止试剂的挥发,故上表面视为绝热;Set the natural convection heat exchange between the sidewall of the base and the air. If the base is bare, there is a natural convection heat transfer between the sidewall of the base and the air. There is no need to perform the calculation as in Equation (5). In the COMSOL Multiphysics Heat Flux Module Select external natural convection heat transfer, vertical wall, need to enter wall height L (m), external temperature T ext (K), absolute pressure P A (Pa) and select the fluid type as air; if there is thermal insulation material on the side wall of the base , the natural convection heat exchange between the side wall and the air can be ignored, so the temperature of the side wall of the thermal insulation material can be defined as room temperature T 0 ; the upper surface of the base will be placed with a constant temperature of about 104°C during the actual PCR base reaction process. The cover prevents the volatilization of the reagent, so the upper surface is regarded as adiabatic;

对于网格的划分:使用对几何适应性最好的自由四面体进行网格的划分;由于PCR基座中在试管孔部分为形状较为复杂的环节,为节省计算资源先创建一个自由四面体网格进行全局绘制,再通过细化功能对试管孔面及其连接处进行细化,完成网格绘制;For mesh division: use the free tetrahedron with the best geometric adaptability for mesh division; since the test tube hole in the PCR base is a complex part of the shape, in order to save computing resources, first create a free tetrahedron mesh The grid is drawn globally, and then the hole surface of the test tube and its connections are refined through the refinement function to complete the grid drawing;

步骤S36:在固体传热物理场中进行求解器的配置:选择瞬态求解器,对求解器相对容差设为0.01;时间步进方法选为广义α,采用步长选为中级,代数变量设置中一致初始化选用向后欧拉法,初始步长分数为0.001.完成求解器配置,并保存文件,格式另存为.m格式为后续调用with Matlab接口做准备;Step S36: Configure the solver in the solid heat transfer physics field: select the transient solver, set the relative tolerance to the solver as 0.01; select the time step method as generalized α, select the step size as the intermediate level, and select the algebraic variable In the settings, the backward Euler method is selected for consistent initialization, and the initial step fraction is 0.001. Complete the solver configuration, and save the file in .m format to prepare for subsequent calls to the with Matlab interface;

步骤S37:在固体传热物理场中进行有限元数值仿真:根据所设置的有限元模型进行数值仿真,得到PCR基座热交换过程动态热场分布,并通过计算域点探针ppb1温度值曲线稳态误差ess、超调量σ升降、温速率vup、vdown,并根据式(2)计算优化性价比系数ξ,将所有结果保存为输出O1k{V1、V2、V3…Vn、essk、σk、vupk、vdownk、ξk、θk}{0<k≤n2︱k∈Z}。Step S37: carry out finite element numerical simulation in the solid heat transfer physical field: carry out numerical simulation according to the set finite element model, obtain the dynamic thermal field distribution of the heat exchange process of the PCR base, and calculate the temperature value curve of the domain point probe ppb1 by calculating Steady-state error ess , overshoot σ rise and fall, temperature rate v up , v down , and calculate the optimized cost performance coefficient ξ according to formula (2), and save all the results as output O 1k {V 1 , V 2 , V 3 … V n , essk , σ k , v upk , v downk , ξ k , θ k }{0<k≤n 2 ︱k∈Z}.

进一步地,所述步骤S4的具体内容为:Further, the specific content of the step S4 is:

利用COMSOL Multiphysics生成步骤S35中设置好的有限元模型的.m文件使用with MATLAB接口对.m文件进行式(1)为约束条件,S25中(1)、(2)为停止条件,搜索次数为n2,T是设定的阈值常量的定义;根据设定的搜索策略实现每次在(2)中变量V1、V2、V3的选定下步骤S36中计算结果O1k{V1、V2、V3…Vn、essk、σk、vupk、vdownk、ξk、θk}{0<k≤n2︱k∈Z}输出;判定是否满足停止迭代条件(1)、(2),若是则退出循环进入步骤S5;否则根据式(1)约束,更新新的仿真参数输入步骤S3重新进行有限元数值仿真。Use COMSOL Multiphysics to generate the .m file of the finite element model set in step S35. Use the with MATLAB interface to perform the .m file on the .m file. Formula (1) is the constraint condition, (1) and (2) in S25 are the stopping conditions, and the number of searches is n 2 , T is the definition of the set threshold constant; according to the set search strategy, each time the variables V 1 , V 2 , V 3 in (2) are selected, the calculation result O 1k {V 1 in step S36 is realized , V 2 , V 3 ... V n , essk , σ k , v upk , v downk , ξ k , θ k }{0<k≤n 2 ︱k∈Z} output; determine whether the stop iteration condition (1 ), (2), if so, exit the loop and go to step S5; otherwise, according to the constraint of formula (1), update the new simulation parameters and input step S3 to perform the finite element numerical simulation again.

进一步地,所述设定的搜索策略包括网格搜索、粒子群算法、模拟退火或蚁群算法。Further, the set search strategy includes grid search, particle swarm algorithm, simulated annealing or ant colony algorithm.

进一步地,所述步骤S6的具体内容为:判断是否满足停止条件式(1)、(2),若满足则停止计算,输出优化集合O{V1、V2、V3…Vn、ess、σ、vup、vdown、ξ、θ},并进行优化结果处理,完成PCR基座制造参数优化;否则更新变量返回步骤S3。Further, the specific content of the step S6 is: judging whether the stopping conditional expressions (1) and (2) are satisfied, if it is satisfied, stop the calculation, and output the optimization set O{V 1 , V 2 , V 3 . . . V n , e ss , σ, v up , v down , ξ, θ}, and process the optimization results to complete the optimization of the manufacturing parameters of the PCR base; otherwise, update the variables and return to step S3.

进一步地,所述优化结果处理的具体内容为:Further, the specific content of the optimization result processing is:

根据计算结果,将所有符合式(1)的输出值O1k{V1、V2、V3…Vn、essk、σk、vupk、vdownk、ξk、θk}{0<k≤n2︱k∈Z}输入集合O,根据θk{0<k≤n2︱k∈Z}从大到小的方式进行集合的重新排序,输出集合O提交给用户;根据用户定制的优化原则,在集合O中根据实际需求即当希望性价比更高则根据其性价比系数θ作为选择主要依据,若希望有更好的温度均匀性则以均匀性系数ξ作为选择的主要依据,同理希望有更快的升降温速率则考虑vupk、vdownk,希望有更好的温度精度则需要优先考虑ess、σ最小化。According to the calculation result, all output values O 1k {V 1 , V 2 , V 3 . . . V n , essk , σ k , v upk , v downk , ξ k , θ k }{0< k≤n 2 ︱k∈Z} input set O, reorder the set from large to small according to θ k {0<k≤n 2 ︱k∈Z}, and submit the output set O to the user; customized according to the user In the set O, according to the actual demand, that is, when you want to be more cost-effective, the cost-effectiveness coefficient θ is used as the main basis for selection. If you want better temperature uniformity, the uniformity coefficient ξ is used as the main basis for selection. The same Ideally, if a faster heating and cooling rate is desired, v upk and v downk should be considered. If better temperature accuracy is desired, ess and σ minimization should be prioritized.

与现有技术相比,本发明具有以下有益效果:Compared with the prior art, the present invention has the following beneficial effects:

(1)本发明通过有限元模型数值分析的方法完成对PCR基座制造参数优化数据的求解,即能符合温度性能需求又大大降低了研发期间的各方面成本,也不受环境局限,具有较好的适应性。(1) The present invention completes the solution of the optimization data of the manufacturing parameters of the PCR base through the method of numerical analysis of the finite element model, which can meet the temperature performance requirements and greatly reduce the cost of various aspects during the research and development period, and is not limited by the environment, and has a relatively high performance. good adaptability.

(2)本发明解决了以往PCR基座有限元模型数值仿真仅仅通过对稳态分析研究如何改善温度均匀性的问题,本发明可以直接观察PCR基座温度动静态性能并作出分析。(2) The present invention solves the problem that the numerical simulation of the finite element model of the PCR base only studies how to improve the temperature uniformity through steady-state analysis. The present invention can directly observe and analyze the temperature dynamic and static performance of the PCR base.

(3)本发明将传感和控制加入有限元数值仿真中,使得仿真极为逼近真实环境,使得仿真结果对实际研发具有极大指导意义。(3) The present invention adds sensing and control to the finite element numerical simulation, so that the simulation is very close to the real environment, and the simulation results have great guiding significance for actual research and development.

附图说明Description of drawings

图1为本发明实施例的方法流程图。FIG. 1 is a flowchart of a method according to an embodiment of the present invention.

图2为本发明实施例的升降温阶跃曲线图。FIG. 2 is a step curve diagram of heating and cooling according to an embodiment of the present invention.

图3为本发明实施例的96孔PCR基座工程图。FIG. 3 is an engineering drawing of a 96-well PCR base according to an embodiment of the present invention.

图4为本发明实施例的初始化仿真条件流程图。FIG. 4 is a flowchart of an initialization simulation condition according to an embodiment of the present invention.

图5为本发明实施例的有限元初始化条件设置流程图。FIG. 5 is a flow chart of setting a finite element initialization condition according to an embodiment of the present invention.

图6为本发明实施例的96孔座PCR基座设计工程图。FIG. 6 is a design engineering diagram of a 96-well PCR base according to an embodiment of the present invention.

图7为本发明实施例的96孔座PCR基座有限元几何模型图。FIG. 7 is a diagram of a finite element geometric model of a 96-well base PCR base according to an embodiment of the present invention.

图8为本发明实施例的96孔PCR基座网格划分示例图。FIG. 8 is an example diagram of grid division of a 96-well PCR base according to an embodiment of the present invention.

图9为本发明实施例的96孔PCR基座制造参数优化方法流程图。FIG. 9 is a flowchart of a method for optimizing manufacturing parameters of a 96-well PCR base according to an embodiment of the present invention.

图10为本发明实施例的96孔PCR基座制造参数优化后给定94℃时稳态热场图。FIG. 10 is a steady-state thermal field diagram at a given temperature of 94° C. after optimization of the manufacturing parameters of the 96-well PCR base according to the embodiment of the present invention.

图11为本发明实施例的96孔PCR基座制造参数优化后给定72℃时稳态热场图。FIG. 11 is a steady-state thermal field diagram at a given 72° C. after optimization of the manufacturing parameters of the 96-well PCR base according to the embodiment of the present invention.

图12为本发明实施例的96孔PCR基座制造参数优化后给定55℃时稳态热场图12 is a steady-state thermal field diagram at a given temperature of 55° C. after optimization of the manufacturing parameters of the 96-well PCR base according to the embodiment of the present invention

图13为本发明实施例的96孔PCR基座制造参数优化后测点温度动态曲线图。FIG. 13 is a dynamic curve diagram of the temperature of the measuring point after the manufacturing parameters of the 96-well PCR base are optimized according to the embodiment of the present invention.

具体实施方式Detailed ways

下面结合附图及实施例对本发明做进一步说明。The present invention will be further described below with reference to the accompanying drawings and embodiments.

应该指出,以下详细说明都是例示性的,旨在对本申请提供进一步的说明。除非另有指明,本文使用的所有技术和科学术语具有与本申请所属技术领域的普通技术人员通常理解的相同含义。It should be noted that the following detailed description is exemplary and intended to provide further explanation of the application. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs.

需要注意的是,这里所使用的术语仅是为了描述具体实施方式,而非意图限制根据本申请的示例性实施方式。如在这里所使用的,除非上下文另外明确指出,否则单数形式也意图包括复数形式,此外,还应当理解的是,当在本说明书中使用术语“包含”和/或“包括”时,其指明存在特征、步骤、操作、器件、组件和/或它们的组合。It should be noted that the terminology used herein is for the purpose of describing specific embodiments only, and is not intended to limit the exemplary embodiments according to the present application. As used herein, unless the context clearly dictates otherwise, the singular is intended to include the plural as well, furthermore, it is to be understood that when the terms "comprising" and/or "including" are used in this specification, it indicates that There are features, steps, operations, devices, components and/or combinations thereof.

如图1所示,本实施例提供一种基于有限元模型数值仿真的PCR基座制造参数优化方法,包括以下步骤:As shown in FIG. 1 , the present embodiment provides a method for optimizing the manufacturing parameters of a PCR base based on finite element model numerical simulation, including the following steps:

步骤S1:进行基座3D模型设计:根据实际设计所需要孔数,大小进行PCR基座的3D模型绘制;Step S1: Design the 3D model of the base: draw the 3D model of the PCR base according to the number and size of holes required for the actual design;

步骤S2:初始化仿真条件;Step S2: Initialize simulation conditions;

步骤S3:进行有限元模型初始化条件设置及仿真;Step S3: setting and simulating the initialization conditions of the finite element model;

步骤S4:进行优化方法设置,并判断是否符合约束条件,若符合则继续执行步骤S5,否则更新变量并返回步骤S3;Step S4: set the optimization method, and judge whether the constraint conditions are met, if so, continue to execute step S5, otherwise update the variables and return to step S3;

步骤S5:保存结果O1k{0<k≤n2︱k∈Z}至优化集O;Step S5: save the result O 1k {0<k≤n 2 ︱k∈Z} to the optimization set O;

步骤S6:判断是否符合停止条件式(1)、式(2),若符合则输出优化集O,并进行优化结果处理,完成PCR基座制造参数优化,否则更新变量并返回步骤S3;Step S6: judging whether the stop condition formula (1) and formula (2) are met, if so, output the optimization set O, and carry out the optimization result processing to complete the optimization of the manufacturing parameters of the PCR base, otherwise update the variables and return to step S3;

如图4所示,在本实施例中,所述步骤S2具体包括以下步骤:As shown in FIG. 4 , in this embodiment, the step S2 specifically includes the following steps:

步骤S21:将给出的PCR基座静态和动态设计指标作为约束条件,令温度传感测点ppb1点(其位置如图396孔PCR基座工程图中所示,以实际PCR基座为基准将其布置在传感器任一侧壁面取一中心点。)初始化PCR基座静态和动态指标作为约束条件,稳态误差为ess,超调量为σ,升温速率为vup,降温速率为vdown,温度均匀性系数为ξ;Step S21: Take the given PCR base static and dynamic design indicators as constraints, make the temperature sensing point ppb1 (the position of which is shown in the 396-well PCR base engineering drawing, and take the actual PCR base as the benchmark) Arrange it on any side wall of the sensor and take a center point.) Initialize the static and dynamic indicators of the PCR base as constraints, the steady-state error is ess , the overshoot is σ, the heating rate is v up , and the cooling rate is v down , the temperature uniformity coefficient is ξ;

稳态误差ess=a,超调量σ=b,升温速率vup=c,降温速率vdown=d,温度均匀性系数ξ=f;如图2所示,是一段升降温阶跃曲线图,其中T1、T4分别是升温区间和降温区间的给定目标温度值,T2、T5为升降温区间稳态温度值,稳态误差ess是指的是目标温度值与稳态温度值的差,升温区间稳态误差为essup=T1-T2,降温区间稳态误差为essdown=T5-T4。超调量指的是被调参数动态偏离给定值的最大程度,其中T3、T6分别为升降温区间动态偏离最高温度值,因此升温区间超调量

Figure BDA0002601863420000121
而降温区间超调量
Figure BDA0002601863420000122
升降温速率指的是从起始值到第一次达到给定温度值时温度变化速率,其中t1为升温时间,t2为降温时间,ΔT1、ΔT2为升降温期间温度变化量,由于本示意图起始温度为20,故ΔT1=T1-20,ΔT2=T4-T2则升温速率
Figure BDA0002601863420000131
则同理降温速率
Figure BDA0002601863420000132
而对于温度均匀性评价指标本方法定义了一温度均匀性系数ξ,以96孔PCR基座为例,图3所示,点a为其基座上表面中心域点,点b为其基座上表面边缘端侧域点,温度均匀性偏差系数为
Figure BDA0002601863420000133
其中Ta1、Tb1指的是PCR基座升降温区间的上表面基座a点和b点温度值,即图2中的升降温时间t1和t2为区间;Ta2、Tb2则是指维持在给定温度进行反应的静态区间上表面中心域点和边缘域点温度值,其中静态区间指的是从一时刻温度达到稳态温度值且之后温度波动范围不超过5%到该温度区间反应结束为止,图2中t3、t4表示静态区间。λ则为动态过程与静态过程的权重系数,如果裸基座有限元模型仿真过程中PCR基座的温度存在较大稳态误差,则令λ<1,同理若发现升降温速率较慢则取λ>1,λ具体取值根据裸基座仿真中PCR基座温度性能动静态上存在不足的严重程度进行给定。Steady-state error ess = a, overshoot σ = b, heating rate v up = c, cooling rate v down = d, temperature uniformity coefficient ξ = f; as shown in Figure 2, it is a step curve of heating and cooling In the figure, T 1 and T 4 are the given target temperature values in the heating and cooling intervals, respectively, T 2 and T 5 are the steady-state temperature values in the heating and cooling intervals, and the steady-state error ess refers to the difference between the target temperature value and the steady-state temperature. The difference between the state temperature values, the steady-state error in the heating interval is essup =T 1 -T 2 , and the steady-state error in the cooling interval is essdown =T 5 -T 4 . The overshoot refers to the maximum degree to which the adjusted parameter dynamically deviates from the given value, in which T 3 and T 6 are the dynamic deviation from the maximum temperature value in the heating and cooling interval respectively, so the overshoot in the heating interval
Figure BDA0002601863420000121
The overshoot in the cooling range
Figure BDA0002601863420000122
The heating and cooling rate refers to the temperature change rate from the initial value to the first time when the given temperature value is reached, where t 1 is the heating time, t 2 is the cooling time, ΔT 1 and ΔT 2 are the temperature changes during the heating and cooling period, Since the initial temperature in this schematic diagram is 20, ΔT 1 =T 1 -20, ΔT 2 =T 4 -T 2 is the heating rate
Figure BDA0002601863420000131
Similarly, the cooling rate
Figure BDA0002601863420000132
For the evaluation index of temperature uniformity, this method defines a temperature uniformity coefficient ξ. Taking a 96-well PCR susceptor as an example, as shown in Figure 3, point a is the center point of the upper surface of the susceptor, and point b is the susceptor The upper surface edge end side domain point, the temperature uniformity deviation coefficient is
Figure BDA0002601863420000133
Among them, T a1 and T b1 refer to the temperature values of points a and b on the upper surface of the base of the PCR base in the heating and cooling interval, that is, the heating and cooling times t 1 and t 2 in Figure 2 are the intervals; T a2 and T b2 are It refers to the temperature value of the surface center domain point and edge domain point on the static interval that is maintained at a given temperature for the reaction. t 3 and t 4 in Fig. 2 represent the static region until the reaction in the temperature region is completed. λ is the weight coefficient of the dynamic process and the static process. If there is a large steady-state error in the temperature of the PCR base during the simulation of the bare base finite element model, let λ < 1. Similarly, if the heating and cooling rate is found to be slow, then Take λ>1, and the specific value of λ is given according to the severity of the dynamic and static deficiencies of the PCR susceptor temperature performance in the bare susceptor simulation.

而在有限元仿真中其约束条件如式(1):In the finite element simulation, the constraints are as in formula (1):

ess≤a、σ≤b、vup≥c、vdown≥d、ζ≤f (1)e ss ≤a, σ≤b, v up ≥c, v down ≥d, ζ≤f (1)

其中a、b、c、d、f均表示设计指标系数;根据现有PCR基座性能完成对指标系数的制定:0≤a≤0.5,0≤b≤10%,2℃/s≤vup≤4℃/s,1.5℃/s≤vdownn≤3℃/s,0.4≤ξ≤1;Among them, a, b, c, d, and f all represent the design index coefficient; according to the performance of the existing PCR base, the index coefficient is formulated: 0≤a≤0.5, 0≤b≤10%, 2℃/s≤v up ≤4℃/s, 1.5℃/s≤v downn ≤3℃/s, 0.4≤ξ≤1;

步骤S22:初始化待优化制造参数为变量V1、V2、V3…Vn,其中,V1代指基座制造材料类型、V2代指保温材料类型、V3代指保温材料厚度,V4、…、Vn代指包括基座尺寸,试管孔大小,表面是否开凿梅花孔对PCR基座可能有影响的参数;根据实际材料类型的选择来设定变量对应的步长;Step S22: Initialize the manufacturing parameters to be optimized as variables V 1 , V 2 , V 3 . . . V n , wherein V 1 refers to the type of base manufacturing material, V 2 refers to the type of thermal insulation material, and V 3 refers to the thickness of thermal insulation material, V 4 , .

根据实际参数选取范围如V1基座制造材料类型可在任意导热性能较好的金属中选取如(铝、铜),V2保温材料类型在隔热性能较好的材料中如(泡棉,聚乙烯,硅酸铝),V3保温材料厚度在符合实际厚度范围(0,100)[mm]完成对优化参数步长的设定;According to the actual parameter selection range, the material type of V1 base can be selected from any metal with good thermal conductivity, such as (aluminum, copper), and the type of V2 thermal insulation material can be selected from materials with good thermal insulation performance, such as (foam, polyethylene) , aluminum silicate), the thickness of V3 insulation material is in line with the actual thickness range (0,100) [mm] to complete the setting of the optimization parameter step size;

步骤S23:进行传感的实现及控制方法的选择,通过在PCR基座任一侧壁中点添加域点探针ppb1测量实时温度传感作为所采用控制算法的输入,控制方法则能够采用包括PID控制、模糊控制、内模控制或Smith预估控制智能控制算法作为系统控制方案;Step S23: Carry out the realization of sensing and the selection of the control method, by adding the domain point probe ppb1 to the midpoint of any side wall of the PCR base to measure the real-time temperature sensing as the input of the adopted control algorithm, and the control method can include: PID control, fuzzy control, internal model control or Smith predictive control intelligent control algorithm as the system control scheme;

步骤S24:根据实际制造成本制定优化性价比系数θ,初始化优化性价比系数θ,其表达式如式(2)根据制造成本定义变量V1、V2、V3…Vn的权重系数P1、P2、P3…PnStep S24: formulate the optimized cost-effectiveness coefficient θ according to the actual manufacturing cost, and initialize the optimized cost-effectiveness coefficient θ, whose expression is as in formula (2) to define the weighting coefficients P 1 , P of the variables V 1 , V 2 , V 3 . . . V n according to the manufacturing cost 2 , P3 ... Pn ;

θ=P1×V1+P2×V2+P3×V3+…+Pn×Vn (2)θ=P 1 ×V 1 +P 2 ×V 2 +P 3 ×V 3 +…+P n ×V n (2)

步骤S25:初始化停止条件及仿真搜索次数;设定停止条件如下:Step S25: Initialize stop conditions and simulation search times; set stop conditions as follows:

1)运行迭代次数达到最大迭代次数:n1>n2 1) The number of running iterations reaches the maximum number of iterations: n 1 >n 2

2)目标函数F下降梯度收敛:即Fk-Fk-1<T2) The objective function F descends the gradient convergence: that is, F k -F k-1 <T

其中,n1为此时制造参数优化数据寻优迭代次数、n2为根据实际优化过程中计算资源所制定的最大数据寻优迭代次数,可取500~10000。Fk表示k次迭代计算得到的目标值,T是设定的阈值常量,建议设为10-6Among them, n 1 is the number of optimization iterations of manufacturing parameter optimization data at this time, and n 2 is the maximum number of iterations of data optimization based on computing resources in the actual optimization process, which can be 500 to 10,000. F k represents the target value calculated by k iterations, and T is the set threshold constant, which is recommended to be set to 10 -6 .

如图5所示,在本实施例中,所述步骤S3的具体内容为:As shown in FIG. 5, in this embodiment, the specific content of step S3 is:

步骤S31:进行3D模型的设置:Step S31: Set the 3D model:

将所绘制的裸基座模型导入COMSOLMultiphysics其为C4,于COMSOLMultiphysics中绘制三个长方体C1、C2、C3;其中C1、C2、C3与从外部导入的裸基座C4的长宽高分别为(a1,b1,c1)、(a2,b2,c2)、(a3,b3,c3)、(a4,b4,c4);令C1、C2的中心点座标(x1,y1,z1)、(x2,y2,z2)与C4中心点座标(x4,y4,z4)一致,而C3中心点座标为(x4,,y4,z4+0.5c3+0.5c4),而其关系式如式(3)所示:Import the drawn bare pedestal model into COMSOL Multiphysics as C 4 , and draw three rectangular parallelepipeds C 1 , C 2 , C 3 in COMSOL Multiphysics; among them C 1 , C 2 , C 3 and the bare pedestal C 4 imported from outside The length, width and height are respectively (a 1 , b 1 , c 1 ), (a 2 , b 2 , c 2 ), (a 3 , b 3 , c 3 ), (a 4 , b 4 , c 4 ); Let the coordinates of the center point (x 1 , y 1 , z 1 ) and (x 2 , y 2 , z 2 ) of C 1 and C 2 agree with the coordinates of the center point of C 4 (x 4 , y 4 , z 4 ) , and the coordinates of the center point of C 3 are (x 4 , y 4 , z 4 +0.5c 3 +0.5c 4 ), and its relational expression is shown in formula (3):

a1≥a2=a4,b1≥b2=b4,c1=c2=c4,(a1-a2)=(b1-b2) (3)a 1 ≥a 2 =a 4 , b 1 ≥b 2 =b 4 , c 1 =c 2 =c 4 , (a 1 -a 2 )=(b 1 -b 2 ) (3)

其中(a3,b3,c3)根据选用热源尺寸进行设置,故2*(a1-a2)为保温材料的厚度;令C1和C2形成差集C5即为在基座四周包覆的保温材料并对C3、C4、C5构建联合体则形成一个裸基座四周包覆保温材料底部放置热源的PCR基座有限元几何模型;其中,所述C3表示热源,C4表示裸基座,C5表示保温材料;Among them (a 3 , b 3 , c 3 ) are set according to the size of the selected heat source, so 2*(a 1 -a 2 ) is the thickness of the thermal insulation material; let C 1 and C 2 form a difference set C 5 is the base The thermal insulation material covered around it and the combination of C 3 , C 4 , and C 5 are constructed to form a PCR base finite element geometric model with a heat source placed at the bottom of the bare base surrounded by the thermal insulation material; wherein, the C 3 represents the heat source. , C 4 represents the bare base, C 5 represents the thermal insulation material;

步骤S32:对PCR基座传热模型进行分析,在COMSOL Multiphy sics传热模块中选用能够实现PCR基座温度场特性的物理场进行有限元数值仿真:Step S32: Analyze the heat transfer model of the PCR base, and select a physical field that can realize the temperature field characteristics of the PCR base in the COMSOL Multiphysics heat transfer module to perform finite element numerical simulation:

由于PCR基座形状复杂且无内热源,故其导热问题只能用在笛卡尔坐标系中稳态、无内热源条件下导热微分方程进行描述,如式(4)所示:Due to the complex shape of the PCR base and no internal heat source, the thermal conductivity problem can only be described by the differential equation of thermal conductivity in the Cartesian coordinate system under the condition of steady state and no internal heat source, as shown in formula (4):

Figure BDA0002601863420000161
Figure BDA0002601863420000161

基座稳态热分析边界条件包括:基座底面的第一类边界条件、基座侧壁的对流换热第三类边界条件;由于基座底面与热源进行接触,故当温度升/降到恒定值时,基座底面与热源的接触面保持恒定温度,基座侧壁与空气存在自然对流换热,其边界条件如式(5)所示:The boundary conditions for steady-state thermal analysis of the base include: the first type of boundary conditions on the bottom of the base, and the third type of boundary conditions for convection heat transfer on the sidewall of the base; because the base bottom is in contact with the heat source, when the temperature rises/drops to When the value is constant, the contact surface between the bottom surface of the base and the heat source maintains a constant temperature, and there is natural convection heat exchange between the side wall of the base and the air. The boundary conditions are shown in formula (5):

Figure BDA0002601863420000162
Figure BDA0002601863420000162

其中,tw为基座温度,tf为周围空气温度,h为对流换热系数,λ0为热传导系数,n为基座侧壁法向方向;对于PCR基座温度控制是通过对其底部设置的热源发热量P以基座侧壁测点ppb1作为输入对热源发热功率P进行控制并将热量传递到PCR基座完成变温循环;通过对P CR基座温度场分析得出采用COMSOL Multiphysics中传热模块中的固体传热物理场用以完成有限元数值仿真;Among them, t w is the base temperature, t f is the ambient air temperature, h is the convective heat transfer coefficient, λ 0 is the thermal conductivity coefficient, and n is the normal direction of the base side wall; The heat source P of the set heat source takes the measurement point ppb1 on the side wall of the base as the input to control the heat power P of the heat source and transfers the heat to the PCR base to complete the temperature change cycle; The solid heat transfer physics in the heat transfer module is used to complete the finite element numerical simulation;

步骤S33:在固体传热物理场中完成对基座、热源、保温材料的材料类型及参数设置;Step S33: Complete the material type and parameter settings for the base, heat source, and thermal insulation material in the solid heat transfer physical field;

利用COMSOL Multiphysics中内置的材料库直接进行搜索或自行定义一个空材料,需要键入材料的恒压热容Cp[J/(kg·K)]、导热系数λ0[W/(m·K)]和密度ρ(kg/m3);Use the built-in material library in COMSOL Multiphysics to search directly or define an empty material by yourself, you need to enter the constant pressure heat capacity C p [J/(kg·K)], thermal conductivity λ 0 [W/(m·K) ] and density ρ (kg/m 3 );

步骤S34:在固体传热物理场中设置探针和热源热耗率设置:Step S34: Set the probe and heat source heat consumption rate settings in the solid heat transfer physics field:

在PCR基座任一侧壁布置温度传感器并在侧壁中心位置增加一域点探针ppb1,该域点探针布置位置如图3所示;Arrange a temperature sensor on any side wall of the PCR base and add a domain point probe ppb 1 at the center of the side wall, and the position of the domain point probe is shown in Figure 3;

根据所选用的控制算法(在本实例中采取的是PID控制算法)完成对热源发热功率P的控制以改变热源热耗率Q的大小实现三温区循环控制;热源热耗率Q表达式如式(6)所示,本实例中P的表达式如式(7)所示:According to the selected control algorithm (in this example, the PID control algorithm is adopted), the control of the heat source heating power P is completed to change the size of the heat source heat consumption rate Q to realize the three-temperature zone cycle control; the heat source heat consumption rate Q is expressed as As shown in formula (6), the expression of P in this example is as shown in formula (7):

Figure BDA0002601863420000171
Figure BDA0002601863420000171

Figure BDA0002601863420000172
Figure BDA0002601863420000172

其中,P为热源功率,V为热源体积,Tppb1为域点探针ppb1测得温度值,Ti为输入温度值;当选用热源不同时可根据其实际发热情况对公式(6)进行修改。Among them, P is the heat source power, V is the heat source volume, T ppb1 is the temperature value measured by the domain point probe ppb1, and T i is the input temperature value; when the selected heat source is different, formula (6) can be modified according to its actual heating condition .

步骤S35:在固体传热物理场中进行边界条件的设置:Step S35: Set the boundary conditions in the solid heat transfer physics field:

设定基座侧壁与空气所存在的自然对流换热,若是裸基座则基座侧壁与空气存在自然对流换热,无需如式(5)进行计算,在COMSOL Multiphysics热通量模块中选择外部自然对流换热,垂直壁,需键入壁高度L(m)、外部温度Text(K)、绝对压力PA(Pa)并将流体种类选择为空气;若是基座侧壁存在保温材料,则其侧壁与空气存在自然对流换热可忽略不计,故保温材料侧壁温度定义为室温T0即可;基座上表面由于实际PCR基座反应过程中会放置104℃左右的恒温热盖防止试剂的挥发,故上表面视为绝热;Set the natural convection heat exchange between the sidewall of the base and the air. If the base is bare, there is a natural convection heat transfer between the sidewall of the base and the air. There is no need to perform the calculation as in Equation (5). In the COMSOL Multiphysics Heat Flux Module Select external natural convection heat transfer, vertical wall, need to enter wall height L (m), external temperature T ext (K), absolute pressure P A (Pa) and select the fluid type as air; if there is thermal insulation material on the side wall of the base , the natural convection heat exchange between the side wall and the air can be ignored, so the temperature of the side wall of the thermal insulation material can be defined as room temperature T 0 ; the upper surface of the base will be placed with a constant temperature of about 104°C during the actual PCR base reaction process. The cover prevents the volatilization of the reagent, so the upper surface is regarded as adiabatic;

对于网格的划分:使用对几何适应性最好的自由四面体进行网格的划分;由于PCR基座中在试管孔部分为形状较为复杂的环节,为节省计算资源先创建一个自由四面体网格进行全局绘制,再通过细化功能对试管孔面及其连接处进行细化,完成网格绘制;For mesh division: use the free tetrahedron with the best geometric adaptability for mesh division; since the test tube hole in the PCR base is a complex part of the shape, in order to save computing resources, first create a free tetrahedron mesh The grid is drawn globally, and then the hole surface of the test tube and its connections are refined through the refinement function to complete the grid drawing;

步骤S36:在固体传热物理场中进行求解器的配置:选择瞬态求解器,对求解器相对容差设为0.01;时间步进方法选为广义α,采用步长选为中级,代数变量设置中一致初始化选用向后欧拉法,初始步长分数为0.001.完成求解器配置,并保存文件,格式另存为.m格式为后续调用with Matlab接口做准备;Step S36: Configure the solver in the solid heat transfer physics field: select the transient solver, set the relative tolerance to the solver as 0.01; select the time step method as generalized α, select the step size as the intermediate level, and select the algebraic variable In the settings, the backward Euler method is selected for consistent initialization, and the initial step fraction is 0.001. Complete the solver configuration, and save the file in .m format to prepare for subsequent calls to the with Matlab interface;

步骤S37:在固体传热物理场中进行有限元数值仿真:根据所设置的有限元模型进行数值仿真,得到PCR基座热交换过程动态热场分布,并通过计算域点探针ppb1温度值曲线稳态误差ess、超调量σ升降、温速率vup、vdown,并根据式(2)计算优化性价比系数ξ,将所有结果保存为输出O1k{V1、V2、V3…Vn、essk、σk、vupk、vdownk、ξk、θk}{0<k≤n2︱k∈Z}。Step S37: carry out finite element numerical simulation in the solid heat transfer physical field: carry out numerical simulation according to the set finite element model, obtain the dynamic thermal field distribution of the heat exchange process of the PCR base, and calculate the temperature value curve of the domain point probe ppb1 by calculating Steady-state error ess , overshoot σ rise and fall, temperature rate v up , v down , and calculate the optimized cost performance coefficient ξ according to formula (2), and save all the results as output O 1k {V 1 , V 2 , V 3 … V n , essk , σ k , v upk , v downk , ξ k , θ k }{0<k≤n 2 ︱k∈Z}.

在本实施例中,所述步骤S4的具体内容为:In this embodiment, the specific content of the step S4 is:

利用COMSOL Multiphysics生成步骤S35中设置好的有限元模型的.m文件使用with MATLAB接口对.m文件进行式(1)为约束条件,S25中(1)、(2)为停止条件,搜索次数为n2T是设定的阈值常量的定义;根据设定的搜索策略实现每次在(2)中变量V1、V2、V3的选定下步骤S37中计算结果O1k{V1、V2、V3…Vn、essk、σk、vupk、vdownk、ξk、θk}{0<k≤n2︱k∈Z}输出;判定是否满足停止迭代条件(1)、(2),若是则退出循环进入步骤S5;否则根据式(1)约束,更新新的仿真参数输入步骤S3重新进行有限元数值仿真。Use COMSOL Multiphysics to generate the .m file of the finite element model set in step S35. Use the with MATLAB interface to perform the .m file on the .m file. Formula (1) is the constraint condition, (1) and (2) in S25 are the stopping conditions, and the number of searches is n 2 T is the definition of the set threshold constant; according to the set search strategy, the calculation result O 1k { V 1 , V 1 , V 2 , V 3 . . . V n , essk , σ k , v upk , v downk , ξ k , θ k }{0<k≤n 2 ︱k∈Z} output; determine whether the stop iteration condition (1) is satisfied , (2), if it is, exit the loop and go to step S5; otherwise, according to the constraint of formula (1), update the new simulation parameters and input step S3 to perform the finite element numerical simulation again.

在本实施例中,所述设定的搜索策略包括网格搜索、粒子群算法、模拟退火或蚁群算法。(本方法及流程图1以遗传算法进行说明)In this embodiment, the set search strategy includes grid search, particle swarm algorithm, simulated annealing or ant colony algorithm. (This method and flowchart 1 are explained by genetic algorithm)

在本实施例中,所述步骤S6的具体内容为:判断是否满足停止条件(1)、(2),若满足则停止计算,输出优化集合O{V1、V2、V3…Vn、ess、σ、vup、vdown、ξ、θ},并进行优化结果处理,完成PCR基座制造参数优化;否则更新变量返回步骤S3。In this embodiment, the specific content of the step S6 is: judging whether the stopping conditions (1) and (2) are met, if so, stop the calculation, and output the optimized set O{V 1 , V 2 , V 3 . . . V n , ess , σ, v up , v down , ξ, θ}, and process the optimization results to complete the optimization of the manufacturing parameters of the PCR base; otherwise, update the variables and return to step S3.

在本实施例中,所述优化结果处理的具体内容为:In this embodiment, the specific content of the optimization result processing is:

根据计算结果,将所有符合式(1)的输出值O1k{V1、V2、V3…Vn、essk、σk、vupk、vdownk、ξk、θk}{0<k≤n2︱k∈Z}输入集合O,根据θk{0<k≤n2︱k∈Z}从大到小的方式进行集合的重新排序,输出集合O提交给用户;根据用户定制的优化原则,在集合O中根据实际需求即当希望性价比更高则根据其性价比系数θ作为选择主要依据,若希望有更好的温度均匀性则以均匀性系数ξ作为选择的主要依据,同理希望有更快的升降温速率则考虑vupk、vdownk,希望有更好的温度精度则考虑essk、σk进一步筛选获得最优的制造参数结果,完成优化。According to the calculation result, all output values O 1k {V 1 , V 2 , V 3 . . . V n , essk , σ k , v upk , v downk , ξ k , θ k }{0< k≤n 2 ︱k∈Z} input set O, reorder the set from large to small according to θ k {0<k≤n 2 ︱k∈Z}, and submit the output set O to the user; customized according to the user According to the optimization principle, in the set O, according to the actual demand, that is, when the cost performance is expected to be higher, the cost performance coefficient θ is used as the main basis for selection; if better temperature uniformity is desired, the uniformity coefficient ξ is used as the main basis for selection. Ideally, if a faster heating and cooling rate is desired, v upk and v downk should be considered. If better temperature accuracy is desired, essk and σ k should be considered for further screening to obtain the optimal manufacturing parameter results and complete the optimization.

较佳的,本实施例通过常用有限元软件COMSOL Multiphysics及其withMATLAB接口,构建数值仿真方法,用瞬态分析的方法给出了PCR基座有限元模型实际温度控制过程,并以此结果进行制造参数优化设计,以保证PCR基座在实际热循环过程中能够取得最优的动态和静态性能。本实施例能够在满足PCR基座温度性能指标下,获得的优化制造参数,如保温材料最优尺寸等可用于指导实际基座加工,保证其在热循环过程中保持快速温度响应前提下具有良好的热均匀性。为便于理解本发明方法,我们以96孔PCR基座制造参数优化为例使用COMSOL Multiphysics及其withMATLAB接口进行数值求解得到满足设计指标要求的基座包围参数。发明能够为新型PCR基座的研发大幅节约了时间和物质上的成本。Preferably, in this embodiment, a numerical simulation method is constructed through the commonly used finite element software COMSOL Multiphysics and its withMATLAB interface, and the actual temperature control process of the finite element model of the PCR base is given by the method of transient analysis, and manufacturing is carried out based on the results. The parameters are optimized to ensure the optimal dynamic and static performance of the PCR base during the actual thermal cycling process. The optimized manufacturing parameters obtained in this embodiment, such as the optimal size of the thermal insulation material, can be used to guide the actual susceptor processing under the condition that the temperature performance index of the PCR susceptor is satisfied, so as to ensure that it has good performance under the premise of maintaining a fast temperature response during the thermal cycle. thermal uniformity. In order to facilitate the understanding of the method of the present invention, we take the optimization of the manufacturing parameters of the 96-well PCR pedestal as an example, and use COMSOL Multiphysics and its withMATLAB interface to numerically solve the pedestal surrounding parameters that meet the requirements of the design indicators. The invention can greatly save time and material cost for the research and development of new PCR bases.

以96孔PCR基座为例进行优化,其3D模型设计工程图如图6所示。Taking the 96-well PCR base as an example for optimization, the 3D model design engineering drawing is shown in Figure 6.

⑵初始化仿真条件,令其约束条件(1)式中a=0.2,b=5%,vup=2.5℃/s,vdownn=2℃/s,ξ=0.8,λ=1.2;令变量V1、V2、V3为(铝,铜),(硅酸铝棉,聚乙烯泡棉),(0,100,1);采用热源为碳纤维加热片,控制算法为PID控制算法;令其(2)式中P1、P2、P3分别为0.5、2、3,令停止条件中n2为1000,T为10-6(2) Initialize the simulation conditions and make the constraints (1) where a = 0.2, b = 5%, v up = 2.5 °C/s, v downn = 2 °C/s, ξ = 0.8, λ = 1.2; let the variable V 1. V 2 and V 3 are (aluminum, copper), (aluminum silicate cotton, polyethylene foam), (0,100,1); the heat source is carbon fiber heating plate, and the control algorithm is PID control algorithm; let it (2 ) where P 1 , P 2 , and P 3 are 0.5, 2, and 3, respectively, and n 2 is 1000 and T is 10 -6 in the stopping condition.

⑶完成有限元初始化条件的设置及数值仿真。按步骤S2所示方法完成有限元初始化条件设置,令模型的初始环境温度为20℃,其中P CR基座有限元几何模型如图7所示,所导入材料参数如表1所示,域点探针ppb1位置如图3所示,网格划分示例图如图8所示,热源功率表达式P如式(7)所示,其中Tppb1为域点探针ppb1测得温度值,Ti为输入温度值,在PCR基座模型中三温区分别为94℃-55℃-72℃,因此CO MSOL Multiphysics中需分别定义P94、P55、P72,在本实施例中规定0-90s为94℃温区,90-180s为55℃温区,180-240s为72℃温区,在固体传热中热源热耗率Q的计算中功率P输入表达式如式(8)所示,当选用热源进行变化时根据其实际发热情况对公式进行修改。其中由于无法直接定义

Figure BDA0002601863420000211
需先将其定义为代数I在式(7)中进行指代,然后再选用COMSOL Multiphysics数学物理场中全局微分和常微分方程进行I表达式的定义。(3) Complete the setting of finite element initialization conditions and numerical simulation. The finite element initialization conditions are set according to the method shown in step S2, and the initial ambient temperature of the model is set to 20 °C. The finite element geometric model of the PCR base is shown in Figure 7, and the imported material parameters are shown in Table 1. The domain point The position of the probe ppb1 is shown in Figure 3, the grid division example is shown in Figure 8, and the heat source power expression P is shown in formula (7), where T ppb1 is the temperature value measured by the domain point probe ppb1, and T i In order to input the temperature value, in the PCR base model, the three temperature zones are 94°C-55°C-72°C, respectively, so P 94 , P 55 , and P 72 need to be defined respectively in CO MSOL Multiphysics. In this example, 0- 90s is the temperature zone of 94°C, 90-180s is the temperature zone of 55°C, and 180-240s is the temperature zone of 72°C. In the calculation of the heat source heat consumption rate Q in solid heat transfer, the input expression of power P is shown in formula (8). , when the heat source is selected to change, the formula is modified according to its actual heating situation. which cannot be directly defined
Figure BDA0002601863420000211
It needs to be defined as algebra I and referred to in equation (7), and then the global differential and ordinary differential equations in the mathematical physics field of COMSOL Multiphysics are used to define the expression of I.

Figure BDA0002601863420000212
Figure BDA0002601863420000212

P=P94*(t>=0&t<=90)+P55*(t>90&t<180)+P72*(t>=180&t<=240) (8)P=P 94 *(t>=0&t<=90)+P 55 *(t>90&t<180)+P 72 *(t>=180&t<=240) (8)

表1导入材料参数表Table 1 Import material parameter table

Figure BDA0002601863420000213
Figure BDA0002601863420000213

⑷完成优化方法设置。生成模型.m文件,设定好初始条件,停止条件后本次使用粒子群算法为例进行搜索,将变量V1、V2、V3设为三个粒子,当结果O1k(essk、σk、vupk、vdownk、ξk、θk){0<k≤n2︱k∈Z}满足约束条件式(1)时则保存该优化结果至集合O。本方法中,停止的条件为迭代次数超过n2或目标函数F下降梯度收敛。完成迭代后将数据集O输出给用户。优化方法流程图如图9所示。优化后得到一组数据组为(铝,硅酸铝棉,40mm)其PCR基座三温区热场图如图10-12所示,而其基座测点即图3中ppb1点位置温度动态曲线如图13所示,可以根据步骤S2中方法算得该基座稳态误差ess94=0.117℃、ess55=0.130℃、ess72=0.108℃,超调量σ94=3.8%、σ55=4.5%、σ72=4.2%,升降温速率分别为v94=2.96℃/s、v55=2.13℃/s、v94=2.64℃/s,ξ=0.74,符合提前指定指标,故该优化数据组符合要求。⑷Complete the optimization method setting. Generate the model .m file , set the initial conditions, and use the particle swarm algorithm as an example to search this time after the stopping conditions . When σ k , v upk , v downk , ξ k , θ k ){0<k≤n 2 ︱k∈Z} satisfies the constraint condition (1), save the optimization result to the set O. In this method, the stopping condition is that the number of iterations exceeds n 2 or the gradient of the objective function F descends to converge. After the iteration is completed, the dataset O is output to the user. The flow chart of the optimization method is shown in Figure 9. After optimization, a data set is obtained (aluminum, aluminum silicate wool, 40mm), and the thermal field map of the three-temperature zone of the PCR base is shown in Figure 10-12, and the measurement point of the base is the temperature at the ppb1 point in Figure 3. The dynamic curve is shown in Figure 13. According to the method in step S2, the steady-state error of the base can be calculated as ess94 = 0.117°C, ess55 = 0.130°C, ess72 = 0.108°C, overshoot σ 94 = 3.8%, σ 55 =4.5%, σ 72 =4.2%, the heating and cooling rates are v 94 =2.96°C/s, v 55 =2.13°C/s, v 94 =2.64°C/s, ξ=0.74, which are in line with the pre-specified indicators, so the The optimized data set meets the requirements.

⑸优化结果处理⑸Optimize result processing

将数据集O按制造优化权重系数θ从大到小进行排序,选取θ最大的作为最优化结果进行处理,并保存优化数据集O方便后续进行实验验证。完成制造参数优化。The data set O is sorted according to the manufacturing optimization weight coefficient θ from large to small, and the one with the largest θ is selected as the optimization result for processing, and the optimized data set O is saved for subsequent experimental verification. Complete the optimization of manufacturing parameters.

较佳的,本实施例通过利用有限元瞬态分析方法可以监测整个循环周期PCR基座热场,极大的贴合实际情况的同时也可以根据所制定基座制造参数优化指标并完成优化得到基座制造参数优化数据。提高PCR基座温度动静态性能。满足工作需求,大幅降低新型PCR仪研发成本。通过将传感和控制加入有限元数值仿真中,实现更加贴近真实温度控制的动态仿真。Preferably, by using the finite element transient analysis method, the thermal field of the PCR pedestal can be monitored in this embodiment, which greatly fits the actual situation, and can also optimize the index according to the established pedestal manufacturing parameters and complete the optimization. Pedestal manufacturing parameter optimization data. Improve the dynamic and static performance of PCR base temperature. Meet work needs and greatly reduce the cost of research and development of new PCR instruments. By adding sensing and control to the finite element numerical simulation, a dynamic simulation closer to the real temperature control is realized.

以上所述仅为本发明的较佳实施例,凡依本发明申请专利范围所做的均等变化与修饰,皆应属本发明的涵盖范围。The above descriptions are only preferred embodiments of the present invention, and all equivalent changes and modifications made according to the scope of the patent application of the present invention shall fall within the scope of the present invention.

Claims (7)

1.一种基于有限元模型数值仿真的PCR基座制造参数优化方法,其特征在于:包括以下步骤:1. a PCR base manufacturing parameter optimization method based on finite element model numerical simulation, is characterized in that: comprise the following steps: 步骤S1:进行基座3D模型设计:根据实际设计所需要孔数,大小进行PCR基座的3D模型绘制;Step S1: Design the 3D model of the base: draw the 3D model of the PCR base according to the number and size of holes required for the actual design; 步骤S2:初始化仿真条件;Step S2: Initialize simulation conditions; 步骤S3:进行有限元模型初始化条件设置及仿真;Step S3: setting and simulating the initialization conditions of the finite element model; 步骤S4:进行优化方法设置,并判断是否符合约束条件,若符合则继续执行步骤S5,否则更新变量并返回步骤S3;Step S4: set the optimization method, and judge whether the constraint conditions are met, if so, continue to execute step S5, otherwise update the variables and return to step S3; 步骤S5:保存结果O1k{0<k≤n2︱k∈Z}至优化集O;Step S5: save the result O 1k {0<k≤n 2 ︱k∈Z} to the optimization set O; 步骤S6:判断是否符合停止条件式(1)、式(2),若符合则输出优化集O,并进行优化结果处理,完成PCR基座制造参数优化,否则更新变量并返回步骤S3。Step S6: Determine whether the stop condition formula (1) and formula (2) are met, if so, output the optimization set O, and process the optimization result to complete the optimization of the manufacturing parameters of the PCR base, otherwise update the variables and return to step S3. 2.根据权利要求1所述的一种基于有限元模型数值仿真的PCR基座制造参数优化方法,其特征在于:所述步骤S2具体包括以下步骤:2. a kind of PCR base manufacturing parameter optimization method based on finite element model numerical simulation according to claim 1, is characterized in that: described step S2 specifically comprises the following steps: 步骤S21:初始化PCR基座静态和动态指标作为约束条件,稳态误差为ess,超调量为σ,升温速率为vup,降温速率为vdown,温度均匀性系数为ξ;Step S21: initialize the static and dynamic indicators of the PCR base as constraints, the steady-state error is ess , the overshoot is σ, the heating rate is v up , the cooling rate is v down , and the temperature uniformity coefficient is ξ; 稳态误差ess=a,超调量σ=b,升温速率vup=c,降温速率vdown=d,温度均匀性系数ξ=f;而在有限元仿真中其约束条件如式(1):Steady-state error ess = a, overshoot σ = b, heating rate v up = c, cooling rate v down = d, temperature uniformity coefficient ξ = f; and the constraints in the finite element simulation are as follows (1 ): ess≤a、σ≤b、vup≥c、vdown≥d、ζ≤f (1)e ss ≤a, σ≤b, v up ≥c, v down ≥d, ζ≤f (1) 其中a、b、c、d、f均表示设计指标系数;根据现有PCR基座性能完成对指标系数的制定:0≤a≤0.5,0≤b≤10%,2℃/s≤vup≤4℃/s,1.5℃/s≤vdownn≤3℃/s,0.4≤ξ≤1;Among them, a, b, c, d, and f all represent the design index coefficient; according to the performance of the existing PCR base, the index coefficient is formulated: 0≤a≤0.5, 0≤b≤10%, 2℃/s≤v up ≤4℃/s, 1.5℃/s≤v downn ≤3℃/s, 0.4≤ξ≤1; 步骤S22:初始化待优化制造参数为变量V1、V2、V3…Vn,其中,V1代指基座制造材料类型、V2代指保温材料类型、V3代指保温材料厚度,V4、…、Vn代指包括基座尺寸,试管孔大小,表面是否开凿梅花孔对PCR基座可能有影响的参数;根据实际材料类型的选择来设定变量对应的步长;Step S22: Initialize the manufacturing parameters to be optimized as variables V 1 , V 2 , V 3 . . . V n , wherein V 1 refers to the type of base manufacturing material, V 2 refers to the type of thermal insulation material, and V 3 refers to the thickness of thermal insulation material, V 4 , ..., Vn refer to the parameters including the size of the base, the size of the test tube hole, and whether the surface of the plum blossom hole may have an impact on the PCR base; the step size corresponding to the variable is set according to the selection of the actual material type; 步骤S23:进行传感的实现及控制方法的选择,通过在PCR基座侧壁添加域点探针ppb1测量实时温度传感作为所采用控制算法的输入,控制方法则能够采用包括PID控制、模糊控制、内模控制或Smith预估控制智能控制算法作为系统控制方案;Step S23: Carry out the realization of the sensing and the selection of the control method, by adding the domain point probe ppb1 on the side wall of the PCR base to measure the real-time temperature sensing as the input of the adopted control algorithm, and the control method can include PID control, fuzzy Control, internal model control or Smith predictive control intelligent control algorithm as the system control scheme; 步骤S24:根据实际制造成本制定优化性价比系数θ,初始化优化性价比系数θ,其表达式如式(2)根据制造成本定义变量V1、V2、V3、…、Vn的权重系数P1、P2、P3、…、PnStep S24 : formulate the optimized cost-effectiveness coefficient θ according to the actual manufacturing cost, and initialize the optimized cost-effectiveness coefficient θ, whose expression is as in formula (2) according to the manufacturing cost to define the weight coefficient P1 of the variables V 1 , V 2 , V 3 , . . . , V n , P 2 , P 3 , ..., P n ; θ=P1×V1+P2×V2+P3×V3+…+Pn×Vn (2)θ=P 1 ×V 1 +P 2 ×V 2 +P 3 ×V 3 +…+P n ×V n (2) 步骤S25:初始化停止条件及仿真搜索次数;设定停止条件如下:Step S25: Initialize stop conditions and simulation search times; set stop conditions as follows: 运行迭代次数达到最大迭代次数:n1>n2 The number of running iterations reaches the maximum number of iterations: n 1 >n 2 目标函数F下降梯度收敛:即Fk-Fk-1<TThe objective function F descends the gradient convergence: that is, F k -F k-1 <T 其中,n1为此时制造参数优化数据寻优迭代次数、n2为根据实际优化过程中计算资源所制定的最大数据寻优迭代次数,取500~10000;Fk表示k次迭代计算得到的目标值,T是设定的阈值常量,设为10-6Among them, n 1 is the number of optimization iterations of the manufacturing parameter optimization data at this time, and n 2 is the maximum number of data optimization iterations based on the computing resources in the actual optimization process, taking 500 to 10,000; F k represents the calculated value obtained by k iterations The target value, T is the set threshold constant, set to 10 -6 . 3.根据权利要求2所述的一种基于有限元模型数值仿真的PCR基座制造参数优化方法,其特征在于:所述步骤S3的具体内容为:3. a kind of PCR base manufacturing parameter optimization method based on finite element model numerical simulation according to claim 2 is characterized in that: the concrete content of described step S3 is: 步骤S31:进行3D模型的设置:Step S31: Set the 3D model: 将所绘制的裸基座模型导入COMSOL Multiphysics其为C4,于COMSOL Multiphysics中绘制三个长方体C1、C2、C3;其中C1、C2、C3与从外部导入的裸基座C4的长宽高分别为(a1,b1,c1)、(a2,b2,c2)、(a3,b3,c3)、(a4,b4,c4);令C1、C2的中心点座标(x1,y1,z1)、(x2,y2,z2)与C4中心点座标(x4,y4,z4)一致,而C3中心点座标为(x4,,y4,z4+0.5c3+0.5c4),而其关系式如式(3)所示:Import the drawn bare pedestal model into COMSOL Multiphysics, which is C 4 , and draw three cuboids C 1 , C 2 , C 3 in COMSOL Multiphysics; among them C 1 , C 2 , C 3 and the bare pedestal imported from outside The length, width and height of C 4 are respectively (a 1 , b 1 , c 1 ), (a 2 , b 2 , c 2 ), (a 3 , b 3 , c 3 ), (a 4 , b 4 , c 4 ) ); let the coordinates of the center point of C 1 and C 2 (x 1 , y 1 , z 1 ), (x 2 , y 2 , z 2 ) and the coordinates of the center point of C 4 (x 4 , y 4 , z 4 ) ) is consistent, and the coordinates of the center point of C 3 are (x 4 , y 4 , z 4 +0.5c 3 +0.5c 4 ), and its relational formula is shown in formula (3): a1≥a2=a4,b1≥b2=b4,c1=c2=c4,(a1-a2)=(b1-b2) (3)a 1 ≥a 2 =a 4 , b 1 ≥b 2 =b 4 , c 1 =c 2 =c 4 , (a 1 -a 2 )=(b 1 -b 2 ) (3) 其中(a3,b3,c3)根据选用热源尺寸进行设置,故2*(a1-a2)为保温材料的厚度;令C1和C2形成差集C5即为在基座四周包覆的保温材料并对C3、C4、C5构建联合体则形成一个裸基座四周包覆保温材料底部放置热源的PCR基座有限元几何模型;其中,所述C3表示热源,C4表示裸基座,C5表示保温材料;Among them (a 3 , b 3 , c 3 ) are set according to the size of the selected heat source, so 2*(a 1 -a 2 ) is the thickness of the thermal insulation material; let C 1 and C 2 form a difference set C 5 is the base The thermal insulation material covered around it and the combination of C 3 , C 4 , and C 5 are constructed to form a PCR base finite element geometric model with a heat source placed at the bottom of the bare base surrounded by the thermal insulation material; wherein, the C 3 represents the heat source. , C 4 represents the bare base, C 5 represents the thermal insulation material; 步骤S32:对PCR基座传热模型进行分析,在COMSOL Multiphy sics传热模块中选用能够实现PCR基座温度场特性的物理场进行有限元数值仿真:Step S32: Analyze the heat transfer model of the PCR base, and select a physical field that can realize the temperature field characteristics of the PCR base in the COMSOL Multiphysics heat transfer module to perform finite element numerical simulation: 由于PCR基座形状复杂且无内热源,故其导热问题用在笛卡尔坐标系中稳态、无内热源条件下导热微分方程进行描述,如式(4)所示:Due to the complex shape of the PCR base and no internal heat source, its thermal conductivity problem is described by a differential equation of thermal conductivity in the Cartesian coordinate system under the condition of steady state and no internal heat source, as shown in formula (4):
Figure FDA0002601863410000041
Figure FDA0002601863410000041
基座稳态热分析边界条件包括:基座底面的第一类边界条件、基座侧壁的对流换热第三类边界条件;由于基座底面与热源进行接触,故当温度升/降到恒定值时,基座底面与热源的接触面保持恒定温度,基座侧壁与空气存在自然对流换热,其边界条件如式(5)所示:The boundary conditions for steady-state thermal analysis of the base include: the first type of boundary conditions on the bottom of the base, and the third type of boundary conditions for convection heat transfer on the sidewall of the base; because the base bottom is in contact with the heat source, when the temperature rises/drops to When the value is constant, the contact surface between the bottom surface of the base and the heat source maintains a constant temperature, and there is natural convection heat exchange between the side wall of the base and the air. The boundary conditions are shown in formula (5):
Figure FDA0002601863410000042
Figure FDA0002601863410000042
其中,tw为基座温度,tf为周围空气温度,h为对流换热系数,λ0为热传导系数,n为基座侧壁法向方向;对于PCR基座温度控制是通过对其底部设置的热源发热量P以基座侧壁测点ppb1作为输入对热源发热功率P进行控制并将热量传递到PCR基座完成变温循环;通过对PCR基座温度场分析得出采用COMSOL Multiphysics中传热模块中的固体传热物理场用以完成有限元数值仿真;Among them, t w is the base temperature, t f is the ambient air temperature, h is the convective heat transfer coefficient, λ 0 is the thermal conductivity coefficient, and n is the normal direction of the base side wall; The heat source P of the set heat source takes the measuring point ppb1 on the side wall of the base as the input to control the heat power P of the heat source and transfers the heat to the PCR base to complete the temperature change cycle; The solid heat transfer physics in the Thermal Module is used to complete finite element numerical simulations; 步骤S33:在固体传热物理场中完成对基座、热源、保温材料的材料类型及参数设置;Step S33: Complete the material type and parameter settings for the base, heat source, and thermal insulation material in the solid heat transfer physical field; 利用COMSOL Multiphysics中内置的材料库直接进行搜索或自行定义一个空材料,需要键入材料的恒压热容Cp[J/(kg·K)]、导热系数λ0[W/(m·K)]和密度ρ(kg/m3);Use the built-in material library in COMSOL Multiphysics to search directly or define an empty material by yourself, you need to enter the constant pressure heat capacity C p [J/(kg·K)], thermal conductivity λ 0 [W/(m·K) ] and density ρ (kg/m 3 ); 步骤S34:在固体传热物理场中设置探针和热源热耗率设置:Step S34: Set the probe and heat source heat consumption rate settings in the solid heat transfer physics field: 在PCR基座任一侧壁布置温度传感器并在侧壁中心位置增加一域点探针ppb1;根据所选用的控制算法包括备选的PID控制、模糊控制、内模控制或Smith预估控制智能控制算法完成对热源发热功率P的控制以改变热源热耗率Q的大小实现三温区循环控制;热源热耗率Q表达式如式(6)所示:Arrange a temperature sensor on either side wall of the PCR base and add a domain point probe ppb 1 at the center of the side wall; according to the selected control algorithm, it includes alternative PID control, fuzzy control, internal model control or Smith prediction control The intelligent control algorithm completes the control of the heat source heating power P to change the size of the heat source heat consumption rate Q to realize the three-temperature zone cycle control; the heat source heat consumption rate Q expression is shown in formula (6):
Figure FDA0002601863410000051
Figure FDA0002601863410000051
其中,P为热源功率,V为热源体积;Among them, P is the heat source power, V is the heat source volume; 步骤S35:在固体传热物理场中进行边界条件的设置:Step S35: Set the boundary conditions in the solid heat transfer physics field: 设定基座侧壁与空气所存在的自然对流换热,若是裸基座则基座侧壁与空气存在自然对流换热,无需如式(5)进行计算,在COMSOL Multiphysics热通量模块中选择外部自然对流换热,垂直壁,需键入壁高度L(m)、外部温度Text(K)、绝对压力PA(Pa)并将流体种类选择为空气;若是基座侧壁存在保温材料,则其侧壁与空气存在自然对流换热可忽略不计,故保温材料侧壁温度定义为室温T0即可;基座上表面由于实际PCR基座反应过程中会放置104℃左右的恒温热盖防止试剂的挥发,故上表面视为绝热;Set the natural convection heat exchange between the side wall of the base and the air. If the base is bare, there is natural convection heat exchange between the side wall of the base and the air. There is no need to perform the calculation as in Equation (5). In the heat flux module of COMSOL Multiphysics Select external natural convection heat transfer, vertical wall, need to enter wall height L (m), external temperature T ext (K), absolute pressure P A (Pa) and select the fluid type as air; if there is thermal insulation material on the side wall of the base , the natural convection heat exchange between the sidewall and the air can be ignored, so the temperature of the sidewall of the thermal insulation material can be defined as room temperature T The cover prevents the volatilization of the reagent, so the upper surface is regarded as adiabatic; 对于网格的划分:使用对几何适应性最好的自由四面体进行网格的划分;由于PCR基座中在试管孔部分为形状较为复杂的环节,为节省计算资源先创建一个自由四面体网格进行全局绘制,再通过细化功能对试管孔面及其连接处进行细化,完成网格绘制;For mesh division: use the free tetrahedron with the best geometric adaptability for mesh division; since the test tube hole in the PCR base is a complex part of the shape, in order to save computing resources, first create a free tetrahedron mesh The grid is drawn globally, and then the hole surface of the test tube and its connections are refined through the refinement function to complete the grid drawing; 步骤S36:在固体传热物理场中进行求解器的配置:选择瞬态求解器,对求解器相对容差设为0.01;时间步进方法选为广义α,采用步长选为中级,代数变量设置中一致初始化选用向后欧拉法,初始步长分数为0.001.完成求解器配置,并保存文件,格式另存为.m格式为后续调用with Matlab接口做准备;Step S36: Configure the solver in the solid heat transfer physics field: select the transient solver, set the relative tolerance to the solver as 0.01; select the time step method as generalized α, select the step size as the intermediate level, and select the algebraic variable In the settings, the backward Euler method is selected for consistent initialization, and the initial step fraction is 0.001. Complete the solver configuration, and save the file in .m format to prepare for subsequent calls to the with Matlab interface; 步骤S37:在固体传热物理场中进行有限元数值仿真:根据所设置的有限元模型进行数值仿真,得到PCR基座热交换过程动态热场分布,并通过计算域点探针ppb1温度值曲线稳态误差ess,超调量σ,升、降温速率vup、vdown;并根据式(2)计算优化性价比系数ξ,将所有结果保存为输出O1k{V1、V2、V3、…、Vn、essk、σk、vupk、vdownk、ξk、θk}{0<k≤n2︱k∈Z}。Step S37: carry out finite element numerical simulation in the solid heat transfer physical field: carry out numerical simulation according to the set finite element model, obtain the dynamic thermal field distribution of the heat exchange process of the PCR base, and calculate the temperature value curve of the domain point probe ppb1 by calculating Steady-state error ess , overshoot σ, heating and cooling rates v up , v down ; calculate the optimized cost-effectiveness coefficient ξ according to formula (2), and save all the results as output O 1k {V 1 , V 2 , V 3 , ... , V n , essk , σ k , v upk , v downk , ξ k , θ k }{0<k≤n 2 ︱k∈Z}.
4.根据权利要求3所述的一种基于有限元模型数值仿真的PCR基座制造参数优化方法,其特征在于:所述步骤S4的具体内容为:4. a kind of PCR base manufacturing parameter optimization method based on finite element model numerical simulation according to claim 3 is characterized in that: the concrete content of described step S4 is: 利用COMSOL Multiphysics生成步骤S35中设置好的有限元模型的.m文件使用withMATLAB接口对.m文件进行式(1)为约束条件,S25中(1)、(2)为停止条件,搜索次数为n2,T是设定的阈值常量的定义;根据设定的搜索策略实现每次在(2)中变量V1、V2、V3的选定下步骤S37中计算结果O1k{V1、V2、V3、…、Vn、essk、σk、vupk、vdownk、ξk、θk}{0<k≤n2︱k∈Z}输出;判定是否满足停止迭代条件(1)、(2),若是则退出循环进入步骤S5;否则根据式(1)约束,更新新的仿真参数输入步骤S3重新进行有限元数值仿真。Use COMSOL Multiphysics to generate the .m file of the finite element model set in step S35, and use the withMATLAB interface to execute the .m file on the .m file. Formula (1) is the constraint condition, (1) and (2) in S25 are the stopping conditions, and the number of searches is n 2 , T is the definition of the set threshold constant ; according to the set search strategy, the calculation result O 1k { V 1 , V 2 , V 3 , ..., V n , essk , σ k , v upk , v downk , ξ k , θ k }{0<k≤n 2 ︱k∈Z} output; determine whether the stop iteration condition ( 1), (2), if so, exit the loop and go to step S5; otherwise, according to the constraints of formula (1), update the new simulation parameters and input step S3 to perform the finite element numerical simulation again. 5.根据权利要求4所述的一种基于有限元模型数值仿真的PCR基座制造参数优化方法,其特征在于:所述设定的搜索策略包括网格搜索、粒子群算法、模拟退火或蚁群算法。5. The method for optimizing the manufacturing parameters of a PCR base based on finite element model numerical simulation according to claim 4, wherein the set search strategy comprises grid search, particle swarm algorithm, simulated annealing or ant Group algorithm. 6.根据权利要求2所述的一种基于有限元模型数值仿真的PCR基座制造参数优化方法,其特征在于:所述步骤S6的具体内容为:判断是否满足停止条件(1)、(2),若满足则停止计算,输出优化集合O{V1、V2、V3…Vn、ess、σ、vup、vdown、ξ、θ},并进行优化结果处理,完成PCR基座制造参数优化;否则更新变量返回步骤S3。6. a kind of PCR base manufacturing parameter optimization method based on finite element model numerical simulation according to claim 2, is characterized in that: the concrete content of described step S6 is: judge whether to satisfy stop condition (1), (2) ), if it is satisfied, stop the calculation, output the optimization set O{V 1 , V 2 , V 3 ... V n , ess , σ, v up , v down , ξ, θ}, and process the optimization results to complete the PCR base The seat manufacturing parameters are optimized; otherwise, the variables are updated and return to step S3. 7.根据权利要求5所述的一种基于有限元模型数值仿真的PCR基座制造参数优化方法,其特征在于:所述优化结果处理的具体内容为:7. a kind of PCR base manufacturing parameter optimization method based on finite element model numerical simulation according to claim 5, is characterized in that: the specific content of described optimization result processing is: 根据计算结果,将所有符合式(1)的输出值O1k{V1、V2、V3…Vn、essk、σk、vupk、vdownk、ξk、θk}{0<k≤n2︱k∈Z}输入集合O,根据θk{0<k≤n2︱k∈Z}从大到小的方式进行集合的重新排序,输出集合O提交给用户;根据用户定制的优化原则,在集合O中,根据设计需求选择最合理的制造参数,完成优化。According to the calculation result, all output values O 1k {V 1 , V 2 , V 3 . . . V n , essk , σ k , v upk , v downk , ξ k , θ k }{0< k≤n 2 ︱k∈Z} input set O, reorder the set from large to small according to θ k {0<k≤n 2 ︱k∈Z}, and submit the output set O to the user; customized according to the user In the set O, the most reasonable manufacturing parameters are selected according to the design requirements to complete the optimization. 当希望性价比更高则根据其性价比系数θ作为主要依据,若希望有更好的温度均匀性则以均匀性系数ξ作为主要依据,同理希望有更快的升降温速率则考虑vupk、vdownk,希望有更好的温度精度则需要优先考虑ess、σ最小化。When you want a higher cost performance, use the cost-effectiveness coefficient θ as the main basis; if you want better temperature uniformity, use the uniformity coefficient ξ as the main basis; similarly, if you want a faster heating and cooling rate, consider v upk , v downk , if you want better temperature accuracy, you need to prioritize ess and σ minimization.
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