Detection system
By designing a detection system containing a probe module embedded in the outer wall of the reaction tube and an adapter tube, the existing equipment has solved the problems of difficulty in real-time monitoring and complex operation in rapid on-site detection, and achieved rapid and accurate nucleic acid amplification and detection.
Patent Information
- Application Number
- CN202510185431.8
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-02-20
- Publication Date
- 2025-05-02
- Estimated Expiration
- 2045-02-20
Smart Images

Figure CN119913037A_ABST
Abstract
Description
Technical Field
[0001] The present disclosure relates to the technical field of biochemistry and medical detection, and more specifically, to a detection system. Background Art
[0002] In the field of molecular biology and clinical diagnosis, although technologies such as polymerase chain reaction (PCR) and loop-mediated isothermal amplification (LAMP) have been widely used in many fields such as pathogen detection, genetic disease diagnosis, forensics and food safety, they still face challenges in their application in rapid on-site detection and resource-limited environments.
[0003] At present, the nucleic acid amplification and detection processes are usually separated, resulting in the inability to achieve real-time monitoring. In addition, after the completion of nucleic acid amplification, the lid needs to be opened to extract samples for testing. This process not only increases the complexity of the operation, but also easily generates aerosol pollution, affecting the accuracy of the results. In order to achieve efficient temperature cycle control, the heat conduction components in existing equipment usually use large aluminum blocks, which occupy a large space, making the overall size of the equipment bulky and heavy, and the heating and cooling speed is slow, which is not conducive to rapid on-site detection and portable applications. At the same time, most of the temperature sensors of existing portable devices do not directly contact the reaction liquid, and there are errors in the liquid temperature sensing. When the ambient temperature difference is large, the temperature control is inaccurate.
[0004] In addition, a heat conduction structure currently used for PCR temperature control, which connects the heat sink under the sample piece through a graphene heat conduction pad, improves the heat conduction efficiency, but the heat sink is large in size and weight, making it inconvenient to carry. And a system for generating a thermal gradient in a channel, which achieves temperature control by setting a nucleic acid denaturation zone, a nucleic acid annealing zone, and a nucleic acid polymerization zone, but this system requires a solenoid valve or a mechanical switch, and the device is complex and not easy to carry. After completing the PCR temperature cycle, the reaction solution needs to be extracted to test the nucleic acid concentration, which is not easy to detect immediately and is prone to aerosol contamination. Summary of the invention
[0005] In view of this, the present disclosure provides a detection system, including: at least one reaction module, each reaction module includes a reaction tube, a resistance wire and a reaction tube cover, wherein the outer wall of the reaction tube is provided with a groove with a preset pitch, the resistance wire is embedded in the outer wall of the reaction tube through the groove, and the reaction tube cover is provided with a through hole; the resistance wire is used to heat the target analyte according to a preset temperature cycle period to cause the target analyte to undergo an amplification reaction; at least one probe module, one probe module is inserted into a reaction tube through the through hole, and one probe module is used to detect the electrochemical signal of the target analyte.
[0006] According to an embodiment of the present disclosure, the diameter of the resistance wire is less than or equal to 1 mm.
[0007] According to an embodiment of the present disclosure, the shape ratio of the resistance wire is a, 1≦a≦5; wherein the shape ratio is the ratio of the first pitch to the second pitch; along the direction from the reaction tube cover to the bottom of the reaction tube, the first pitch is the first pitch close to the bottom of the reaction tube, and the second pitch is the first pitch close to the reaction tube cover.
[0008] According to an embodiment of the present disclosure, it also includes: at least one temperature sensor, a temperature sensor is arranged on a probe module or a reaction module, and the temperature sensor is used to detect the temperature of the target object to be tested.
[0009] According to an embodiment of the present disclosure, it further includes: at least one preprocessing module, one preprocessing module is connected to a reaction module, and is used to preprocess the initial sample to extract the target analyte, and input the target analyte into the reaction module.
[0010] According to an embodiment of the present disclosure, when a probe module is used to detect an electrochemical signal of a target object to be detected, the probe module includes an electrochemical electrode.
[0011] According to an embodiment of the present disclosure, when a temperature sensor is disposed on a probe module, the electrochemical electrode is disposed on a first surface of the probe module, and the temperature sensor is disposed on a second surface of the probe module, wherein the first surface and the second surface are opposite to each other.
[0012] According to an embodiment of the present disclosure, the reaction tube further includes a fluorescent dye probe, a molecular dye probe or a specific fluorescent probe for fluorescence detection; and / or, the reaction tube further includes a colorimetric substance for colorimetric detection.
[0013] According to an embodiment of the present disclosure, it also includes: a heat dissipation module for adjusting the temperature of the reaction tube module.
[0014] According to an embodiment of the present disclosure, it also includes: a temperature control circuit module, which is used to adjust the working state of the resistance wire and the working state of the heat dissipation module according to the feedback temperature of the temperature sensor.
[0015] The detection system provided by the embodiments of the present disclosure has at least the following beneficial effects:
[0016] By arranging a three-dimensionally wound resistance wire on the outer wall of the reaction tube, rapid three-dimensional heating of the reaction tube can be achieved. At the same time, the optimization of the shape ratio of the resistance wire ensures the uniform and rapid change of the temperature in the reaction tube, effectively improving the cycle speed of the PCR reaction, while reducing the overall volume of the device, which is convenient for on-site detection.
[0017] The probe module is inserted into the reaction tube through the through hole on the reaction tube cover and is sealed and bonded to the reaction tube, thereby realizing instant detection of the target object to be tested in a closed space and avoiding aerosol contamination caused by the extraction of reactants when detecting electrochemical signals, which affects the detection accuracy and the speed of instant response.
[0018] At the same time, by arranging a temperature sensor on the probe module to be in direct contact with the reaction liquid, the accuracy of temperature detection is effectively improved and the speed of real-time temperature response is increased. BRIEF DESCRIPTION OF THE DRAWINGS
[0019] The above and other objects, features and advantages of the present disclosure will become more apparent through the following description of the embodiments of the present disclosure with reference to the accompanying drawings, in which:
[0020] Figure 1 The schematic diagram of the structure of the reaction module and the probe module of the embodiment of the present disclosure is shown schematically;
[0021] Figure 2 A schematic diagram of a structure in which the shape ratio of a resistance wire according to an embodiment of the present disclosure is 1 is shown;
[0022] Figure 3 A schematic diagram of a structure in which the shape ratio of a resistance wire is 2 according to an embodiment of the present disclosure is shown;
[0023] Figure 4 Schematic diagrams of temperature sensors in four modes according to embodiments of the present disclosure are schematically shown;
[0024] Figure 5 A schematic diagram schematically shows the connection of a preprocessing module according to an embodiment of the present disclosure;
[0025] Figure 6 A schematic diagram of a preprocessing module according to an embodiment of the present disclosure is schematically shown;
[0026] Figure 7 A schematic diagram of a probe module according to an embodiment of the present disclosure is schematically shown;
[0027] Figure 8 A schematic diagram of a heat dissipation module according to an embodiment of the present disclosure is schematically shown;
[0028] Fig. 9 The device diagram of the detection system according to the embodiment of the present disclosure is schematically shown. DETAILED DESCRIPTION
[0029] Hereinafter, embodiments of the present disclosure will be described with reference to the accompanying drawings. However, it should be understood that these descriptions are exemplary only and are not intended to limit the scope of the present disclosure. In the following detailed description, for ease of explanation, many specific details are set forth to provide a comprehensive understanding of the embodiments of the present disclosure. However, it is apparent that one or more embodiments may also be implemented without these specific details. In addition, in the following description, descriptions of known systems and technologies are omitted to avoid unnecessary confusion of the concepts of the present disclosure.
[0030] The terms used herein are only for describing specific embodiments and are not intended to limit the present disclosure. The terms "comprise", "include", etc. used herein indicate the existence of features, steps, operations and / or components, but do not exclude the existence or addition of one or more other features, steps, operations or components.
[0031] All terms (including technical and scientific terms) used herein have the meanings commonly understood by those skilled in the art unless otherwise defined. It should be noted that the terms used herein should be interpreted as having a meaning consistent with the context of this specification and should not be interpreted in an idealized or overly rigid manner.
[0032] When using expressions such as "at least one of A, B, and C, etc.", they should generally be interpreted according to the meaning of the expression commonly understood by those skilled in the art (for example, "a system having at least one of A, B, and C" should include but is not limited to a system having A alone, B alone, C alone, A and B, A and C, B and C, and / or A, B, C, etc.).
[0033] Traditional nucleic acid amplification equipment is bulky, expensive, and requires complex operation and maintenance, which limits its application in remote areas or on-site testing. At the same time, laboratory diagnostic methods usually take several days, which often leads to missing the best time for treatment and failing to provide patients with timely and effective drug options.
[0034] When PCR technology first appeared, temperature control usually required manual transfer between water baths of different temperatures. With the development of automated instruments, PCR temperature control has gradually adopted technologies such as mechanical transfer, water baths, air circulation, thermoelectric coolers (TECs), and microfluidics. Current commercial instruments use large aluminum blocks attached to the wall for temperature control. Due to their large size and slow heating and cooling speed, and the determination of the initial target gene concentration by fluorescence intensity, large instruments such as fluorescence microscopes are required. Samples are usually transported to the laboratory for testing, which requires a long waiting time.
[0035] As the application of portable rapid PCR instruments in scenarios such as on-site testing and emergency response increases, these instruments need to meet requirements such as small size, light weight, low power consumption, fast operation speed, wide adaptability, and easy operation. In addition, real-time monitoring of temperature changes and nucleic acid signals during the reaction process is crucial to improving the accuracy and efficiency of detection, but existing technologies often find it difficult to achieve this.
[0036] For example, a heat conduction structure currently used for PCR temperature control connects a heat sink to the sample through a graphene heat conduction pad. Although this improves the heat conduction efficiency, the heat sink is large in size and weight, making it inconvenient to carry. Another example is that temperature control is achieved by setting up a nucleic acid denaturation zone, a nucleic acid annealing zone, and a nucleic acid polymerization zone. However, this system requires a solenoid valve or a mechanical switch, which is complex and not easy to carry. After the PCR temperature cycle is completed, the reaction solution needs to be extracted to test the nucleic acid concentration, which is not easy to detect immediately and is prone to aerosol contamination.
[0037] Based on this, the embodiments of the present disclosure provide a detection system that can meet the needs of different biochemical experiments for precise temperature control, thereby providing more reliable results in the fields of molecular diagnosis, pathogen detection, gene expression analysis, etc. At the same time, this embodiment has the advantages of being small and portable, easy to operate, cost-effective, fast in response, wide in scope of application, and strong in scalability, so that it has a wide range of application potential in on-site rapid detection outside the laboratory.
[0038] Figure 1 The schematic diagram shows the structures of the reaction module and the probe module of the embodiment of the present disclosure.
[0039] like Figure 1 As shown, the present disclosure provides a detection system, including: at least one reaction module 100 and at least one probe module 110 .
[0040] Each reaction module includes a reaction tube 101, a resistance wire 103 and a reaction tube cover 102, wherein the outer wall of the reaction tube 101 is provided with a groove with a preset pitch, the resistance wire 103 is embedded in the outer wall of the reaction tube through the groove, and the reaction tube cover 102 is provided with a through hole; the resistance wire is used to heat the target analyte according to a preset temperature cycle period to cause the target analyte to undergo an amplification reaction.
[0041] At least one probe module 110 is inserted into one reaction tube 101 through a through hole, and one probe module 110 is used to detect the electrochemical signal of the target object to be tested.
[0042] In the embodiment of the present disclosure, the resistance wire 103 is three-dimensionally wound around the reaction tube through a groove with a preset pitch on the outer wall of the reaction tube 101. By heating the resistance wire 103, the reaction tube 101 can be heated three-dimensionally, ensuring a rapid change in the temperature in the reaction tube, increasing the cycle speed of the PCR reaction, and reducing the overall volume of the device, which is convenient for on-site detection.
[0043] The reaction tube cover 102 is threadedly connected to the reaction tube 101, and the probe module 110 is inserted into the reaction tube 101 through a through hole provided on the reaction tube cover 102, and is sealed and bonded to the reaction tube 101, wherein the specifications of the probe module and the specifications of the reaction module match each other. The instant detection of the target object to be tested in a confined space is realized, and the need to extract reactants to cause aerosol contamination during the traditional detection of electrochemical signals is avoided, thereby affecting the accuracy of the detection and the speed of the instant response. At the same time, the process is simplified, which is suitable for rapid on-site detection and emergency response. In addition, the disposable nature of the reaction tube and the probe ensures the sterility and portability during the detection process and avoids the risk of cross contamination.
[0044] Based on the above embodiment, the reaction tube 101 can be prepared by injection molding or laser engraving, but is not limited thereto. The material of the reaction tube can include high temperature resistant plastic or ceramic, but is not limited thereto.
[0045] The material of the resistance wire 103 may include iron, alloy, etc. to improve the heating efficiency, but is not limited thereto.
[0046] Based on the above embodiment, the diameter of the resistance wire 103 is less than or equal to 1 mm.
[0047] In the embodiment of the present disclosure, by controlling the diameter of the resistance wire 103 to be no greater than 1 mm, it is possible to achieve uniform temperature increase of the target analyte solution in the reaction tube 101 and improve energy utilization.
[0048] Figure 2 A schematic diagram of a structure in which the shape ratio of a resistance wire is 1 according to an embodiment of the present disclosure is shown schematically.
[0049] Figure 3 A schematic diagram of a structure in which the resistance wire shape ratio is 2 according to an embodiment of the present disclosure is shown schematically.
[0050] Based on the above embodiment, the shape ratio of the resistance wire is a, 1≦a≦5; wherein the shape ratio is the ratio of the first pitch to the second pitch; along the direction from the reaction tube cover to the reaction tube bottom, the first pitch is the first pitch close to the reaction tube bottom, and the second pitch is the first pitch close to the reaction tube cover.
[0051] For example, Figure 2The figure shows a schematic diagram of a resistance wire with a shape ratio of 1 and a temperature distribution diagram, which shows the temperature variation of the resistance wire at different positions. As can be seen from the figure, the temperature in some areas is higher, while the temperature in other areas is lower, indicating that the resistance wire has a relatively uneven temperature problem during the heating process.
[0052] like Figure 3 The figure shows a schematic diagram and temperature distribution diagram of a resistance wire with a shape ratio of 2. From this figure, it can be seen that the temperature distribution is uniform in the entire area. By adjusting the pitch of the resistance wire, the temperature of the entire reaction tube can be adjusted, which helps to uniformly heat the reaction tube. Compared with the resistance wire with a shape ratio of 1, the resistance wire with a shape ratio of 2 has a more uniform temperature distribution and is easier to achieve uniform heating of the reaction tube.
[0053] In the embodiment of the present disclosure, the pitch of the resistance wire is adjusted to match the heating speed of the upper and lower parts of the reaction tube to achieve uniform heating of the entire system, wherein the pitch is adjusted from the first pitch to the second pitch in a gradually decreasing manner.
[0054] Figure 4 Schematic diagrams of temperature sensors in four modes according to embodiments of the present disclosure are schematically shown.
[0055] like Figure 4 As shown, according to an embodiment of the present disclosure, it also includes: at least one temperature sensor, a temperature sensor is arranged on a probe module 110 or a reaction module 100, and the temperature sensor is used to detect the temperature of the target object to be tested.
[0056] like Figure 4 As shown in Figure a, when a temperature sensor is set on a reaction module, the resistance wire can also be the temperature sensor 104, that is, the resistance wire not only heats the reaction tube, but also has the function of a temperature sensing resistor, and can monitor the temperature change of the reaction system in real time. This integrated structural design can simplify the system structure.
[0057] You can Figure 4 As shown in FIG. b, when a temperature sensor is arranged on a reaction module, the temperature sensor 105 is embedded in the bottom of the reaction tube, and the temperature is controlled by this arrangement.
[0058] You can Figure 4 As shown in Figure c, non-contact temperature measurement, such as infrared thermal imaging technology, is used to remotely detect the temperature of the reaction system through infrared thermal imaging equipment 106. This temperature measurement method does not require direct contact with the reaction system, thus avoiding possible contamination risks.
[0059] You can Figure 4As shown in Figure d, the temperature sensor is set on the probe module, penetrated into the solution, and directly measures the temperature of the reaction system. This can achieve accurate measurement, perform precise temperature control, and improve temperature control efficiency.
[0060] In the embodiments of the present disclosure, by setting the above different configurations, the temperature control requirements of the portable ultrafast PCR device in different application scenarios can be met. The temperature sensing module in the present embodiment can be a thermistor or a thermocouple, but is not limited thereto.
[0061] Figure 5 A schematic diagram schematically shows the connection of a preprocessing module according to an embodiment of the present disclosure.
[0062] Figure 6 A schematic diagram of a preprocessing module according to an embodiment of the present disclosure is schematically shown.
[0063] like Figure 5 As shown, according to an embodiment of the present disclosure, it also includes: at least one preprocessing module, a preprocessing module 140 is connected to a reaction module 100, and is used to preprocess the initial sample to extract the target analyte, and input the target analyte into the reaction module.
[0064] For example, the initial sample can be pretreated by magnetic bead adsorption elution method, concentrated salt method or column method.
[0065] In the embodiments of the present disclosure, a pretreatment module can be integrated on the reaction tube as needed, so that the target analyte can be directly and efficiently extracted. For example, a channel can be set on the reaction tube cover, so that the pretreatment module is connected to the reaction tube through this channel to flow the pretreated initial sample into the reaction tube. Integrated and efficient extraction, amplification, and detection are achieved, the integration of the detection system is improved, and the response speed is accelerated.
[0066] According to an embodiment of the present disclosure, the pre-processing module 140 can be prepared by machining or injection molding. Meanwhile, the sealing method includes but is not limited to a rubber plug, a silicone plug or aluminum foil.
[0067] like Figure 6 As shown, the pretreatment module 140 includes a liquid quantitative module and a nucleic acid extraction module. The liquid quantitative module includes a rubber stopper 141, a stopper 142 and a polypropylene tube 143.
[0068] The rubber stopper 141 is fixed on the stopper 142 to achieve the sealing of the pretreatment module. The stopper 142 is used to control and limit the position of the rubber stopper 141 to ensure the accuracy during the extraction process. The polypropylene tube 143 matches the specifications of the rubber stopper 141 and connects the stopper 142 and the rubber stopper 141 to form a channel for liquid flow.
[0069] The nucleic acid extraction module 144 includes magnetic beads, a lysate 145, a washing solution 146 and an elution solution 147. Under the influence of the magnetic field, the magnetic beads move into the lysate 145 to enrich nucleic acids, are washed in the washing solution 146 through a small channel 148, and then are eluted in the elution solution 147 through a small channel 148.
[0070] In the embodiments of the present disclosure, the preprocessing module can quickly, efficiently and automatically complete the nucleic acid extraction process to support subsequent PCR detection.
[0071] Figure 7 A schematic diagram of a probe module according to an embodiment of the present disclosure is schematically shown.
[0072] like Figure 7 As shown, according to an embodiment of the present disclosure, when a probe module is used to detect an electrochemical signal of a target object to be detected, the probe module 110 includes an electrochemical electrode 111 .
[0073] For example, in the temperature cycle stage, when the temperature is fixed, the electrochemical detection can be started once every 5 cycles when the temperature drops to 65°C. The detected electrochemical signal is transmitted to the external device through a wireless or wired transmission module, wherein the wireless transmission module can adopt Bluetooth, WiFi, RFID or NFC, etc.
[0074] The electrochemical electrodes may be three electrodes, and the configuration of the three electrodes includes but is not limited to interdigitated electrodes, circular electrodes or simplified two electrodes to meet different electrochemical detection requirements.
[0075] On the basis of the above embodiment, in the case where a temperature sensor is arranged on a probe module, the electrochemical electrode 111 is arranged on the first surface of the probe module, and the temperature sensor 112 is arranged on the second surface of the probe module, wherein the first surface and the second surface are opposite to each other. The temperature of the reaction liquid and the chemical signal of the reaction liquid can be detected in real time.
[0076] The probe module 110 further includes an insulating layer 113. In the inactive area of the probe module, the insulating layer 113 is prepared by coating a non-conductive material to achieve electrical isolation and avoid electrical interference. The probe module can be prepared by a screen printing process, but is not limited thereto, which can ensure accurate layout of the electrodes and excellent electrochemical performance.
[0077] At the same time, the connection of the electrochemical electrodes of the probe module 110 can adopt a plug-and-play interface. The universal contact 114 can be formed by setting a through hole on the first surface and the second surface or through the tail end of the probe module. The probe module can be quickly and stably connected to the universal connector, and the specification design of the universal contact 114 conforms to the connector specification of the industry standard, ensuring compatibility with existing equipment and easy integration.
[0078] For example, the electrochemical electrode 111 is in contact with the reaction system of the target substance to be detected, and an electrochemical detection method is used to scan at a fixed temperature during the temperature cycle to obtain an electrochemical signal. The electrochemical detection method includes but is not limited to square wave voltammetry, differential pulse voltammetry, and electrochemical impedance spectroscopy.
[0079] In the embodiment of the present disclosure, after the probe module 110 is properly immersed, the reaction tube cover of the reaction module is tightly closed to maintain the sterile environment of the reaction system and prevent any external contamination, thereby ensuring that the temperature sensor 112 can accurately monitor the temperature change of the reaction system and the electrochemical electrode 111 can perform effective electrochemical signal detection.
[0080] According to an embodiment of the present disclosure, the reaction tube further includes a fluorescent dye probe, a molecular dye probe or a specific fluorescent probe for fluorescence detection; and / or, the reaction tube further includes a colorimetric substance for colorimetric detection.
[0081] In the embodiments of the present disclosure, the fluorescence intensity of the target object to be detected can also be detected. Specifically, a fluorescent dye probe, a molecular dye probe or a specific fluorescent probe is added to the reaction tube, and these probes can specifically bind to the target nucleic acid sequence during the PCR reaction, and generate a detectable fluorescent signal after binding. At this time, the fluorescent signal generated is linearly related to the concentration of the target nucleic acid sequence, and the concentration of the target nucleic acid sequence can be quantitatively analyzed by detecting the intensity of the above-mentioned fluorescent signal.
[0082] For example, the temperature cycle adopts a "two-step method", such as the high temperature zone is 92℃-95℃, and the low temperature zone is 52℃-60℃. Use nuclease-free water to gradually dilute the nucleic acid plasmid of known concentration to prepare a series of dilutions ranging from 1copy / uL-1000copy / uL, configure 20uL reaction system components, and prepare samples with different gradient concentrations. And place the samples of different gradient concentrations in the reaction module for PCR amplification reaction. The results of the above operation show that 40 PCR cycles can be completed within 10 minutes, and the minimum detection limit can be 1copy / uL of nucleic acid. Efficient fluorescent PCR amplification can be achieved in a short time, and it has the ability to detect low-concentration nucleic acids.
[0083] Based on the above embodiments, the color developing substance may include organic color developing agents, inorganic color developing agents, metal complexes and nano materials, but is not limited thereto.
[0084] In the embodiments of the present disclosure, colorimetric detection can also be performed. Specifically, organic color developers, inorganic color developers, metal complexes, nanomaterials, etc. are added to the reaction tube, and these substances can bind to the modification groups during the PCR reaction and produce detectable color changes after binding. The color changes produced at this time are positively correlated with the concentration of the target nucleic acid sequence, and the concentration of the target nucleic acid sequence can be analyzed by detecting the intensity of the above color changes.
[0085] At the same time, according to actual detection needs, at least one detection method among electrochemical detection, fluorescence detection and colorimetric detection can be selected to detect the target object to be detected. For example, during detection, the electrochemical electrode can be energized to make the electrochemical electrode enter a working state, and the target object to be detected can be subjected to electrochemical detection. Fluorescence intensity detection and / or colorimetric detection can be performed on the target object to be detected. During detection, the electrochemical electrode is not energized to make the electrochemical electrode not enter a working state, and any of the above detection probes and / or colorimetric substances are added to the reaction tube to detect the fluorescence and / or color of the reaction solution. Electrochemical detection, fluorescence intensity detection and colorimetric detection can also be performed on the target object to be detected at the same time, that is, the electrochemical electrode is energized to make it undergo electrochemical detection, and any of the above probes and colorimetric substances can be added to perform optical detection. The detection system of the present embodiment can be adapted to a variety of real-time detection methods, which can be used independently or in combination.
[0086] In some possible embodiments, by integrating a pretreatment module on the reaction module and setting a temperature sensor on the probe module, efficient extraction, amplification and detection integration can be completed within 15 minutes, and is applicable to a volume range of 5 μL to 500 μL.
[0087] Figure 8 A schematic diagram of a heat dissipation module according to an embodiment of the present disclosure is schematically shown.
[0088] like Figure 8 As shown, according to an embodiment of the present disclosure, it further includes: a heat dissipation module 120 for adjusting the temperature of the reaction tube module. The heat dissipation module 120 may be a fan.
[0089] On the basis of the above embodiment, it further includes: a temperature control circuit module 200, which is used to adjust the working state of the resistance wire and the working state of the heat dissipation module according to the feedback temperature of the temperature sensor.
[0090] The reaction module 100 is fixed on the tube rack 130 and close to the fan 120. By setting the temperature control circuit module 200 to receive the temperature signal fed back by the temperature sensor 112 and adjusting the working state of the resistance wire 103 and the fan 120 according to the fed back temperature signal, the current of the resistance wire 103 or the fan 120 can be accurately controlled. At the same time, the temperature control circuit module 200 is provided with a proportional-integral-derivative (PID) adjustment algorithm, which can calculate the necessary control action according to the deviation between the real-time temperature and the preset temperature to maintain the PCR reaction system within a precise temperature range.
[0091] For example, when it is detected that the actual temperature is significantly lower than the preset high temperature range, such as 92°C-95°C, the PID temperature control circuit will instruct the resistor to operate at a higher power to quickly raise the system temperature to the target range. On the contrary, when the actual temperature is only slightly lower than the set temperature, the heating power will be adjusted to a lower level to achieve fine-tuning control of the temperature. In addition, when the actual temperature of the system exceeds the set high temperature range, the temperature control circuit module will start the fan to assist in heat dissipation and adjust the temperature set point to a lower range, such as 52°C-58°C, to keep the system running stably within this temperature range. Accordingly, when the actual temperature drops below the set low temperature range, the fan 120 will be turned off, and the PID temperature control circuit will readjust the temperature set point to a high temperature range, such as 92°C-95°C, to maintain the system at the required high temperature for reaction.
[0092] In the embodiments of the present disclosure, the temperature control circuit module can accurately obtain the temperature feedback of the reaction tube, and then can accurately regulate the temperature rise or fall to meet the temperature cycle conditions of PCR. Compared with the traditional reaction tube without temperature control function, the present embodiment can be widely used in various biochemical reaction scenarios that require precise temperature control. For example, in addition to PCR reactions, the temperature control device is also suitable for reaction scenarios that require precise temperature control, such as LAMP, recombinase polymerase amplification (RPA for short).
[0093] According to an embodiment of the present disclosure, the temperature control circuit module may adopt an STM32 single-chip microcomputer or a Raspberry Pi microcontroller.
[0094] Fig. 9 The device diagram of the detection system according to the embodiment of the present disclosure is schematically shown.
[0095] The detection system further comprises a signal display module 300 for displaying the feedback temperature and electrochemical signal of the temperature sensor.
[0096] The power module 400 is used to provide power to the entire detection system to ensure that each module can operate normally.
[0097] During assembly, after integrating multiple reaction modules 100, multiple probe modules 110 and multiple pretreatment modules 140, they are fixed in the center of the housing 500 through the tube rack 130. One of the reaction modules 100 integrates a probe module 110 and a pretreatment module 140. The fan 120 is arranged on one side of the device near the reaction module 100, so as to quickly reduce the temperature in the reaction tube 101 when needed and realize rapid temperature regulation. The temperature control circuit module is arranged near the bottom of the reaction tube and is electrically connected to the temperature sensor, so as to accurately control the working state of the resistance wire 103 and the fan 120. The signal display module 300 is arranged on the top of the housing 500, so as to intuitively display the reaction state. The power supply module 400 is arranged inside the housing 500. By arranging the entire device in the housing, the entire device can remain stable under various environments. And this integrated design not only improves the efficiency and accuracy of molecular diagnosis, but also has broad application prospects and market potential.
[0098] It will be appreciated by those skilled in the art that the features described in the various embodiments and / or claims of the present disclosure may be combined and / or combined in a variety of ways, even if such combinations and / or combinations are not explicitly described in the present disclosure. In particular, the features described in the various embodiments and / or claims of the present disclosure may be combined and / or combined in a variety of ways without departing from the spirit and teachings of the present disclosure. All of these combinations and / or combinations fall within the scope of the present disclosure.
[0099] The embodiments of the present disclosure are described above. However, these embodiments are only for illustrative purposes and are not intended to limit the scope of the present disclosure. Although the embodiments are described above separately, this does not mean that the measures in the various embodiments cannot be used in combination to advantage. The scope of the present disclosure is defined by the attached claims and their equivalents. Without departing from the scope of the present disclosure, those skilled in the art may make a variety of substitutions and modifications, which should all fall within the scope of the present disclosure.
Claims
1. A detection system, characterized in that: include: At least one reaction module, each reaction module comprises a reaction tube, a resistance wire and a reaction tube cover, wherein the outer wall of the reaction tube is provided with a groove with a preset pitch, the resistance wire is embedded in the outer wall of the reaction tube through the groove, and the reaction tube cover is provided with a through hole; the resistance wire is used to heat the target analyte according to a preset temperature cycle period to cause the target analyte to undergo an amplification reaction; At least one probe module is inserted into a reaction tube through the through hole, and the probe module is used to detect the electrochemical signal of the target object to be tested.
2. The detection system according to claim 1, characterized in that: The diameter of the resistance wire is less than or equal to 1 mm.
3. The detection system according to claim 2, characterized in that: The shape ratio of the resistance wire is a, 1≦a≦5; Wherein, the shape ratio is the ratio of the first pitch to the second pitch; Along the direction from the reaction tube cover to the reaction tube bottom, the first pitch is the first pitch close to the reaction tube bottom, and the second pitch is the first pitch close to the reaction tube cover.
4. The detection system according to claim 1, characterized in that: Also includes: At least one temperature sensor, one temperature sensor is arranged on the one probe module or the one reaction module, and the temperature sensor is used to detect the temperature of the target object to be detected.
5. The detection system according to claim 4, characterized in that: Also includes: At least one pre-processing module, one pre-processing module is connected to one reaction module, and is used to pre-process the initial sample to extract the target analyte, and input the target analyte into the reaction module.
6. The detection system according to claim 4, characterized in that: In the case where the one probe module is used to detect the electrochemical signal of the target object to be detected, the probe module includes an electrochemical electrode.
7. The detection system according to claim 6, characterized in that: In the case where the one temperature sensor is disposed on the one probe module, the electrochemical electrode is disposed on a first surface of the probe module, and the temperature sensor is disposed on a second surface of the probe module, wherein the first surface and the second surface are opposite to each other.
8. The detection system according to claim 1, characterized in that: The reaction tube also includes a fluorescent dye probe, a molecular dye probe or a specific fluorescent probe for fluorescence detection; And / or, the reaction tube further comprises a color developing substance for colorimetric detection.
9. The detection system according to claim 4, characterized in that: Also includes: The heat dissipation module is used to adjust the temperature of the reaction tube module.
10. The detection system according to claim 9, characterized in that: Also includes: The temperature control circuit module is used to adjust the working state of the resistance wire and the working state of the heat dissipation module according to the feedback temperature of the temperature sensor.
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