Temperature control device, nucleic acid reaction device, temperature control method, equipment and medium
By using microfluidic chips, heat sink structures, semiconductor refrigeration sheets and heat dissipation structures in the temperature control device, and combining with particle swarm algorithms to control the temperature in real time, the problems of low temperature control accuracy and complex design in the existing technology are solved, and high-precision, fast, simple and highly robust nucleic acid reaction temperature control is achieved.
Patent Information
- Application Number
- CN202311794801.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2023-12-25
- Publication Date
- 2025-06-27
AI Technical Summary
In the prior art, the temperature control device has low accuracy and complex design, and cannot achieve high precision, fast, simple and highly robust nucleic acid reaction temperature control.
Microfluidic chips are used to control nucleic acid reaction conditions, combine heat sink structure for heat transfer, semiconductor refrigeration sheets and heat dissipation structures are used to adjust temperature, and real-time temperature control is performed through particle swarm algorithm.
It realizes high accuracy and robustness of temperature control, simplifies device design, and improves the speed and adaptability of temperature control.
Smart Images
Figure CN120209992A_ABST
Abstract
Description
Technical Field
[0001] This application belongs to the technical field of temperature control, and relates to a temperature control device, in particular to a temperature control device, a nucleic acid reaction device, a temperature control method, equipment and medium. Background Art
[0002] Medical testing has always been an important part of the medical field. By detecting and analyzing the physiological indicators, body fluids, tissues, etc. of patients, it can help doctors with early disease diagnosis, disease monitoring and evaluation of treatment effects. Among them, nucleic acid testing is an important medical testing method, which can be used to detect the nucleic acids of pathogens, such as viruses, bacteria, etc., so as to accurately and quickly diagnose infectious diseases. Nucleic acid testing devices are special equipment for nucleic acid testing, and their development benefits from the progress of multiple fields such as microfluidic technology, biosensing technology, and molecular biology technology. Microfluidic technology enables samples and reagents to flow and mix at a micro scale, thereby improving the reaction efficiency and accuracy; the development of biosensing technology makes the detection process more sensitive and rapid; the progress of molecular biology technology provides more methods and means for nucleic acid extraction and detection. However, there is still a lack of a nucleic acid reaction temperature control device with high precision, fast and simple operation and high robustness. Summary of the Invention
[0003] In view of the above-mentioned disadvantages of the prior art, the purpose of this application is to provide a temperature control device, a nucleic acid reaction device, a temperature control method, equipment and medium, which are used to solve the problems of low precision and complex design of the temperature control device in the prior art.
[0004] In a first aspect, this application provides a temperature control device, including: a microfluidic chip for controlling nucleic acid reaction conditions; a heat sink structure for heat transfer during the nucleic acid reaction; a thermoelectric cooler for adjusting the temperature of the nucleic acid reaction; and a heat dissipation structure for dissipating heat from the nucleic acid reaction.
[0005] In this application, the conditions of the nucleic acid reaction are controlled by the microfluidic chip, the heat transfer during the nucleic acid reaction process is completed by the heat sink structure, and the thermoelectric cooler and the heat dissipation structure are jointly used to adjust the temperature of the nucleic acid reaction. This kind of temperature control device has a simple design, high temperature control precision and high robustness.
[0006] In one implementation manner of the first aspect, the microfluidic chip includes a microchannel unit for compressing the reaction solution to the bottom of the microfluidic chip.
[0007] In one implementation manner of the first aspect, it further includes thermal conductive silicone, which is applied to the heat sink structure and the thermoelectric cooler to improve the heat conduction efficiency.
[0008] In an implementation of the first aspect, the microfluidic chip further includes a control unit, and the control unit is configured to solve the initial control parameters by using a particle swarm algorithm to perform real-time temperature control on the temperature control device.
[0009] In an implementation of the first aspect, the control unit includes: an initialization subunit, configured to obtain the initialized particle velocity, individual extreme value, and population extreme value; a velocity control subunit, configured to update the velocity position and calculate the fitness according to the initialized individual extreme value and population extreme value; an update control subunit, configured to update the individual extreme value and the population extreme value of the initialization subunit according to the fitness; and a result subunit, configured to obtain the processed control parameters according to the updated individual extreme value and population extreme value.
[0010] In an implementation of the first aspect, the heat dissipation structure is a segmented heat sink.
[0011] In a second aspect, the present application provides a nucleic acid reaction device, including: a nucleic acid extraction device, configured to extract nucleic acid in a sample; a fluorescence detection device, configured to perform fluorescence detection on the extracted nucleic acid; and a temperature control device, configured to control the temperatures of the nucleic acid extraction device and the fluorescence detection device, and the temperature control device is the temperature control device according to any one of the first aspect.
[0012] In a third aspect, the present application provides a temperature control method, including: obtaining initial control parameters; solving the initial control parameters by using a particle swarm algorithm to obtain processed control parameters; and controlling nucleic acid reaction conditions and temperature by using the processed control parameters.
[0013] In a fourth aspect, the present application provides an electronic device, including: a memory, configured to store a computer program; and a processor, configured to execute the computer program stored in the memory so that the electronic device executes the temperature control method according to the second aspect.
[0014] In a fifth aspect, the present application provides a computer-readable storage medium, on which a computer program is stored, and when the program is executed by a processor, the temperature control method according to the second aspect is implemented. Description of the Drawings
[0015] Figure 1 It shows a schematic structural diagram of the temperature control device according to an embodiment of the present application.
[0016] Figure 2 It shows a schematic structural diagram of the control unit according to an embodiment of the present application.
[0017] Figure 3 It shows a schematic flowchart of the control method according to an embodiment of the present application.
[0018] Figure 4 It shows a schematic structural diagram of the heat dissipation structure described in the embodiments of the present application.
[0019] Figure 5 It shows a schematic structural diagram of the nucleic acid reaction device described in the embodiments of the present application.
[0020] Figure 6 It shows a schematic flowchart of the temperature control method described in the embodiments of the present application.
[0021] Figure 7 It shows a schematic structural diagram of the electronic device described in the embodiments of the present application.
[0022] Description of component numbers
[0023] 1 Temperature control device
[0024] 11 Microfluidic chip
[0025] 111 Microchannel unit
[0026] 112 Control unit
[0027] 1121 Initialization subunit
[0028] 1122 Speed control subunit
[0029] 1123 Update control subunit
[0030] 1124 Result acquisition subunit
[0031] 12 Heat sink structure
[0032] 13 Thermoelectric cooler
[0033] 14 Heat dissipation structure
[0034] 2 Nucleic acid reaction device
[0035] 21 Nucleic acid extraction device
[0036] 22 Fluorescence detection device
[0037] 23 Temperature control device
[0038] 700 Electronic device
[0039] 710 Memory
[0040] 720 Processor
[0041] 730 Display
[0042] Steps S11 - S13 Detailed implementation manners
[0043] The following specific examples illustrate the implementation manners of the present application. Those skilled in the art can easily understand other advantages and effects of the present application from the content disclosed in this specification. The present application can also be implemented or applied through other different specific implementation manners. Various details in this specification can also be modified or changed based on different viewpoints and applications without departing from the spirit of the present application. It should be noted that, without conflict, the following embodiments and the features in the embodiments can be combined with each other.
[0044] It should be noted that the diagrams provided in the following embodiments only illustrate the basic concept of the present application in a schematic manner. Therefore, only the components related to the present application are shown in the diagrams, rather than being drawn according to the number, shape, and size of the components in actual implementation. The type, quantity, and ratio of each component in actual implementation can be arbitrarily changed, and the component layout type may also be more complex.
[0045] In medical detection and biological research, nucleic acid detection is of great significance. However, in the natural environment, due to its relatively low content, traditional methods often cannot directly detect it. Qualitative and quantitative detection of nucleic acids mostly uses polymerase chain reaction (PCR for short) to achieve. The schematic diagram of the PCR technology is shown in the figure. The sample DNA undergoes cycles in three temperature zones: denaturation (90 - 98 °C), renaturation (40 °C - 64 °C), and extension (72 °C), so that the original DNA template is exponentially amplified. PCR can achieve the measurement of DNA at extremely low concentrations, with high sensitivity and specificity, which is of great significance for the early diagnosis and treatment of disease patients. The PCR technology is easy to operate, has high sensitivity, specificity, and a large amplification ability. However, in the polymerase chain reaction, because temperature has an important impact on the PCR technology, the PCR technology also has disadvantages, that is, it cannot achieve high-precision, fast, and highly robust temperature control, and miniaturization has not been achieved yet. Currently, the PCR temperature control devices in the industry still have defects in terms of miniaturization, speed, and high robustness.
[0046] At least for the above problems, the embodiment of the present application provides a temperature control device, which includes a microfluidic chip for controlling the nucleic acid reaction conditions; a heat sink structure for heat transfer of the nucleic acid reaction; a thermoelectric cooler for adjusting the temperature of the nucleic acid reaction; and a heat dissipation structure for dissipating heat from the nucleic acid reaction.
[0047] In the embodiment of the present application, the conditions of the nucleic acid reaction are controlled by using a microfluidic chip, the heat sink structure completes the heat transfer during the nucleic acid reaction process, and the thermoelectric cooler and the heat dissipation structure are jointly used to adjust the temperature of the nucleic acid reaction. This kind of temperature control device has a simple design, high temperature control accuracy, and high robustness.
[0048] The following will describe in detail the technical solutions in the embodiments of the present application with reference to the accompanying drawings in the embodiments of the present application.
[0049] The following embodiments of the present application provide a temperature control device. Figure 1 It is shown as the structural schematic diagram of the temperature control device described in the embodiments of the present application. As Figure 1 shown, the temperature control device 1 includes a microfluidic chip 11, a heat sink structure 12, a thermoelectric cooler 13, and a heat dissipation structure 14.
[0050] The microfluidic chip 11 is used to control the nucleic acid reaction conditions. Optionally, the nucleic acid reaction is a polymerase chain reaction, which is used to detect the nucleic acid of pathogens, such as viruses, bacteria, etc., so as to accurately and quickly diagnose infectious diseases.
[0051] The heat sink structure 12 is used for heat transfer of the nucleic acid reaction. Among them, the heat sink structure 12 is used to provide stable heat to maintain the reaction temperature on the chip. It can effectively disperse and conduct heat to ensure that the temperature on the microfluidic chip 11 is uniform and stable.
[0052] The thermoelectric cooler 13 is used to adjust the temperature of the nucleic acid reaction. Optionally, the thermoelectric cooler 13 provides a cooling or heating effect according to needs through the Peltier effect, so as to precisely control the temperature on the microfluidic chip 11.
[0053] The heat dissipation structure 14 is used to dissipate heat for the nucleic acid reaction. Optionally, the heat dissipation structure 14 can effectively dissipate the excess heat to the external environment to prevent the device from being affected by excessive temperature and ensure its normal operation.
[0054] In the embodiments of the present application, the microfluidic chip 11 is used to control the conditions of the nucleic acid reaction, the heat sink structure 12 completes the heat transfer during the nucleic acid reaction process, and the thermoelectric cooler 13 and the heat dissipation structure 14 are jointly used to adjust the temperature of the nucleic acid reaction. This kind of temperature control device 1 has a simple design, high temperature control accuracy, and high robustness.
[0055] In an embodiment of the present application, the microfluidic chip 11 includes a microchannel unit 111, and the microchannel unit 111 is used to compress the reaction solution to the bottom of the microfluidic chip 11. Optionally, the microchannel unit 111 compresses the reaction solution to the bottom of the microfluidic chip 11, so that only the bottom needs to be temperature-controlled, eliminating the nucleic acid reaction tank and the thermal cover in the existing device, making the design of the temperature control device 1 described in the present application more simple and further improving the temperature control rate.
[0056] In an embodiment of the present application, the temperature control device 1 further includes a thermal conductive silicone 15, and the thermal conductive silicone 15 is applied to the heat sink structure 12 and the thermoelectric cooler 13 to improve the heat conduction efficiency.
[0057] In an embodiment of the present application, the microfluidic chip 11 further includes a control unit 112, and the control unit 112 is configured to solve the initial control parameters by using a particle swarm algorithm to perform real-time temperature control on the temperature control device 1. Optionally, the initial control parameters are control parameters of proportional integral derivative (PID) feedback control. The particle swarm optimization (PSO) algorithm is a heuristic optimization algorithm, and particles are iteratively updated based on their own experience and the experience of the group to find the optimal solution.
[0058] In the embodiment of the present application, the PID control parameters and the particle swarm algorithm are integrated to form a comprehensive algorithm, so that the temperature control device 1 has better robustness and adaptability, and has greater practical production value.
[0059] Figure 2 It shows a schematic structural diagram of the control unit described in the embodiment of the present application. As Figure 2 shown, the control unit 112 includes an initialization subunit 1121, a velocity control subunit 1122, an update control subunit 1123, and a result acquisition subunit 1124.
[0060] The initialization subunit 1121 is configured to obtain the initialized particle velocity, individual extreme value, and group extreme value.
[0061] The velocity control subunit 1122 is configured to update the velocity position and calculate the fitness according to the initialized individual extreme value and group extreme value.
[0062] The update control subunit 1123 is configured to update the individual extreme value and the group extreme value of the initialization subunit according to the fitness.
[0063] The result acquisition subunit 1124 is configured to obtain the processed control parameters according to the updated individual extreme value and group extreme value.
[0064] In some possible implementation manners, Figure 3 It shows a schematic flow diagram of the control method described in the embodiment of the present application. As Figure 3As shown, the initial PID parameters are obtained according to the PID control algorithm. In the particle swarm algorithm, the initial particle velocity is obtained according to the initial PID parameters, and the initial individual extreme value and the population extreme value are obtained according to the initial particle velocity. Furthermore, the velocity position is updated according to the initial individual extreme value and the population extreme value, and the fitness is calculated. The individual extreme value and the population extreme value are updated according to the fitness, and it is judged whether the individual extreme value and the population extreme value meet the conditions. If not, the velocity position is updated and the fitness is recalculated. If satisfied, the processed PID control parameters are obtained for MATLAB simulation analysis.
[0065] In some other possible implementation manners, the initial control parameter is K p = 1, K d = 1, K i = 1. After being processed by the particle swarm algorithm, the processed control parameter is K p = 93.9847, K d = 86.1079, K i = 17.3321. Optionally, the above algorithm control can be implemented using STM32 series chips.
[0066] Figure 4 It shows a schematic structural diagram of the heat dissipation structure described in the embodiment of the present application. As Figure 4 shown, the heat dissipation structure 14 is a segmented heat sink. Optionally, the fin thickness of the heat dissipation structure 14 is 2 mm, the fin pitch is 3 mm, and the width of the break notch is 6 mm.
[0067] Figure 5 It shows a schematic structural diagram of the nucleic acid reaction device described in the embodiment of the present application. As Figure 5 shown, the nucleic acid reaction device 2 includes a nucleic acid extraction device 21, a fluorescence detection device 22, and a temperature control device 23.
[0068] The nucleic acid extraction device 21 is used to extract nucleic acid from a sample.
[0069] The fluorescence detection device 22 is used to perform fluorescence detection on the extracted nucleic acid.
[0070] The temperature control device 23 is used to control the temperatures of the nucleic acid extraction device and the fluorescence detection device, and the temperature control device 23 is the temperature control device 1 described in any embodiment of the present application.
[0071] Figure 6 It shows a schematic flow diagram of the temperature control method described in the embodiment of the present application. As Figure 6 shown, the temperature control method includes the following steps S11 to S13.
[0072] Step S11, obtain the initial control parameter.
[0073] Step S12: Solve the initial control parameters using the particle swarm algorithm to obtain the processed control parameters.
[0074] Step S13: Control the nucleic acid reaction conditions and temperature using the processed control parameters.
[0075] In several embodiments provided in the present application, it should be understood that the disclosed system, apparatus or method can be implemented in other ways. For example, the apparatus embodiments described above are merely illustrative. For example, the division of modules / units is only a logical function division. In actual implementation, there may be other division methods. For example, multiple modules or units can be combined or integrated into another system, or some features can be ignored or not executed. Another point is that the displayed or discussed coupling or direct coupling or communication connection to each other can be through some interfaces, and the indirect coupling or communication connection of devices or modules or units can be in electrical, mechanical or other forms.
[0076] The modules / units described as separate components may or may not be physically separated. The components shown as modules / units may or may not be physical modules, that is, they can be located in one place, or they can be distributed to multiple network units. Some or all of the modules / units can be selected according to actual needs to achieve the purpose of the embodiments of the present application. For example, in each embodiment of the present application, the various functional modules / units can be integrated in a processing module, or each module / unit can exist physically alone, or two or more modules / units can be integrated in one module / unit.
[0077] Those of ordinary skill in the art should further realize that the units and algorithm steps of each example described in combination with the embodiments disclosed herein can be implemented by electronic hardware, computer software, or a combination of the two. To clearly illustrate the interchangeability of hardware and software, the composition and steps of each example have been generally described according to functions in the above description. Whether these functions are executed in a hardware or software manner depends on the specific application and design constraints of the technical solution. Professional technicians can use different methods to implement the described functions for each specific application, but such implementation should not be considered to exceed the scope of the present application.
[0078] The embodiments of the present application also provide an electronic device. Figure 7 It shows a schematic structural diagram of the electronic device 700 described in the embodiments of the present application. As Figure 7 shown, in this embodiment, the electronic device 700 includes a memory 710 and a processor 720.
[0079] The memory 710 is used to store computer programs; preferably, the memory 710 includes various media that can store program codes, such as ROM, RAM, magnetic disks, USB flash drives, memory cards, or optical discs.
[0080] Specifically, the memory 710 may include a computer system readable medium in the form of volatile memory, such as random access memory (RAM) and / or cache memory. The electronic device 700 may further include other removable / non-removable, volatile / non-volatile computer system storage media. The memory 710 may include at least one program product having a set (e.g., at least one) of program modules configured to perform the functions of the embodiments of the present application.
[0081] The processor 720 is connected to the memory 710 and is configured to execute the computer program stored in the memory 710, so that the electronic device 700 executes the temperature control method described in an embodiment of the present application.
[0082] Optionally, the processor 720 may be a general-purpose processor, including a central processing unit (CPU), a network processor (NP), etc.; it may also be a digital signal processor (DSP), an application specific integrated circuit (ASIC), a field programmable gate array (FPGA), or other programmable logic devices, discrete gate or transistor logic devices, discrete hardware components.
[0083] Optionally, in this embodiment, the electronic device 700 may further include a display 730. The display 730 is communicatively connected to the memory 710 and the processor 720 and is configured to display a graphical user interface (GUI) interaction interface related to the temperature control method described in the embodiments of the present application.
[0084] An embodiment of the present application also provides a computer-readable storage medium having a computer program stored thereon. When the program is executed by a processor, it implements the temperature control method described in an embodiment of the present application.
[0085] The descriptions of the processes or structures corresponding to the above respective drawings each have their own focuses. For parts not detailed in a certain process or structure, reference may be made to the relevant descriptions of other processes or structures.
[0086] The above embodiments are only illustrative of the principles and effects of the present application and are not intended to limit the present application. Any person familiar with this technology can modify or change the above embodiments without departing from the spirit and scope of the present application. Therefore, all equivalent modifications or changes made by those with ordinary knowledge in the technical field without departing from the spirit and technical idea disclosed in the present application should still be covered by the claims of the present application.
Claims
1. A temperature control device, characterized in that, Comprising: A microfluidic chip for controlling nucleic acid reaction conditions; A heat sink structure for heat transfer of the nucleic acid reaction; A thermoelectric cooler for adjusting the temperature of the nucleic acid reaction; A heat dissipation structure for dissipating heat from the nucleic acid reaction.
2. The temperature control device according to claim 1, wherein, The microfluidic chip includes a microchannel unit for compressing the reaction solution to the bottom of the microfluidic chip.
3. The temperature control device according to claim 1, characterized in that, Also included is thermal conductive silicone, which is applied to the heat sink structure and the thermoelectric cooler to improve the heat conduction efficiency.
4. The temperature control device according to claim 1, characterized in that, The microfluidic chip further includes a control unit for solving initial control parameters using a particle swarm algorithm to perform real-time temperature control of the temperature control device.
5. The temperature control device according to claim 4, characterized in that, The control unit includes: An initialization subunit for obtaining initial particle velocities, individual extrema, and global extrema; A velocity control subunit for updating the velocity position and calculating the fitness according to the initialized individual extrema and global extrema; An update control subunit for updating the individual extrema and the global extrema of the initialization subunit according to the fitness; A result subunit for obtaining the processed control parameters according to the updated individual extrema and global extrema.
6. The temperature control device according to claim 1, characterized in that The heat dissipation structure is a segmented heat sink.
7. A nucleic acid reaction device, characterized in that, Comprising: A nucleic acid extraction device for extracting nucleic acid from a sample; A fluorescence detection device for performing fluorescence detection on the extracted nucleic acid; A temperature control device for controlling the temperatures of the nucleic acid extraction device and the fluorescence detection device, and the temperature control device is the temperature control device according to any one of claims 1 to 6.
8. A temperature control method, characterized in that, Comprising: Obtaining initial control parameters; Solving the initial control parameters using a particle swarm algorithm to obtain processed control parameters; Controlling nucleic acid reaction conditions and temperature using the processed control parameters.
9. An electronic device, characterized in that, The electronic device includes: A memory for storing a computer program; A processor for executing the computer program stored in the memory so that the electronic device executes the temperature control method according to claim 8.
10. A computer-readable storage medium having a computer program stored thereon, characterized in that, When the program is executed by the processor, it implements the temperature control method according to claim 8.