PCR thermal cycling system based on heat accumulation and control method thereof

Abstract

The present application relates to a PCR thermal cycling system based on heat storage and a control method thereof, and belongs to the technical field of molecular diagnostic hardware and precise temperature control, comprising: a first thermal unit for carrying samples; a second thermal unit with a larger heat capacity than the first thermal unit; a heat transfer assembly arranged between the first thermal unit and the second thermal unit, comprising at least two series-connected thermoelectric conversion elements; and a controller electrically connected with the heat transfer assembly. The controller controls the heat transfer assembly to be powered in a first direction in the cooling stage, so as to transfer heat from the first thermal unit to the second thermal unit for accumulation; and controls the heat transfer assembly to be powered in a second direction in the heating stage, so as to reversely transfer the accumulated heat to the first thermal unit, thereby forming a bidirectional circulation of heat. The system is not configured with a fan, and the heat is transferred in a solid state without a fan. The present application realizes waste heat recovery through bidirectional circulation and transfer of heat, reduces energy consumption, eliminates the interference of fan vibration on optical detection, and improves the heating and cooling rates and temperature control accuracy.

Description

Technical Field

[0001] This invention relates to molecular diagnostic hardware and precision temperature control technology, specifically to a PCR thermal cycling system based on heat storage and its control method. Background Technology

[0002] Polymerase chain reaction (PCR) is one of the most fundamental nucleic acid amplification technologies in molecular biology and molecular diagnostics. PCR reactions require frequent cycling between three different temperature platforms, typically including a denaturation temperature of around 95°C, an annealing temperature of around 55°C, and an extension temperature of around 72°C. The heating / cooling rate and temperature control precision of the thermal cycling system directly determine the total PCR reaction time and the reliability of the detection results.

[0003] Traditional PCR thermal cycling systems typically employ an air convection cooling architecture consisting of a sample block, a thermoelectric cooler (TEC), aluminum finned heat sinks, and a forced convection fan. However, in practical engineering operations, this architecture suffers from the following insurmountable physical bottlenecks: 1. The bottleneck of inefficient airflow convection heat transfer. The core logic of traditional cooling systems is to ultimately expel the heat from the sample block into the air. However, air has an extremely low thermal conductivity (approximately 0.026 W / (m·K)). Even with forced convection using high-speed fans, its convective heat transfer coefficient is still far lower than that of solid conduction and liquid convection. This makes the air interface the biggest "thermal resistance bottleneck" in the entire temperature control path, greatly limiting further breakthroughs in cooling rate. In rapid PCR applications that pursue "second-level" temperature changes, the inefficiency of airflow convection heat dissipation has become an insurmountable physical ceiling.

[0004] 2. One-way energy waste during the heating phase. In traditional systems, heat exhausted to the air by fans during the cooling phase is completely dissipated into the environment; this heat cannot be recovered or stored. In the subsequent secondary heating phase, the heater must start from scratch, consuming a large amount of electrical energy to reheat, without any form of recovery or reuse of the waste heat from the previous cycle. This not only results in significant energy waste but also keeps the instrument's peak power demand consistently high.

[0005] 3. Interference of fan mechanical vibration on optical detection. Rapid temperature-changing PCR usually integrates real-time quantitative PCR. The high-frequency mechanical vibration caused by the high-power fan rotating at high speed can easily cause micron-level mechanical displacement in the micro-reaction tube, which in turn causes signal jitter and noise in the excitation and emission optical paths, seriously affecting the accuracy and repeatability of quantitative detection results.

[0006] Furthermore, while existing technologies have proposed solutions to save energy by utilizing semiconductor elements to transfer heat between different reaction orifices (e.g., US Patent 11,806,719 B2), these technologies essentially belong to the "multi-hole space offset heat transfer" mode. This requires the simultaneous existence of heating and cooling orifices within the system to mutually transfer heat, which limits them to independent multi-hole control architectures at the microfluidic or chip level, making them unsuitable for scenarios involving overall synchronous extreme temperature changes across the entire macroscopic sample block.

[0007] Therefore, how to break free from the traditional heat dissipation constraints of "relying on airflow to remove heat" and design a fanless solid-state PCR thermal cycling system that is entirely based on a high thermal conductivity solid medium for instantaneous heat extraction and can achieve energy recovery in both heating and cooling cycles is a major technical challenge that the industry urgently needs to overcome. Summary of the Invention

[0008] The technical problem to be solved by the present invention is to provide a PCR thermal cycling system based on heat storage and its control method, which aims to overcome the technical defects of traditional PCR thermal cycling systems, such as low heat transfer efficiency, unidirectional energy waste, and fan vibration interference with optical detection caused by reliance on air convection for heat dissipation.

[0009] The technical solution of the present invention to solve the above-mentioned technical problems is as follows: A PCR thermal cycling system based on heat storage includes: The first thermal unit is used to hold the sample to be heated and to exchange heat with it; The second heating unit is used to store heat from the first heating unit during the cooling phase and release heat to the first heating unit as a heat source during the subsequent heating phase. The heat capacity of the second heating element is greater than that of the first heating element; A heat transfer assembly is disposed between the first heat unit and the second heat unit, the heat transfer assembly comprising at least two stages of thermoelectric conversion elements connected in series; The controller, electrically connected to the heat transfer component, is used to control the heat transfer component to be energized in a first direction during the cooling phase, so that heat is transferred from the first heat unit to the second heat unit for storage via the heat transfer component; and to control the heat transfer component to be energized in a second direction opposite to the first direction during the heating phase, so that heat stored in the second heat unit is transferred in the opposite direction via the heat transfer component to the first heat unit. Excluding fluid drive devices used for active cooling.

[0010] The beneficial effects of this invention are as follows: By setting a second heat unit as a heat storage body and configuring at least two stages of heat transfer components connected in series, during the cooling stage, the controller controls the heat transfer components to be energized in the first direction, actively pumping the heat from the first heat unit to the second heat unit for storage. In the subsequent heating stage, the controller controls the heat transfer components to be energized in the second direction in reverse, pumping the heat stored in the second heat unit back to the first heat unit. This achieves bidirectional circulation and time-domain shift of heat between the cooling and heating stages, enabling the heating stage to utilize waste heat recovered from the previous cooling cycle for auxiliary heating. The heating avoids the energy waste caused by the one-way heat dissipation to the air in traditional PCR thermal cycling systems, reducing the overall energy consumption of the machine. At the same time, the system does not have a fluid drive device for active heat dissipation. The heat transfer path is entirely composed of solid media (first thermal unit, heat transfer component, second thermal unit), eliminating the bottleneck of convective heat transfer at the air interface. The heat transfer efficiency is several times higher than that of traditional air convection cooling architecture. Furthermore, since there are no moving parts such as fans, the interference of mechanical vibration on the fluorescence detection optical path is eliminated at the source, improving the stability of detection results and the service life of the equipment.

[0011] Furthermore, the thermoelectric conversion element is a semiconductor refrigeration chip, and the semiconductor refrigeration chips are stacked vertically. In two adjacent thermoelectric cooler layers, the cold side of the upper thermoelectric cooler layer is in contact with the hot side of the lower thermoelectric cooler layer; The hot side of the uppermost semiconductor cooling chip is in contact with the first thermal unit, and the cold side of the lowermost semiconductor cooling chip is in contact with the second thermal unit.

[0012] The beneficial effects of adopting the above-mentioned further scheme are as follows: by stacking at least two semiconductor cooling chips vertically to form a cascaded solid-state heat pump, the multi-stage semiconductor cooling chips are connected in series electrically and work together thermally, which can achieve a pumping temperature difference and heat transport capacity far exceeding that of a single-stage TEC; the uppermost hot surface is attached to the first thermal unit and the lowermost cold surface is attached to the second thermal unit, which ensures that heat can still be efficiently pumped from the first thermal unit to the second thermal unit (cooling) or pumped back from the second thermal unit to the first thermal unit (heating) under fanless conditions, meeting the rapid temperature change requirements of PCR thermal cycling.

[0013] Furthermore, the second heating element is a solid metal block, and its heat capacity is more than 50 times that of the first heating element.

[0014] The beneficial effects of adopting the above-mentioned further scheme are: the second thermal unit adopts a solid metal block with a high thermal conductivity and its heat capacity is more than 50 times that of the first thermal unit, so that the second thermal unit has sufficient heat capacity to store all the temperature change heat of multiple PCR cycles. Without relying on external convection heat dissipation, it can still maintain the thermal balance of the system in multiple cycles and ensure the continuous stability of heating and cooling performance.

[0015] Furthermore, the controller includes a feedforward compensation module. The input terminal of the feedforward compensation module is connected to a temperature sensor located at the second thermal unit, and the output terminal of the feedforward compensation module is coupled to the drive current superposition terminal of the heat transfer component. The feedforward compensation module is used to generate a feedforward compensation current based on the real-time temperature of the second thermal unit and superimpose it on the drive current of the heat transfer component.

[0016] The beneficial effects of adopting the above-mentioned further scheme are: the feedforward compensation module collects the temperature of the second thermal unit in real time, and calculates the feedforward compensation current based on its actual temperature and adds it to the drive current, which can compensate for the system temperature drift caused by the gradual increase of the temperature of the second thermal unit under fanless conditions, so that the control model remains accurate in multiple cycles.

[0017] Furthermore, the controller also includes a braking control module, the input terminal of which is connected to a second temperature sensor located at the first thermal unit, and the output terminal of which is coupled to the drive current superposition terminal of the heat transfer component.

[0018] The beneficial effect of adopting the above-mentioned further solution is that by adding a braking control module, reverse braking can be applied when the temperature approaches the target platform, which can counteract the thermal inertia caused by the large heat capacity of the system and prevent temperature overshoot.

[0019] Furthermore, the braking control module includes a braking judgment unit and a braking current output unit; The input terminal of the braking judgment unit is connected to the second temperature sensor located at the first thermal unit, and the output terminal of the braking judgment unit is connected to the input terminal of the braking current output unit. It is used to generate a braking trigger signal within the braking window before the temperature of the first thermal unit enters the target temperature platform. The starting point of the braking window is adaptively adjusted according to the real-time temperature of the second thermal unit. The output terminal of the braking current output unit is coupled to the drive current superposition terminal of the heat transfer component, and is used to generate a reverse braking current in response to the braking trigger signal and superimpose it on the drive current of the heat transfer component.

[0020] The beneficial effects of adopting the above-mentioned further scheme are: the braking judgment unit adaptively adjusts the starting position of the braking window according to the real-time temperature of the second thermal unit, and the braking current output unit generates a reverse braking current in response to the braking trigger signal, thereby realizing the adaptive adjustment of the braking timing - when the temperature of the second thermal unit is higher and the heat conduction of the system is slower, the braking starting point is adaptively advanced, so as to always achieve precise temperature control without overshoot in multiple cycles.

[0021] Furthermore, the controller also includes a PID control module, which includes an integral separation control structure; The integral separation control structure includes an integral unit and an integral switch unit; The input terminal of the integration unit is connected to a second temperature sensor located at the first heating unit, and is used to integrate the temperature difference between the real-time temperature of the first heating unit and the target temperature over time to generate an integral control quantity. The output terminal of the integration unit is connected to the input terminal of the integration switch unit; The output terminal of the integral switch unit is coupled to the drive current superposition terminal of the heat transfer component; When the absolute value of the temperature change rate of the first thermal unit is greater than a preset threshold, the integral switch unit is disconnected and the integral control quantity is blocked. When the absolute value of the temperature change rate of the first thermal unit is less than or equal to the preset threshold, the integral switch unit closes, the integral control quantity is used as the integral input of the PID control module, and after being converted into a current signal by the signal processing stage of the PID control module, it is output to the drive current of the heat transfer component.

[0022] The beneficial effects of adopting the above-mentioned further scheme are as follows: The PID control module adopts an integral separation control structure. When the temperature change rate is large (in the temperature change coasting and braking sections), the integral switch unit is disconnected, blocking the output of the integral control quantity, thus avoiding integral saturation and temperature overshoot caused by the huge thermal inertia of the large heat capacity system. When the temperature change rate is small (entering the steady-state plateau period), the integral switch unit is closed, the integral control quantity is output normally, eliminating the steady-state temperature error, and taking into account both the anti-overshoot performance in the rapid temperature change stage and the temperature control accuracy in the steady-state stage.

[0023] A temperature control method for a PCR thermal cycling system based on heat storage includes: Cooling step: Power the heat transfer component along the first direction to transfer heat from the first heat unit to the second heat unit for storage via the heat transfer component; Heating step: The heat transfer component is energized in a second direction opposite to the first direction, and the heat accumulated in the second heat unit is transferred in the opposite direction to the first heat unit through the heat transfer component; The cooling and heating steps are repeated to form a bidirectional heat transfer cycle.

[0024] The beneficial effects of this invention are: by accumulating heat in the second thermal unit through the cooling step, and transferring the accumulated heat back to the first thermal unit in the heating step, the heat in the PCR thermal cycle is realized through time-domain transfer and bidirectional recycling. The heating stage utilizes the waste heat recovered from the previous cooling cycle, reducing system energy consumption. At the same time, the all-solid heat transfer path eliminates the thermal resistance of the air interface, and the heating and cooling rates are significantly improved.

[0025] Furthermore, the cooling step also includes braking control: Real-time detection of the temperature change rate of the first thermal unit; When the temperature of the first thermal unit approaches a preset threshold before the target temperature, a reverse current is applied to the heat transfer component to counteract the thermal inertia of the system. The preset threshold is determined based on the system thermal resistance-capacitance time constant and the current temperature change rate.

[0026] The beneficial effects of adopting the above-mentioned further scheme are: adding braking control in the cooling step, applying reverse current when the temperature approaches the preset threshold before the target temperature, using electrical "braking" to actively counteract the thermal inertia of the system, so that the temperature curve cuts into the target platform steeply and without overshoot; the preset threshold is dynamically determined according to the thermal resistance-capacitance time constant of the system and the current temperature change rate, which can adapt to the thermal inertia differences under different operating conditions and ensure the consistency of temperature control accuracy.

[0027] Furthermore, in the cooling step: The total current of the heat transfer component is synthesized from the PID feedback term, the feedforward compensation term, and the damping braking term. The feedforward compensation term is determined by the real-time temperatures of the first and second thermal units; The amplitude of the damping braking term is determined by the temperature change rate of the first thermal unit, and the activation condition of the damping braking term is determined by the real-time temperature of the second thermal unit.

[0028] The beneficial effects of adopting the above-mentioned further scheme are as follows: the total current in the cooling step is synthesized by three terms: PID feedback, feedforward compensation, and damping braking, which realizes fine control of the driving current of the heat transfer component: the PID feedback is adjusted in a closed loop according to the real-time temperature difference to ensure temperature control accuracy; the feedforward compensation is jointly determined by the real-time temperatures of the first and second thermal units, enabling the controller to dynamically adjust the feedforward compensation amount according to the real-time temperature difference between the sample block and the heat storage metal block. Compared with the traditional feedforward algorithm that assumes the temperature of the heat dissipation end to be a fixed ambient temperature, this scheme can more accurately compensate for system drift under fanless conditions; the amplitude of the damping braking term is determined by the temperature change rate of the first thermal unit, and the activation condition is determined by the real-time temperature of the second thermal unit. When the temperature change rate is greater, the braking force is stronger. When the temperature of the second thermal unit rises, causing the system heat conduction to slow down, the braking start point is adaptively advanced, realizing dual precise control of braking timing and braking force, ensuring that overshoot-free and precise temperature control is always achieved in multiple cycles. Attached Figure Description

[0029] Figure 1 This is a schematic diagram of the PCR thermal cycling system based on heat storage according to the present invention.

[0030] The attached diagram lists the components represented by each number as follows: 1. Second heating unit; 2. Heat transfer component; 3. First heating unit; 4. Temperature sensor 2. Detailed Implementation

[0031] The principles and features of the present invention are described below. The examples given are only for explaining the present invention and are not intended to limit the scope of the present invention.

[0032] Example 1 like Figure 1 As shown, the PCR thermal cycling system based on heat storage provided in this embodiment includes, from bottom to top: a second thermal unit 1, a heat transfer component 2, and a first thermal unit 3.

[0033] The first heating unit 3 is used to hold the sample to be heated and to exchange heat with it. The first heating unit 3 is made of gold-plated copper and is designed to be minimal in weight, with extremely low intrinsic heat capacity. The upper surface of the first heating unit 3 can be provided with grooves that match the shape of the sample (such as a PCR 96-well plate, PCR single tube, connecting tube, or microfluidic chip) or be a flat surface to hold the sample to be reacted and achieve good heat conduction.

[0034] The second heating unit 1 is a single, solid metal block with high thermal conductivity, made of copper or aluminum alloy. The physical heat capacity of the second heating unit 1 is set to be more than 50 times the total heat capacity of the first heating unit 3, specifically designed to rigidly accumulate or release all the temperature-changing heat from multiple PCR cycles without any external convection. The upper surface of the second heating unit 1 is precision-machined to ensure a high degree of flatness, guaranteeing a tight fit with the lower surface of the heat transfer component 2. The system does not include any cooling fans or fluid-driven devices for active cooling.

[0035] The heat transfer component 2 is disposed between the first heating unit 3 and the second heating unit 1. For example... Figure 1 As shown, the heat transfer assembly 2 includes at least two stages of thermoelectric conversion elements connected in series.

[0036] In this embodiment, the thermoelectric conversion element is a thermoelectric cooler (TEC), and the TECs are stacked vertically. The hot surface of the topmost TEC is in contact with the lower surface of the first thermal unit 3, and the cold surface of the bottommost TEC is in contact with the upper surface of the second thermal unit 1. In adjacent TECs, the cold surface of the upper TEC is in contact with the hot surface of the lower TEC. Thermally conductive interface materials (such as thermal grease or thermal pads) are provided between adjacent TECs and between the TECs and the first or second thermal unit to reduce contact thermal resistance.

[0037] A controller (not shown in the figure) is electrically connected to the heat transfer assembly 2. During the cooling phase, the controller controls the heat transfer assembly 2 to be energized in a first direction, causing heat to be transferred from the first heat transfer unit 3 to the second heat transfer unit 1 for storage. In the subsequent heating phase, the controller controls the heat transfer assembly 2 to be energized in a second direction opposite to the first direction, causing the heat stored in the second heat transfer unit 1 to be transferred back to the first heat transfer unit 3 via the heat transfer assembly 2. The controller can be implemented using a microcontroller (MCU), digital signal processor (DSP), or field-programmable gate array (FPGA).

[0038] Temperature sensor 2 (not shown in the figure) is provided at the first heating unit 3 and the second heating unit 1, respectively, to monitor the temperature of the first heating unit 3 and the second heating unit 1 in real time. Temperature sensor 2 (4) and temperature sensor 1 are preferably high-precision thermistors (such as 10kΩ NTC thermistors) or thermocouples.

[0039] Example 2 During the cooling phase, the controller supplies a current in the first direction to the heat transfer component 2. At this time, the upper and lower semiconductor cooling chips work simultaneously, forming a heat pumping direction from the first thermal unit 3 to the second thermal unit 1.

[0040] The heat from the first thermal unit 3 travels along the path from the hot surface of the topmost thermoelectric cooler to the cold surface of the topmost thermoelectric cooler, then to the hot surface of the next thermoelectric cooler, and finally back to the cold surface of the next thermoelectric cooler, before being actively pumped to the second thermal unit 1 for storage. The entire heat transfer path is a solid medium with high thermal conductivity (metal and semiconductor materials), and there is no air convection interface, resulting in extremely low thermal resistance, allowing heat to be quickly extracted from the first thermal unit.

[0041] During this process, the controller collects the temperature of the first heating unit 3 in real time. Temperature of the second heating unit 1 .when When the temperature drops to a preset threshold close to the target low point temperature (such as annealing temperature of 55℃ or extension temperature of 72℃), the controller starts the feedforward predictive damping control algorithm, and applies a weak reverse current to the heat transfer component 2 to perform active electrical "braking", instantly offsetting the residual thermal inertia of the system, so that the temperature curve cuts into the low point platform steeply and without overshoot.

[0042] Example 3 During the heating phase, the controller supplies a current in a second direction, opposite to the first direction, to the heat transfer component 2. At this time, the heat pumping direction is reversed, changing from the second heating unit 1 to the first heating unit 3.

[0043] During the previous cooling phase, the second thermal unit 1 had accumulated a large amount of heat, and its temperature had risen significantly. The controller uses the second thermal unit 1 as an "active heat source base" to apply a large current to the upper semiconductor cooling chip to forcefully pump heat upwards. At the same time, the lower semiconductor cooling chip cooperates by outputting a specific drive current to pump the energy accumulated in the second thermal unit 1 back to the first thermal unit 3.

[0044] The heating phase not only relies on electrical energy for heating, but also incorporates the "storage waste heat" recovered from the previous cooling phase. This allows the secondary heating slope to achieve an ultra-high temperature change rate even with a metal block possessing a large heat capacity, while significantly reducing the overall energy consumption of the unit. The cooling and heating modes alternate, forming a complete two-way heat cycle.

[0045] Example 4: The controller of this invention employs an improved feedforward predictive damping algorithm to control the energizing current of the heat transfer component 2, i.e., the total control current. Total control current By PID feedback term Feedforward compensation term and damping braking items It consists of three parts.

[0046] The formula for calculating the total control current is: .

[0047] (1) PID feedback term Calculation: The controller calculates the target platform temperature in real time. Real-time temperature detection with the first heating unit 3 Temperature difference between .

[0048] PID feedback item That is, the PID feedback term current: .

[0049] in, , , These are the proportional gain coefficient, integral gain coefficient, and differential gain coefficient, respectively.

[0050] Unlike traditional PID algorithms, this invention employs an integral separation control strategy: during the temperature-changing coasting phase (i.e., the rapid temperature change phase where the temperature of the first thermal unit 3 is far from the target temperature) and the braking phase (i.e., the deceleration phase before reaching the target temperature), the controller forces the integral gain coefficient to be set to... =0; Activated only when the temperature smoothly enters the steady-state plateau period (i.e., the temperature of the first thermal unit 3 has entered the small error band near the target temperature). This strategy effectively avoids severe integral saturation and temperature overshoot caused by large heat capacity systems.

[0051] The specific implementation of integral separation control is as follows: when the absolute value of the temperature change rate of the first thermal unit 3 is greater than a preset threshold, the integral switch unit is disconnected, and the integral control quantity is blocked; when the absolute value of the temperature change rate of the first thermal unit 3 is less than or equal to the preset threshold, the integral switch unit is closed, and the integral control quantity is output to the drive current of the heat transfer component 2. The preset threshold is preset according to the thermal inertia of the system and the desired control accuracy. In a specific embodiment, the preset threshold is 3 to 10℃ / s.

[0052] (2) Feedforward compensation term Calculation The controller is based on the desired temperature slope of the target curve. System equivalent heat capacity The sum of the rigid thermal resistances of each layer of the heat transfer component 2 The inherent heat pumping characteristic coefficient of thermoelectric conversion elements as well as Calculate the feedforward compensation current (i.e., the feedforward compensation term) The calculation formula is as follows: .

[0053] Unlike traditional feedforward algorithms that assume the heat dissipation temperature to be an environmental constant. (Right now Unlike the present invention, the present invention has different characteristics. This refers to the real-time temperature variable of the second thermal unit 1. That is, the controller collects the actual temperature in real time through a temperature sensor installed at the second heating unit 1. The values ​​are then substituted into the calculation. Since the system operates without a fan, the temperature of the second thermal unit 1 will gradually increase during multiple PCR cycles. Incorporating its real-time temperature into the feedforward model can effectively eliminate the temperature drift effect after multiple consecutive cycles.

[0054] (3) Damping braking item Calculation The controller monitors the temperature change rate of the first heating unit 3 in real time. And calculate the temperature difference threshold for early braking: ΔT p re(t) = · .

[0055] in, Let be the system's thermal resistance-capacitance time constant, which is a time-varying function of the temperature of the second thermal unit 1: .

[0056] In the formula, The initial time constant, The initial temperature of the second heating unit 1. This is the temperature compensation coefficient.

[0057] When the temperature of the first heating unit 3 Still far from the target temperature ( > + When ), the damping term does not intervene. =0.

[0058] When the temperature of the first heating unit 3 enters the braking window ( ≤ ≤ + When this occurs, the damping term intervenes: = .

[0059] in, This is the damping braking gain coefficient. () represents the sign function, ensuring that the direction of the braking current is always opposite to the direction of motion. Unlike traditional linear damping, this invention uses a quadratic velocity mapping, resulting in greater braking force at the moment of braking and a smoother drop in braking force near the plateau. Simultaneously, due to the time constant... As the temperature of the second heating unit 1 adapts, the algorithm automatically adjusts the braking point earlier and earlier in multiple cycles, effectively preventing overshoot caused by the slowing of heat conduction due to the second heating unit 1 getting hotter in each cycle.

[0060] Example 5 In one specific embodiment of the present invention, the controller includes a feedforward compensation module. The input terminal of the feedforward compensation module is connected to a temperature sensor disposed at the second thermal unit 1, and the output terminal of the feedforward compensation module is coupled to the drive current superposition terminal of the heat transfer component 2.

[0061] The feedforward compensation module generates a feedforward compensation current based on the real-time temperatures of the first thermal unit 3 and the second thermal unit 1. And it is added to the driving current of the heat transfer component 2.

[0062] Specifically, the feedforward compensation current The calculation method is as described in Example 4. Since the temperature of the second thermal unit 1 increases sequentially in multiple PCR cycles, the feedforward compensation module collects the current temperature of the second thermal unit 1 in real time and substitutes it into the formula to calculate the feedforward compensation current. It can effectively eliminate the feedforward model failure problem caused by temperature changes at the heat dissipation end under fanless conditions.

[0063] Example 6 In one specific embodiment of the present invention, the controller further includes a braking control module. The input terminal of the braking control module is connected to a temperature sensor 4 disposed at the first thermal unit 3, and the output terminal of the braking control module is coupled to the drive current superposition terminal of the heat transfer component 2.

[0064] The braking control module includes a braking judgment unit and a braking current output unit.

[0065] The input terminal of the braking judgment unit is connected to the temperature sensor 4 located at the first heating unit 3, and the output terminal of the braking judgment unit is connected to the input terminal of the braking current output unit. The braking judgment unit is used to generate a braking trigger signal within the braking window before the temperature of the first heating unit 3 reaches the target temperature platform. The starting temperature threshold of the braking window is adaptively adjusted according to the real-time temperature of the second heating unit 1.

[0066] Specifically, when the temperature of the second thermal unit 1 increases, causing the system's heat conduction to slow down, the braking initiation temperature threshold is adaptively increased (i.e., braking begins earlier).

[0067] The output terminal of the braking current output unit is coupled to the drive current superposition terminal of the heat transfer component 2, and is used to generate a reverse braking current in response to the braking trigger signal and superimpose it on the drive current of the heat transfer component 2.

[0068] Example 7 In one specific embodiment of the present invention, the controller further includes a PID control module, which includes an integral separation control structure.

[0069] The integral separation control structure includes an integral unit and an integral switch unit.

[0070] The input terminal of the integrator is connected to the temperature sensor 4 located at the first heating unit 3, and is used to integrate the temperature difference between the real-time temperature of the first heating unit 3 and the target temperature over time to generate an integral control quantity. The output terminal of the integrator is connected to the input terminal of the integral switch unit.

[0071] The output of the integral switch unit is coupled to the drive current superposition terminal of the heat transfer component 2. When the absolute value of the temperature change rate of the first heat unit 3 is greater than a preset threshold, the integral switch unit is disconnected, and the integral control quantity is blocked; when the absolute value of the temperature change rate of the first heat unit 3 is less than or equal to the preset threshold, the integral switch unit is closed, and the integral control quantity is used as the integral input of the PID control module. After being converted into a current signal by the signal processing stage of the PID control module, it is output to the drive current of the heat transfer component 2.

[0072] Through the above integral separation control structure, the integral term is cut off during the variable temperature coasting and braking phases to avoid integral saturation and temperature overshoot caused by the huge thermal inertia of the large heat capacity system; during the steady-state plateau period, the integral term is activated to eliminate steady-state temperature error.

[0073] Example 8 This embodiment provides a temperature control method for a PCR thermal cycling system based on the above-mentioned heat storage method, including the following steps: Cooling step: Power the heat transfer component 2 along the first direction to transfer heat from the first heat unit 3 to the second heat unit 1 for storage.

[0074] Heating step: The heat transfer component 2 is energized in a second direction opposite to the first direction, and the heat accumulated in the second heat unit 1 is transferred in the opposite direction to the first heat unit 3 via the heat transfer component 2.

[0075] Repeated cooling and heating steps create a two-way heat transfer cycle.

[0076] The cooling process also includes braking control: real-time detection of the temperature change rate of the first heating unit 3; when the temperature of the first heating unit 3 approaches a preset threshold before the target temperature, a reverse current is applied to the heat transfer component 2 to counteract the system's thermal inertia; the preset threshold is determined based on the system's thermal resistance-capacitance time constant and the current temperature change rate. Specifically, the preset threshold is equal to the product of the system's thermal resistance-capacitance time constant and the absolute value of the current temperature change rate.

[0077] In the cooling step, the total current of the heat transfer component 2 is synthesized by a PID feedback term, a feedforward compensation term, and a damping braking term; the feedforward compensation term is determined by the real-time temperature of the first thermal unit and the real-time temperature of the second thermal unit; the amplitude of the damping braking term is determined by the temperature change rate of the first thermal unit, and the activation condition of the damping braking term is determined by the real-time temperature of the second thermal unit.

[0078] The PCR thermal cycling system and its control method based on heat storage provided by this invention can be widely used in PCR nucleic acid detection equipment in various molecular diagnostics and life science research fields. This system is compact, fanless, energy-efficient, and has high temperature control accuracy. It is particularly suitable for vibration-sensitive and portable real-time quantitative PCR detection scenarios, demonstrating significant industrial practical value and broad market application prospects.

[0079] Although embodiments of the present invention have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting the present invention. Those skilled in the art can make changes, modifications, substitutions and variations to the above embodiments within the scope of the present invention.

Claims

1. A PCR thermal cycling system based on heat storage, characterized in that, include: The first thermal unit (3) is used to carry the sample to be heated and to exchange heat with it; The second heating unit (1) is used to store heat from the first heating unit (3) during the cooling phase and release heat to the first heating unit (3) as a heat source during the subsequent heating phase. The heat capacity of the second heat unit (1) is greater than that of the first heat unit (3); A heat transfer assembly (2) is disposed between the first heat unit (3) and the second heat unit (1), and the heat transfer assembly (2) includes at least two thermoelectric conversion elements connected in series; The controller is electrically connected to the heat transfer component (2) and is used to control the heat transfer component (2) to be energized in the first direction during the cooling stage, so that heat is transferred from the first heat unit (3) to the second heat unit (1) for storage via the heat transfer component (2); During the heating phase, the heat transfer component (2) is energized in a second direction opposite to the first direction, so that the heat stored in the second heat unit (1) is transferred in the opposite direction to the first heat unit (3) via the heat transfer component (2). Excluding fluid drive devices used for active cooling.

2. The PCR thermal cycling system based on heat storage according to claim 1, characterized in that, The thermoelectric conversion element is a semiconductor refrigeration chip, and the semiconductor refrigeration chips are stacked vertically. In two adjacent thermoelectric cooler layers, the cold side of the upper thermoelectric cooler layer is in contact with the hot side of the lower thermoelectric cooler layer; The hot side of the uppermost semiconductor cooling chip is in contact with the first thermal unit (3), and the cold side of the lowermost semiconductor cooling chip is in contact with the second thermal unit (1).

3. The PCR thermal cycling system based on heat storage according to claim 1, characterized in that, The second thermal unit (1) is a solid metal block, and its heat capacity is more than 50 times that of the first thermal unit (3).

4. The PCR thermal cycling system based on heat storage according to claim 1, characterized in that, The controller includes a feedforward compensation module. The input terminal of the feedforward compensation module is connected to a temperature sensor located at the second thermal unit (1). The output terminal of the feedforward compensation module is coupled to the drive current superposition terminal of the heat transfer component (2) for generating a feedforward compensation current based on the real-time temperature of the second thermal unit (1) and superimposing it on the drive current of the heat transfer component (2).

5. The PCR thermal cycling system based on heat storage according to claim 4, characterized in that, The controller also includes a braking control module. The input end of the braking control module is connected to the second temperature sensor (4) located at the first thermal unit (3). The output end of the braking control module is coupled to the driving current superposition terminal of the heat transfer component (2).

6. The PCR thermal cycling system based on heat storage according to claim 5, characterized in that, The braking control module includes a braking judgment unit and a braking current output unit; The input end of the braking judgment unit is connected to the temperature sensor 2 (4) located at the first thermal unit (3), and the output end of the braking judgment unit is connected to the input end of the braking current output unit. It is used to generate a braking trigger signal in the braking window before the temperature of the first thermal unit (3) enters the target temperature platform. The starting point of the braking window is adaptively adjusted according to the real-time temperature of the second thermal unit (1). The output terminal of the braking current output unit is coupled to the driving current superposition terminal of the heat transfer component (2) to generate a reverse braking current in response to the braking trigger signal and superimpose it on the driving current of the heat transfer component (2).

7. The PCR thermal cycling system based on heat storage according to claim 1, characterized in that, The controller also includes a PID control module, which includes an integral separation control structure. The integral separation control structure includes an integral unit and an integral switch unit; The input terminal of the integration unit is connected to the second temperature sensor (4) located at the first thermal unit (3), and is used to integrate the temperature difference between the real-time temperature of the first thermal unit (3) and the target temperature over time to generate an integral control quantity. The output terminal of the integration unit is connected to the input terminal of the integration switch unit; The output terminal of the integral switch unit is coupled to the drive current superposition terminal of the heat transfer component (2); When the absolute value of the temperature change rate of the first thermal unit (3) is greater than the preset threshold, the integral switch unit is disconnected and the integral control quantity is blocked. When the absolute value of the temperature change rate of the first thermal unit (3) is less than or equal to the preset threshold, the integral switch unit closes, the integral control quantity is used as the integral input of the PID control module, and after being converted into a current signal by the signal processing link of the PID control module, it is output to the driving current of the heat transfer component (2).

8. A temperature control method for a PCR thermal cycling system based on heat storage as described in claim 1, characterized in that, include: Cooling step: Power the heat transfer component (2) along the first direction to transfer heat from the first heat unit (3) to the second heat unit (1) for storage via the heat transfer component (2); Heating step: The heat transfer component (2) is energized in a second direction opposite to the first direction, and the heat accumulated in the second heat unit (1) is transferred in the opposite direction to the first heat unit (3) through the heat transfer component (2). The cooling and heating steps are repeated to form a bidirectional heat transfer cycle.

9. The temperature control method for the PCR thermal cycling system based on heat storage according to claim 8, characterized in that, The cooling process also includes braking control: Real-time detection of the temperature change rate of the first thermal unit (3); When the temperature of the first thermal unit (3) approaches a preset threshold before the target temperature, a reverse current is applied to the heat transfer component (2) to counteract the thermal inertia of the system. The preset threshold is determined based on the system thermal resistance-capacitance time constant and the current temperature change rate.

10. The temperature control method for the PCR thermal cycling system based on heat storage according to claim 8, characterized in that, In the cooling step: The total current of the heat transfer component (2) is synthesized by the PID feedback term, the feedforward compensation term, and the damping braking term; The feedforward compensation term is determined by the real-time temperatures of the first thermal unit (3) and the second thermal unit (1); The amplitude of the damping braking term is determined by the temperature change rate of the first thermal unit (3), and the activation condition of the damping braking term is determined by the real-time temperature of the second thermal unit (1).

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