Refrigeration control module and method and gene sequencing pretreatment system

Abstract

The invention provides a refrigeration control module and a gene sequencing pretreatment system, and relates to the technical field of gene sequencing pretreatment, and the refrigeration control module comprises a temperature control unit, and a reagent plate position, a temperature adjusting part and a heat dissipation part which are sequentially arranged from top to bottom, the temperature control unit comprises a temperature control assembly and two temperature sensors connected with the temperature control assembly, the two temperature sensors are connected with the reagent plate position and the heat dissipation part respectively, and the temperature control assembly controls the temperature of the reagent plate position and the temperature of the heat dissipation part according to the temperature information of the reagent plate position and the temperature information of the heat dissipation part fed back by the temperature sensors. And the temperature adjusting part or the temperature adjusting part and the heat dissipation part is adjusted and controlled, so that the temperature of the reagent plate position reaches a set range. According to the technical scheme, the technical problem of efficient cooling of a refrigeration control module in the prior art is solved.

Description

Technical Field

[0001] This application relates to the technical field of pre-treatment for gene sequencing, particularly to a refrigeration control module and a pre-treatment system for gene sequencing. Background Art

[0002] The refrigeration control module is a common small module for reagent storage, mainly used to hold and store reagent plate positions, so as to control the reagent temperature between 4°C and 8°C to ensure a good storage environment for the reagent. The refrigeration control module is mainly applied to the storage function of medical instrument reagents. Since the whole process of the instrument is fully automated and the time for other processes in the experiment is relatively long, in order to ensure that the reagents in this plate position do not affect the experiment during operation, they are stored at a low temperature during other operations. Due to space limitations and noise reduction, the size of the heat dissipation fins is small and the air volume of the fan is small, which cannot ensure that the Peltier can maintain the optimal energy efficiency in any case, and sometimes cannot reach the specified temperature, thus unable to provide a good low-temperature storage environment. Summary of the Invention

[0003] This application provides a refrigeration control module and a pre-treatment system for gene sequencing to solve the technical problem of how to efficiently cool the refrigeration control module in the prior art. The preferred technical solutions provided in this application can produce many technical effects, which will be elaborated below.

[0004] To achieve the above object, on the one hand, this application provides a refrigeration control module, including: a temperature control unit, and a reagent plate position, a temperature adjustment component, and a heat dissipation component arranged in sequence from top to bottom. The temperature control unit includes a temperature control component and a temperature sensor connected to the temperature control component. Two temperature sensors are provided, which are respectively connected to the reagent plate position and the heat dissipation component. The temperature control component adjusts the temperature adjustment component or the temperature adjustment component and the heat dissipation component according to the reagent plate position temperature information and the heat dissipation component temperature information fed back by the temperature sensor, so that the temperature of the reagent plate position reaches the set range.

[0005] Optionally, the temperature control component is respectively connected to the temperature sensor through an ADC (Analog-to-Digital Sampling) sampling circuit.

[0006] Optionally, the temperature adjustment component is set as a Peltier, and the heat dissipation component includes heat dissipation fins, and the Peltier is arranged on the heat dissipation fins.

[0007] Optionally, the heat dissipation component further includes a fan, the fan is arranged below the heat dissipation fins, and the heat dissipation component temperature information is the heat dissipation fin temperature information.

[0008] Optionally, a heat insulation plate is provided between the heat dissipation fins and the reagent plate position. A through groove is provided in the middle of the heat insulation plate, and the Peltier is located in the through groove.

[0009] Optionally, the temperature control component is arranged on the control board, and the control board is arranged below the heat dissipation component.

[0010] Optionally, the temperature control component includes a controller, a single-pole double-throw analog switch, a MOS (Metal-Oxide-Semiconductor) transistor driver chip, a MOS transistor, and a thermoelectric cooler (TEC) connected in sequence. The controller leads out two signal pins, both of which are respectively connected to the two single-pole double-throw analog switches. The two single-pole double-throw analog switches are respectively connected to a MOS transistor driver chip. Each MOS transistor driver chip is connected to a group of MOS transistors, and the output ends of the two groups of MOS transistors are respectively connected to the TEC.

[0011] Optionally, the two signal pins of the controller include a PWM (Pulse Width Modulation) signal pin and a high-low level pin, and the PWM signal pin is connected to different pins of the two single-pole double-throw analog switches.

[0012] Optionally, it further includes a communication control module, and the communication control module is respectively connected to the central control module and the temperature control unit.

[0013] On the other hand, the present application provides a refrigeration control method for any one of the refrigeration control modules described above, including:

[0014] Obtaining the temperature information of the reagent plate position and the temperature information of the heat dissipation component through a temperature sensor;

[0015] Controlling the temperature adjustment component or controlling the temperature adjustment component and the heat dissipation component according to the temperature information of the reagent plate position and the temperature information of the heat dissipation component so that the temperature of the reagent plate position reaches the set range.

[0016] Optionally, the controlling the temperature adjustment component according to the temperature information of the reagent plate position and the temperature information of the heat dissipation component so that the temperature of the reagent plate position reaches the set range includes:

[0017] When the current temperature of the heat dissipation component is greater than the first set value, setting the current temperature of the reagent plate position as the current target temperature;

[0018] If the current temperature of the heat dissipation component drops below the second set value, setting the initial target temperature as the current target temperature.

[0019] Optionally, controlling the temperature regulating component according to the reagent plate position temperature information and the heat dissipation component temperature information to make the temperature of the reagent plate position reach the set range includes:

[0020] When the current heat dissipation component temperature is greater than the third set value and the current heat dissipation component temperature is higher than the current reagent plate position temperature by the fourth set value, the current reagent plate position temperature is set as the current target temperature;

[0021] If the current heat dissipation component temperature drops to the fifth set value, the initial target temperature is set as the current target temperature.

[0022] Optionally, the first set value is greater than the second set value; the third set value is greater than the fifth set value.

[0023] In another aspect, the present application provides a gene sequencing pretreatment system, including the refrigeration control module described in any one of the above.

[0024] To make the features and advantages of the present application more obvious and understandable, some embodiments are specifically given below and described in detail in conjunction with the accompanying drawings as follows. Description of the Drawings

[0025] To more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the following will briefly introduce the drawings required for use in the description of the embodiments or the prior art. Obviously, the drawings in the following description are only some embodiments of the present application. For those of ordinary skill in the art, other drawings can be obtained based on these drawings without creative efforts.

[0026] Figure 1 is a schematic diagram of the nucleic acid extraction process provided by the embodiment of the present application;

[0027] Figure 2 is a schematic diagram of the structure of the gene sequencing pretreatment system in the embodiment of the present application;

[0028] Figure 3 is a schematic diagram of the structure of the quality control system in the embodiment of the present application;

[0029] Figure 4 is a schematic diagram of the structure of the library construction system in the embodiment of the present application;

[0030] Figure 5 is a schematic diagram of the structure of the electric control system in the embodiment of the present application;

[0031] Figure 6 is a schematic diagram of the structure of the refrigeration control module in the embodiment of the present application;

[0032] Figure 7 is a cross-sectional view of the refrigeration control module in the embodiment of the present application;

[0033] Figure 8 is a schematic exploded view of the refrigeration control module according to an embodiment of the present application;

[0034] Figure 9 is a schematic block diagram of the temperature control unit of the refrigeration control module according to an embodiment of the present application;

[0035] Figure 10 is a schematic structural diagram of the temperature control component in an embodiment of the present application.

[0036] In the figure: 1. Refrigeration control module of reagent container; 1-1. Temperature control unit; 1-11. Controller; 1-12. Heat dissipation fin temperature sensor; 1-13. AD sampling circuit; 1-14. Single-pole double-throw analog switch; 1-15. MOS transistor driver chip; 1-16. MOS transistor; 1-17. TEC; 1-18. Control board; 1-19. Reagent board position temperature sensor; 1-2. Communication control module; 1-3. Reagent board position; 1-4. Temperature adjustment component; 1-5. Heat dissipation component; 1-51. Heat dissipation part; 1-52. Heat insulation board; 1-53. Fan; 1-6. Temperature fuse; 1-7. Heat insulation locking component; 1-71. Locking screw; 1-72. Heat insulation pad; 1-73. Height limiting column; 1-8. Housing; 1-81. Upper housing; 1-82. Lower housing; 1-83. Side enclosure housing; 10. Nucleic acid extraction system; 20. Library construction system; 21. PCR instrument; 22. Library construction actual container; 23. Oscillation heating component; 24. Magnet assembly; 25. Working area of puncturing component; 26. Waste container; 27. Large-capacity reagent container; 30. Quality control system; 31. Quantitative analyzer; 32. Quality control operation hand component; 33. Conveyor mechanism; 34. Quality control pipetting component; 35. Construction reaction container; 36. Quality control container; 37. Detection reagent container; 40. Electric control system; 41. Central control module; 42. Nucleic acid extraction system control module; 420. Temperature control module; 421. Nucleic acid extraction platform motion control module; 422. Magnetic bar / magnetic bar sleeve motion control module; 43. Library construction system control module; 430. Library construction pipetting component motion control module; 431. Library construction operation hand component motion control module; 432. Oscillation heating component control module; 434. Refrigeration control module for reagent addition area; 44. Quality control system control module; 440. Quality control operation hand component motion control module; 441. Conveyor mechanism motion control module; 442. Quality control pipetting component motion control module; 443. Quantitative analyzer control module; 45. Auxiliary component control module; 450. Camera control module; 451. Puncturing component motion control module; 452. Ultraviolet lamp and other light source control module; 453. Air cleaning control module; 50. Host computer. Detailed implementation manners

[0037] To make the objectives, technical solutions and advantages of this application clearer, the technical solutions of this application will be described in detail below. Obviously, the described embodiments are only a part rather than all of the embodiments of this application. All other implementation manners obtained by those of ordinary skill in the art based on the embodiments in this application without creative efforts shall fall within the scope protected by this application.

[0038] It should be noted that when an element is referred to as being "fixed to" or "disposed on" another element, it can be directly on the other element or there may be a centering element present at the same time. When an element is referred to as being "connected to" another element, it can be directly connected to the other element or there may be a centering element present at the same time.

[0039] Figure 1 It is a schematic diagram of the nucleic acid extraction process. As Figure 1 shown, the nucleic acid extraction provided by the embodiments of this application is a technique for separating nucleic acids from biological samples by physical, chemical, biological methods or a combination of the above methods. It is mainly used to separate nucleic acid molecules (such as DNA or RNA) in biological samples from the biological samples for subsequent experimental analysis, such as sequencing analysis.

[0040] Taking the separation by chemical method as an example, by lysing the sample cells with a cell lysate, nucleic acid molecules can be released from the sample cells. The nucleic acid molecules and impurities such as proteins coexist in the lysate solution. If pure nucleic acid molecules are to be obtained, the lysate needs to be further purified. Taking the purification by magnetic bead method as an example, magnetic beads are added to the lysate. The nucleic acid molecules released from the sample cells are specifically adsorbed on the surface of the magnetic beads, while impurities such as proteins are not adsorbed and remain in the lysate. After reacting for a certain time, under the action of a magnetic field, the magnetic beads adsorbed with nucleic acid molecules are separated from the solution. Then, the magnetic beads adsorbed with nucleic acid molecules are washed with a washing solution to wash away impurities such as proteins. At the same time, for thorough washing, the washing can be repeated multiple times to recover the pure magnetic beads adsorbed with nucleic acid molecules. Finally, by eluting with an eluent, the adsorption between the nucleic acid molecules and the magnetic beads is released. After reacting for a certain time, under the action of the magnetic field again, the magnetic beads and the nucleic acid molecules are separated. After removing the magnetic beads, only pure nucleic acid molecules remain in the nucleic acid extraction product.

[0041] Furthermore, the embodiments of the present application provide quality control for nucleic acid extraction products. It is very important to detect (or quantitatively analyze the concentration) of nucleic acid molecules (such as DNA or RNA) in the nucleic acid extraction product solution. Generally, there are certain requirements for the total amount of nucleic acid required in the subsequent library construction process. Once the actual nucleic acid input amount exceeds the total amount of nucleic acid required in the subsequent library construction process, it will affect the amplification efficiency during library construction. Therefore, it is also necessary to detect the nucleic acid concentration in the nucleic acid extraction product before library construction. After detecting the nucleic acid concentration, the total volume of the required nucleic acid extraction product can be further determined according to the nucleic acid concentration and the total amount of nucleic acid required in the subsequent library construction process. Moreover, when the detected nucleic acid concentration is too high, it will cause the total volume of the required nucleic acid extraction product to be lower than the minimum pipetting volume of the pipetting device and affect the pipetting accuracy. Therefore, it is necessary to appropriately dilute the nucleic acid extraction product with a diluent (such as pure water) before pipetting. Several common concentration detection methods include, for example, spectrophotometry, fluorescent dye detection method, microfluidic analysis method, or capillary gel electrophoresis method.

[0042] Furthermore, the embodiments of the present application provide library construction. In next-generation sequencing (NGS) technology, the nucleic acid molecules (such as DNA or RNA) extracted from biological samples need to be fragmented by physical or enzymatic means. For example, they are fragmented by ultrasonic waves. After fragmentation, nucleic acid fragments are formed. First, the ends of the nucleic acid fragments are filled in with enzymes, and then specific enzymes are used to ligate specific DNA sequences (usually, this specific DNA sequence is also called an adapter) to both ends of the fragments. Finally, the formed nucleic acid fragments are called libraries in the industry.

[0043] To save sequencing costs, generally, multiple biological samples are simultaneously sequenced in a sequencer. To distinguish the sequencing results of different samples, when preparing libraries for different samples, a DNA sequence (usually containing 6-8 bases) that can identify the source of the sample is included in their adapters. This DNA sequence that can identify the source of the sample can also be called a sample tag (or Index, Barcode). It can be understood that each sample's library adapter contains its exclusive sample tag.

[0044] Furthermore, the embodiments of the present application provide quality control for library construction products. The quality of the constructed library is crucial for the quality of the data generated by subsequent gene sequencing. Therefore, it is necessary to detect and control the quality of the library in the library construction products before loading the samples for sequencing. Generally, the library quality detection includes at least one of library length detection, library concentration detection, and library contaminant detection. Among them, through library concentration detection (or concentration quantitative analysis), the library concentration can be detected. When the detected library concentration is too high, it will cause the total volume of the library construction products required for subsequent sequencing to be lower than the minimum pipetting volume of the pipetting device and affect the pipetting accuracy. Therefore, it is necessary to appropriately dilute the library construction products with a diluent (such as pure water) before pipetting. In addition, due to the differences in the library concentrations of multiple biological samples and the differences in the sequencing data output, the total volumes of the library construction products of multiple biological samples required for subsequent sequencing are different, which ultimately affects the balance of the sequencing data output of multiple biological samples. Therefore, it is also necessary to dilute the library construction products of some biological samples with a diluent (such as pure water) before pipetting to narrow the gap between the total volumes of the library construction products of multiple biological samples. Several common concentration detection methods include, for example, spectrophotometry, fluorescent dye detection, microfluidic analysis, or capillary gel electrophoresis.

[0045] Here, it should be noted that for the quality control of library construction products and the quality control of nucleic acid extraction products, the concentration detection can use the same method or different methods respectively. The present application does not make any limitations on this.

[0046] Figure 2 It is a schematic structural diagram of the gene sequencing pre-treatment system in the embodiments of the present application. Furthermore, the gene sequencing pre-treatment system (or sequencing pre-treatment instrument) provided by the embodiments of the present application includes: a nucleic acid extraction system 10, a library construction system 20, a quality control system 30, an electronic control system 40, and a host computer 50. Among them:

[0047] The nucleic acid extraction system 10 is configured to controllably release nucleic acid molecules (such as DNA or RNA) from biological samples;

[0048] The library construction system 20 is configured to controllably prepare nucleic acid molecules (such as DNA or RNA) into libraries that can be used for loading samples for sequencing;

[0049] The quality control system 30 is configured to controllably detect the concentration of nucleic acid molecules in the nucleic acid extraction products and adjust the concentration of nucleic acid molecules to a pre-required concentration range according to the detection results, and / or controllably detect the concentration of the library in the library construction products and adjust the concentration of the library to a pre-required concentration range according to the detection results;

[0050] The electronic control system 40 is configured to control the operation and work of the nucleic acid extraction system 10, the library construction system 20, and the quality control system 30 according to the instructions of the host computer 50;

[0051] The host computer 50 is configured to control the operation and work of the nucleic acid extraction system 10, the library construction system 20, and the quality control system 30 by sending control instructions to the electronic control system 40.

[0052] Among them, for the nucleic acid extraction system 10, taking chemical separation and magnetic bead purification as an example, the nucleic acid extraction system 10 at least includes a nucleic acid extraction platform and a magnetic rod / magnetic rod sleeve assembly. Among them, an extraction operation container (such as a single reagent strip or a deep well plate) and a heating device (such as a heating block) are arranged on the nucleic acid extraction platform. In addition to accommodating one or more reagents required for nucleic acid extraction (such as cell lysate, washing solution, elution solution), the extraction operation container can also accommodate biological samples and magnetic particles (such as magnetic beads), and provide a reaction space for various chemical reactions (such as lysis reaction, washing reaction, elution reaction) during the nucleic acid extraction process; the heating device can provide suitable reaction temperature and reaction conditions for various chemical reactions occurring in the extraction operation container. The magnetic rod sleeve is sleeved on the magnetic rod to prevent the magnetic rod from directly contacting the nucleic acid extraction reagent and corroding the magnetic rod. After the magnetic rod / magnetic rod sleeve assembly enters the extraction operation container through the motion mechanism, it can provide a necessary magnetic field environment for the washing reaction and elution reaction during the nucleic acid extraction process.

[0053] It should be noted here that the nucleic acid extraction system 10 can perform nucleic acid extraction processing on multiple biological samples in batches.

[0054] For the quality control system 30, as Figure 3 shown, the quality control system 30 at least includes a quantitative analyzer 31, a quality control operation hand assembly 32 ( Figure 3 only its working area is shown), a transfer mechanism 33, a quality control pipetting assembly 34 ( Figure 3 only its working area is shown), a construction reaction container 35, a quality control container 36, and a detection reagent container 37. It should be noted that Figure 3 this is only schematic and should not be construed as a limitation on the positions of the various parts.

[0055] Among them, the construction reaction container 35 (such as a microplate) can accommodate nucleic acid extraction products and library construction products, and further provide a reaction space for some chemical reactions during the library construction process; the quality control container 36 (such as a centrifuge tube) can accommodate the test substance and can be placed in a quantifier for detection; the test reagent container 37 (such as a reagent kit) can accommodate one or more reagents required for the concentration detection by the quantitative analyzer 31 and a diluent for adjusting the concentrations of nucleic acid extraction products and library construction products. The construction reaction container 35, the quality control container 36, and the test reagent container 37 are respectively located in their respective storage areas, the quality control operation hand assembly 32 and the quality control pipetting assembly 34 work in their respective working areas, the storage area of the quality control container 36 is within the working area of the quality control operation hand assembly 32, and the storage areas of the construction reaction container 35 and the quality control reagent container 37 are within the working area of the quality control pipetting assembly 34. A transfer mechanism 33 is provided between the working area of the quality control operation hand assembly 32 and the working area of the quality control pipetting assembly 34, and the transfer mechanism 33 can reciprocally transfer the quality control container 36 between the working area of the quality control operation hand assembly 32 and the working area of the quality control pipetting assembly 34.

[0056] Before the quality control starts, the quality control operation hand assembly 32 is responsible for taking out the quality control container 36 from the storage area of the quality control container 36 and placing it on the transfer mechanism 33. The transfer mechanism 33 transfers the quality control container 36 to the working area of the quality control pipetting assembly 34. The quality control pipetting assembly 34 is responsible for sucking a certain amount of test reagent from the test reagent container 37 and adding it to the quality control container 36. Then, the transfer mechanism 33 transfers the quality control container 36 (already added with the test reagent) back to the working area of the quality control operation hand assembly 32, and the quality control operation hand assembly 32 is responsible for putting the quality control container 36 (already added with the test reagent) back into the storage area of the quality control container 36.

[0057] In addition, if it is the quality control of nucleic acid extraction products, the quality control pipetting assembly 34 is also responsible for sucking the nucleic acid extraction products from the extraction operation container and adding them to the construction reaction container 35.

[0058] After the quality control starts, the quality control operator component 32 is responsible for taking out the quality control container 36 (already added with the detection reagent) from the storage area of the quality control container 36 and placing it on the conveying mechanism 33. The conveying mechanism 33 conveys the quality control container 36 (already added with the detection reagent) to the working area of the quality control pipetting component 34. The quality control pipetting component 34 is responsible for sucking a certain amount of nucleic acid extraction product / library construction product from the construction reaction container 35 and adding it to the quality control container 36, and stirring it evenly. Then, the conveying mechanism 33 conveys the quality control container 36 (which has been successively added with the detection reagent and the nucleic acid extraction product / library construction product) back to the working area of the quality control operator component 32. The quality control operator component 32 is then responsible for putting the quality control container 36 (which has been successively added with the detection reagent and the nucleic acid extraction product / library construction product) back into the storage area of the quality control container 36.

[0059] After the detection reagent and the nucleic acid extraction product / library construction product in the quality control container 36 react for a period of time, the quality control operator component 32 is responsible for taking out the quality control container 36 from the storage area of the quality control container 36 and putting it into the quantitative analyzer 31 for concentration detection. After the detection is completed, the quality control operator component 32 is then responsible for taking out the quality control container 36 and putting it back into the storage area.

[0060] If the detected nucleic acid molecule concentration / library concentration is higher than the required concentration, the quality control pipetting component 34 is also responsible for sucking a certain amount of pure water from the detection reagent container 37 and adding it to the construction reaction container 37 for dilution.

[0061] It should be noted here that the quality control system 30 can perform quality control processing on the nucleic acid extraction products / library construction products of multiple biological samples in batches. In the scenario of batch processing, the quality control operator component 32 can take and place the quality control containers 36 one by one in sequence, or can take and place multiple quality control containers 36 at one time; correspondingly, the conveying mechanism 33 can convey the quality control containers 36 one by one, or can convey multiple quality control containers 36 at one time; the quality control pipetting component 34 can be a single-channel pipetting component, sucking the detection reagent successively and adding it to the quality control container 36 successively, or can be a multi-channel pipetting component, sucking the detection reagent in batches at one time and adding it to multiple quality control containers 36 in batches at one time, and can be freely set according to the occupied space and work efficiency specifically. Figure 2 Just for an example, in this example, the quality control operator component 32 takes and places the quality control containers 36 one by one. There are two container positions set on the conveying mechanism 33, and each can convey one quality control container 36 in the opposite direction reciprocally. The quality control pipetting component 34 is a single-channel pipetting component.

[0062] In one implementable manner, the quality control pipetting assembly 34 can be a pipetting pump. To cooperate with the operation of the pipetting pump, a pipette tip for pipetting needs to be equipped for the pipetting pump. When the pipetting operation starts, the pipetting pump sleevs the pipette tip on its end. After the pipetting operation is completed, the pipetting pump detaches the pipette tip from its end. Correspondingly, the quality control system 30 is also provided with a pipette tip storage area, as Figure 3 shown.

[0063] For the library construction system 20, as Figure 4 shown, the library construction system 20 at least includes a PCR instrument 21, a library construction manipulator assembly ( Figure 4 only its working area is shown in the figure), a library construction pipetting assembly ( Figure 4 only its working area is shown in the figure), a library construction reagent container 22, a shaking and heating assembly 23, and a magnet assembly 24. It should be noted that Figure 4 is only schematic and should not be construed as a limitation on the positions of the respective parts.

[0064] Among them, the library construction reagent container 22 (such as a reagent kit) can accommodate one or more reagents required for library construction. The library construction reagent container 22, the shaking and heating assembly 23, and the magnet assembly 24 are respectively located in their respective storage areas, and their respective storage areas are all within the working area ranges of the library construction manipulator assembly and the library construction pipetting assembly. The storage area of the library construction reagent container 22 generally needs to be in a low-temperature refrigerated environment to facilitate the low-temperature refrigeration of the library construction reagents. The shaking and heating assembly 23 is provided with a purification container (such as a deep-well plate) and a shaking and heating device. The purification container can provide a reaction space for magnetic bead purification during library construction, and the shaking and heating device can provide suitable reaction temperatures and reaction conditions for magnetic bead purification. At the same time, the magnet assembly 24 can provide a necessary magnetic field environment for magnetic bead purification.

[0065] After the nucleic acid extraction quality control is completed, the library construction operator component is responsible for taking out the construction reaction container 35 (which has been added with nucleic acid extraction products) from the quality control system 30 and placing it in a specific storage area in the library construction system 20. In this storage area, various reaction reagents are added to the construction reaction container 35. For the convenience of description, this storage area can be called the reagent addition area. Since the nucleic acid is stored in the construction reaction container, the reagent addition area generally needs to be in a low-temperature refrigeration environment to facilitate the low-temperature refrigeration of the nucleic acid. Since the entire library construction process includes multiple reaction steps, for each reaction step, the library construction pipetting component is first responsible for sucking the corresponding reaction reagent from the library construction reagent container 22 and adding it to the construction reaction container 35 (which has been added with nucleic acid extraction products). Then, the library construction operator component is responsible for putting the construction reaction container 35 (which has been successively added with nucleic acid extraction products and the corresponding reaction reagents) into the PCR instrument 21 for reaction. After the reaction is completed, the library construction operator component takes out the construction reaction container 35 from the PCR instrument 21 and returns it to the specific area to wait for the addition of the reaction reagent for the next reaction, and repeats the above process.

[0066] Among them, during the library construction process, after adaptors are ligated to both ends of nucleic acid fragments, the ligation products need to be purified, and a pure library can be obtained after purification. Additionally, since the amount of the library obtained at this time is small, library amplification is usually required, and the amplification products also need to be purified to obtain a pure library after amplification. If the magnetic bead method is used for purification, in addition to accommodating one or more reagents required for library construction (including the washing solution and elution solution required for magnetic bead purification) in the library construction reagent container 22, magnetic beads or other magnetic particles can also be accommodated. During the magnetic bead purification reaction of the ligation products or amplification products, the library construction pipetting assembly is responsible for first aspirating the ligation products / amplification products from the construction reaction container 35 and adding them to the purification container of the oscillation heating assembly 23, and then aspirating magnetic beads from the library construction reagent container 22 and adding them to this purification container (which has already been added with ligation products / amplification products). After reacting for a certain period of time, the library construction manipulator assembly is responsible for transferring this purification container (with the library adsorbed on the surface of the magnetic beads) to the magnet assembly 24. Under the action of the magnetic field, the magnetic beads adsorbed with the library are separated from the solution. The library construction pipetting assembly then aspirates the supernatant in this purification container, leaving the magnetic beads adsorbed with the library. The library construction pipetting assembly continues to aspirate the washing solution from the library construction reagent container 22 and add it to this purification container. After reacting for a certain period of time, the supernatant is aspirated away again. According to the experimental requirements, the library construction pipetting assembly can operate repeatedly for multiple washes. After the washing is completed, the library construction manipulator assembly transfers this purification container to the oscillation heating assembly 23. The library construction pipetting assembly continues to aspirate the elution solution from the library construction reagent container 22 and add it to this purification container. After reacting for a certain period of time, the adsorption between the library and the magnetic beads is released. The library construction pipetting assembly then aspirates the supernatant in this purification container (i.e., the library construction product) and adds it to the construction reaction container 35.

[0067] Generally, a sealing film is attached to the upper surface of the library construction reagent container 22 to facilitate the storage and transportation of the internal reagents. After the reagent container is loaded into the interior of the sequencing pretreatment instrument, the sealing film needs to be punctured through the puncturing assembly ( Figure 4 only its working area is shown) so that the corresponding pipetting assembly can aspirate the reagents from the library file reagent container 22, and the storage area of the library construction reagent container 22 is within the working area 25 of the puncturing assembly.

[0068] In addition, considering that the required amounts of magnetic beads, washing solution, and elution solution in the magnetic bead purification process are large and do not need to be stored in a low-temperature refrigerated environment, in addition to the library construction reagent container 22, the library construction system 20 can further be provided with a large-capacity reagent container 27 for storing large-capacity reagents such as magnetic beads, washing solution, and elution solution.

[0069] It should be noted here that the library construction manipulator component and the library construction pipetting component can be set independently. Considering that the library construction manipulator component and the library construction pipetting component do not need to work in parallel, they can also be integrated into one body to save space. In addition, the library construction system 20 can batch process the nucleic acid extraction products of multiple biological samples for library construction.

[0070] In an implementable manner, the library pipetting component can be a pipetting pump. To cooperate with the work of the pipetting pump, pipette tips for pipetting also need to be equipped for the pipetting pump. When the pipetting work starts, the pipetting pump sleevs a pipette tip on its end. After the pipetting work is completed, the pipetting pump detaches the pipette tip from its end. Correspondingly, the library construction system 20 is also provided with a pipette tip storage area, and the used pipette tips will be put into the waste container 26, as Figure 4 shown.

[0071] For the electric control system 40, as Figure 5 shown, according to the functional division, the electric control system 40 mainly includes a central control module (or central control board) 41, control modules that implement various control functions, and various sensors, which can collect information reflecting various operating states of the instrument.

[0072] Among them, the central control module 41, as the center connecting the host computer 50 and each control module, receives the control instructions sent by the host computer 50 through a communication interface (for example, RS232 interface), and after parsing, verifying, and re-encoding, issues the instructions to the corresponding control module to achieve unified and orderly control of each control module. Each control module cooperates methodically under the control to achieve the purpose of constructing a sequencing library before gene sequencing.

[0073] As Figure 5As shown, the electronic control system 40 may include, for example, but is not limited to: a nucleic acid extraction system control module 42, a library construction system control module 43, a quality control system control module 44, and an auxiliary component control module 45. Among them, taking the purification by magnetic bead method as an example, the nucleic acid extraction system control module 42 at least includes: a temperature control module 420, a nucleic acid extraction platform movement control module 421, and a magnetic rod / magnetic rod sleeve movement control module 422; the quality control system control module 44 at least includes: a quality control manipulator assembly movement control module 440, a transfer mechanism movement control module 441, a quality control pipetting assembly movement control module 442, and a quantitative analyzer control module 443; the library construction system control module 43 at least includes: a library construction pipetting assembly movement control module 430, a library construction manipulator assembly movement control module 431, an oscillation heating assembly control module 432, and a refrigeration control module 1; the auxiliary component control module 45 at least includes: a camera control module 450, a puncture component movement control module 451, an ultraviolet lamp and other light source control module 452, and an air cleaning control module 453. Each module will be described in detail below.

[0074] The temperature control module 420 can provide suitable reaction temperatures and reaction conditions for various chemical reactions (such as cell lysis reaction, washing reaction, elution reaction) occurring on the nucleic acid extraction platform by controlling heating devices. For example, the heating device here can be a heating sheet, or it can also be a TEC (thermoelectric cooler) module. And, in order to better achieve temperature control, the temperature control module 420 can also achieve closed-loop control according to the temperature collected by the temperature sensor.

[0075] The nucleic acid extraction platform movement control module 421 and the magnetic rod / magnetic rod sleeve movement control module 422 can cooperate with each other to achieve the relative movement between the nucleic acid extraction platform and the magnetic rod / magnetic rod sleeve, and complete each operation step of nucleic acid extraction. Taking the movement of the nucleic acid extraction platform in a two-dimensional plane as an example, the nucleic acid extraction platform movement control module 421 can drive the X-direction motor and the Y-direction motor to move respectively by controlling the driver, and then drive the nucleic acid extraction platform to move in the X direction and the Y direction (the X direction and the Y direction are perpendicular to each other on the horizontal plane). The magnetic rod / magnetic rod sleeve movement control module 422 can drive the Z-direction motor to drive the magnetic rod and the magnetic rod sleeve to move in the Z direction respectively by controlling the driver (the Z direction is perpendicular to the horizontal plane formed by the X and Y directions).

[0076] The quality control manipulator assembly movement control module 440 can drive the X-direction motor, the Y-direction motor, and the Z-direction motor to move respectively by controlling the driver, and then drive the quality control manipulator assembly to move in the X direction, the Y direction, and the Z direction.

[0077] The transfer mechanism movement control module 441 can drive the X-direction motor to drive the transfer mechanism to move in the X direction by controlling the driver.

[0078] The quality control pipetting component motion control module 442 can drive the X-axis motor, Y-axis motor, and Z-axis motor to move respectively by controlling the driver, thereby driving the quality control pipetting component to move in the X-axis, Y-axis, and Z-axis directions.

[0079] The quantitative analyzer control module 443 can control the quantitative analyzer to detect the concentration of at least one of the nucleic acid extraction product and the library construction product, and output the detection result.

[0080] The library construction pipetting component motion control module 430 can drive the X-axis motor, Y-axis motor, and Z-axis motor to move respectively by controlling the driver, thereby driving the library construction pipetting component to move in the X-axis, Y-axis, and Z-axis directions.

[0081] The library construction manipulator component motion control module 431 can drive the X-axis motor, Y-axis motor, and Z-axis motor to move respectively by controlling the driver, thereby driving the library construction manipulator component to move in the X-axis, Y-axis, and Z-axis directions.

[0082] The oscillation heating component control module 432 can provide suitable reaction temperatures and reaction conditions for various reactions in the magnetic bead purification (such as washing reaction, elution reaction) by controlling the oscillation device and heating device. For example, the heating device here can be a heating sheet, or it can also be a TEC (thermoelectric cooler) module. And, in order to better achieve temperature control, the oscillation heating component control module 432 can also achieve closed-loop control according to the temperature collected by the temperature sensor.

[0083] The reagent container refrigeration control module 1 can provide a suitable refrigeration temperature for the library construction reagent container 22 by controlling the heating device and refrigeration device. For example, the heating device here can be a TEC (thermoelectric cooler) module, a heating sheet, etc., and the refrigeration device can be a TEC (thermoelectric cooler) module, etc., and at the same time, a heat dissipation device such as a fan is configured for heat dissipation. And, in order to better achieve temperature control, the refrigeration control module 1 can also achieve closed-loop control according to the temperature collected by the temperature sensor.

[0084] The reagent addition area refrigeration control module 434 can provide a suitable refrigeration temperature for the reagent addition area by controlling the heating device and refrigeration device. For example, the heating device here can be a TEC (thermoelectric cooler) module, a heating sheet, etc., and the refrigeration device can be a TEC (thermoelectric cooler) module, etc., and at the same time, a heat dissipation device such as a fan is configured for heat dissipation. And, in order to better achieve temperature control, the reagent addition area refrigeration control module 434 can also achieve closed-loop control according to the temperature collected by the temperature sensor.

[0085] The camera control module 440 can drive the X-axis motor, Y-axis motor, and Z-axis motor to move respectively by controlling the driver, thereby driving the camera to move in the X direction, Y direction, and Z direction, and controlling the camera to take pictures of the consumables (such as extraction operation containers, library construction reagent containers) in the sequencing pre-treatment instrument after reaching the target position and report them to the host computer. For example, a two-dimensional code is set on the consumable, and the two-dimensional code carries consumable information. By controlling the camera to take pictures of the two-dimensional code on the consumable, the host computer can identify the consumable information according to the two-dimensional code. In addition, the camera control module can also control the camera to take pictures of relevant containers (such as the library construction reagent container 22, the construction reaction container 35, the purification container placed on the oscillation heating component 25, the tip container for accommodating the pipette pump pipetting placed in the tip storage area, etc.) and report them to the host computer 50, so that the host computer 50 can check the placement position, placement direction of the relevant containers and the relevant consumable information before the pre-treatment experiment starts to determine whether each container is placed correctly and whether the consumables are used correctly.

[0086] The puncturing component motion control module 441 can drive the X-axis motor, Y-axis motor, and Z-axis motor to move respectively by controlling the driver, thereby driving the puncturing component to move in the X direction, Y direction, and Z direction.

[0087] The ultraviolet lamp and other light source control module 442 includes: an ultraviolet lamp control sub-module, a status indicator light control sub-module, and a decorative lamp control sub-module ( Figure 4 not shown in the figure). Among them, the ultraviolet lamp control sub-module can control the ultraviolet lamp to work in a stable light power state so that the ultraviolet rays emitted by the ultraviolet lamp can disinfect the sequencing pre-treatment instrument; the status indicator light control sub-module can control the indicator light to work in a stable light power state and indicate the working state of the sequencing pre-treatment instrument by controlling the color of the indicator light; the decorative lamp control sub-module can control the light strip to work in a stable light power state to increase the aesthetics of the sequencing pre-treatment instrument.

[0088] The air cleaning control module 443 provides clean air for the inside of the instrument chassis and the inside of the nucleic acid extraction system by controlling the air intake mechanism (such as a blower) and the air exhaust mechanism (such as a fan).

[0089] In addition to the above various control modules, the electronic control system 40 also needs to collect information reflecting the operating state of the instrument in real time through various sensors and report it to the host computer 50 through the central control module 41 for the host computer 50 to detect the working state of the instrument and ensure the stable operation of the instrument.

[0090] Various sensors may include, for example, but are not limited to: temperature sensors for collecting the temperatures of key components inside the sequencer, sensors for detecting the in-place status of relevant components (including but not limited to limit position detection and zero position detection), etc.

[0091] Among them, the in-place status detection may include, for example, but is not limited to: the in-place status detection of the nucleic acid extraction platform, the magnetic bar / magnetic bar sleeve assembly, the quality control manipulator assembly, the conveying mechanism, the quality control pipetting assembly, the library construction manipulator assembly, the library construction pipetting assembly, the nucleic acid extraction system chamber door, and the instrument chamber door.

[0092] For example, the temperature sensor can collect the temperatures of the nucleic acid extraction platform, the oscillating heating component, the reagent addition area, etc. The central control module can further form a closed-loop control based on the temperatures collected by the temperature sensor.

[0093] In addition, for another example, the temperature sensor can collect the temperature of the heat sink in the TEC module. The central control module can further determine whether the TEC module is operating normally based on the temperature of the heat sink, and perform controls such as alarm and stop operation in case of abnormal operation.

[0094] After the central control module 41 reports the information collected by the sensor to the host computer 50, the host computer 50 detects the working status of the instrument, and issues an instruction indicating the working status according to the detection result. The central control module 41 forwards the instruction to the status indicator light control sub-module, and the status indicator light control sub-module controls the indicator light to indicate the working status of the instrument according to the instruction. For example, the RGB three-color indicator light is used to indicate the working status of the instrument (for example, including the running status, the fault status, etc.).

[0095] The central control module 41 can also receive the input power supply, convert the input power supply into the working power supplies required by each control module according to the requirements, and output them.

[0096] Among them, the reagent container refrigeration control module 1 provides a low-temperature refrigeration environment for the storage of the library construction reagent container 22, which is convenient for the low-temperature refrigeration of the library construction reagent. To realize the fully automated process of the instrument and ensure the storage temperature of the reagent plate position where the reagent container is located, the refrigeration control module 1 is integrated under the reagent plate position, which is convenient for the storage of the reagent container. In this case, due to space limitation and noise reduction, the heat dissipation fin size is small and the fan air volume is small. To ensure that the Peltier can maintain the optimal energy efficiency in any case and enable the reagent plate position to reach the specified temperature, the present application provides the following refrigeration control module 1 (i.e., the reagent container refrigeration control module 1) and its temperature control system.

[0097] Such as Figure 8 、 Figure 9As shown in the figure, on the one hand, the present application provides that the refrigeration control module 1 includes: a temperature control unit 1-1, a reagent plate position 1-3, a temperature adjustment component 1-4, and a heat dissipation component 1-5 arranged in sequence from top to bottom. The temperature control unit 1-1 includes a temperature control component and a temperature sensor connected to the temperature control component. Two temperature sensors are provided, which are respectively connected to the reagent plate position 1-3 and the heat dissipation component 1-5. The temperature control component adjusts the temperature adjustment component 1-4 or the temperature adjustment component 1-4 and the heat dissipation component 1-5 according to the reagent plate position temperature information and the heat dissipation component temperature information fed back by the temperature sensor, so that the temperature of the reagent plate position 1-3 reaches the set range.

[0098] Specifically, due to the overall size and space limitation of the refrigeration control module 1, the heat dissipation component 1-5, for example, can be set as a fan for air volume control and noise reduction treatment, resulting in the heat dissipation effect of the heat dissipation component 1-5 not being in the optimal state. However, in the prior art, the heat dissipation situation of the heat dissipation component 1-5 is often not concerned, and only whether the temperature of the target area, that is, the reagent plate position 1-3, reaches the target value is monitored. If the temperature of the reagent plate position 1-3 does not reach the target value, the temperature adjustment component 1-4 is controlled to continue working. However, if the heat dissipation effect of the heat dissipation component 1-5 is not in the optimal state or its temperature is relatively high, the heat dissipation efficiency is very low. At this time, if the temperature adjustment component 1-4 continues to work, the temperature adjustment component 1-4 itself generates more heat due to high-power operation and it is difficult to dissipate heat through the heat dissipation component 1-5, thereby making it difficult for the temperature of the reagent plate position 1-3 to quickly reach the target value.

[0099] Among them, the temperature adjustment component 1-4 can be a thermoelectric cooler, that is, a Peltier or a TEC.

[0100] In order to quickly bring the temperatures of reagent plate positions 1 - 3 to the target value, for example, within the range of 4 - 8 °C, the temperature control unit 1 - 1 of the refrigeration control module 1 obtains the temperature information of reagent plate positions 1 - 3 and the heat dissipation component 1 - 5 in real time through two temperature sensors, namely the reagent plate position temperature sensor 1 - 19 and the heat dissipation fin temperature sensor 1 - 12. According to the temperature information of reagent plate positions 1 - 3, it controls the working state of the temperature adjustment component 1 - 4 when cooling reagent plate positions 1 - 3, and at the same time adjusts the working state of the temperature adjustment component 1 - 4 and / or regulates the working power of the heat dissipation component 1 - 5 according to the temperature information of the heat dissipation component 1 - 5, so as to quickly reduce the temperature of the heat dissipation component 1 - 5, thereby improving its heat dissipation effect on the temperature adjustment component 1 - 4, enabling the heat generated when the temperature adjustment component 1 - 4 works to be quickly taken away, and improving its cooling efficiency for reagent plate positions 1 - 3; among them, adjusting the working state of the temperature adjustment component 1 - 4 includes temporarily reducing the power of the temperature adjustment component 1 - 4 or stopping the operation of the temperature adjustment component 1 - 4. At this time, the heat generated by the temperature adjustment component 1 - 4 will be greatly reduced, which is conducive to first dissipating the heat of the heat dissipation component 1 - 5 and reducing the temperature of the heat dissipation component 1 - 5, and then readjusting the working state of the temperature adjustment component 1 - 4 to cool reagent plate positions 1 - 3 again at a higher power and reach the target value.

[0101] In an embodiment, when the current temperature of the heat dissipation component 1 - 5 is greater than the first set value, the current temperature of the reagent plate position 1 - 3 is set as the current target temperature; if the current temperature of the heat dissipation component drops below the second set value, the initial target temperature is set as the current target temperature. Further, the second set value is less than or equal to the first set value. When the current temperature of the heat dissipation component 1 - 5 is greater than the first set value, the current temperature of the reagent plate position 1 - 3 is set as the current target temperature. At this time, the temperature adjustment component 1 - 4 is adjusted to a low - power working state, and the heat generated by it is reduced, which is convenient for the temperature of the heat dissipation component 1 - 5 to quickly decrease. When the current temperature of the heat dissipation component drops below the second set value, the initial target temperature is set as the current target temperature. In this way, after the temperature of the heat dissipation component 1 - 5 drops to the second set value, the initial target temperature is set as the current target temperature again. At this time, because the temperature of the heat dissipation component 1 - 5 is relatively low, the heat generated when the temperature adjustment component 1 - 4 cools the reagent plate position 1 - 3 can be taken away by the heat dissipation component 1 - 5, so that the temperature of the reagent plate position 1 - 3 can quickly drop to the target temperature.

[0102] Specifically, the optimized algorithm is programmed as follows: if the temperature of the heat dissipation components 1-5 is greater than the first set value, such as 55°C, the initial target temperature Sv is stored in the variable Sv2, and the temperature values Pv of the current reagent plate positions 1-3 are assigned to the target temperature value Sv. In this way, the temperature control target temperature will be maintained around Sv. At this time, if the power of the heat dissipation components 1-5 decreases, the temperature of the heat dissipation components will gradually decrease. If it drops below the second set value, such as below 30°C, then the value of the variable Sv2 is assigned to the target temperature value Sv, and the temperature will drop to around Sv (the initially set initial target temperature value).

[0103] In one embodiment, when the current temperature of the heat dissipation component is greater than the third set value and the current temperature of the heat dissipation component is higher than the temperature of the current reagent plate positions 1-3 by the fourth set value, the temperature of the current reagent plate positions 1-3 is set as the current target temperature; when the temperature of the current heat dissipation components 1-5 drops to the fifth set value, the initial target temperature is set as the current target temperature. Further, the fifth set value is less than or equal to the third set value. When the temperature of the current heat dissipation components 1-5 is greater than the third set value and the current temperature of the heat dissipation component is higher than the temperature of the current reagent plate positions 1-3 by the fourth set value, the temperature of the current reagent plate positions 1-3 is set as the current target temperature. At this time, the temperature control component 1-4 operates in a low-power state, and the heat generated by it decreases, which is convenient for the temperature of the heat dissipation components 1-5 to quickly decrease. When the temperature of the current heat dissipation component drops below the fifth set value, the initial target temperature is set as the current target temperature. In this way, after the temperature of the heat dissipation components 1-5 drops to the fifth set value, the initial target temperature is reset as the current target temperature again. At this time, since the temperature of the heat dissipation components 1-5 is relatively low, the heat generated when the temperature control component 1-4 cools the reagent plate positions 1-3 can be taken away by the heat dissipation components 1-5, so that the temperature of the reagent plate positions 1-3 can quickly drop to the target temperature. In this embodiment, the third set value and the first set value in the previous embodiment can be set to be the same or different, and the fifth set value and the second set value can be set to be the same or different.

[0104] Specifically, the optimized algorithm is programmed as follows: if the difference between the temperature of the heat dissipation components 1-5 and the temperature of the current reagent plate positions 1-3 is greater than the fourth set value, such as 50°C, and the temperature of the heat dissipation components 1-5 is greater than the third set value, such as 55°C, the initial target temperature Sv is stored in the variable Sv2, and the temperature values Pv of the current reagent plate positions 1-3 are assigned to the target temperature value Sv. In this way, the temperature control target temperature will be maintained around Sv. At this time, if the power of the heat dissipation components 1-5 decreases, the temperature of the heat dissipation components will gradually decrease. If it drops below the fifth set value, such as below 30°C, then the value of the variable Sv2 is assigned to the target temperature value Sv, and the temperature will drop to around Sv (the initially set initial target temperature value).

[0105] As an optional implementation manner, the temperature control component is respectively connected to the temperature sensor through the ADC sampling circuit 1-13.

[0106] Specifically, the temperature control unit 1-1 mainly obtains the AD value of the temperature sensor in the form of a resistance bridge through an ADC sampling chip, and converts it into temperature to provide it to the temperature control component; among them, the reagent plate position temperature sensor 1-19 is located in the mounting hole of the reagent plate position 1-3, and a heat-conducting medium is used to ensure full contact between the two; the heat dissipation fin temperature sensor 1-12 is located in the mounting hole of the heat dissipation fin, and a heat-conducting medium is used to ensure full contact between the two.

[0107] As an optional implementation manner, the temperature adjustment component 1-4 is set as a Peltier, and the heat dissipation component 1-5 includes a heat dissipation fin 1-51, and the Peltier is arranged on the heat dissipation fin 1-51. Further, the heat dissipation component further includes a fan 1-53, the fan 1-53 is arranged below the heat dissipation fin 1-51, and the temperature information of the heat dissipation component is the temperature information of the heat dissipation fin. Further, a heat insulation plate 1-52 is arranged between the heat dissipation fin 1-51 and the reagent plate position 1-3, a through groove is arranged in the middle of the heat insulation plate 1-52, and the Peltier is located in the through groove.

[0108] Specifically, as Figure 7 、 Figure 8 shown, the Peltier is located in the through groove of the heat insulation plate 1-52, and its upper and lower surfaces are coated with a heat-conducting medium, one side of which is connected to the reagent plate position 1-3 of the target temperature control plate, and the other side is connected to the heat dissipation fin 1-51; the heat insulation plate 1-52 is located between the reagent plate position 1-3 and the heat dissipation fin 1-51 for filling the gap; the reagent plate position 1-3, the heat insulation plate 1-52, and the heat dissipation fin 1-51 are installed and locked through a heat insulation locking component 1-7. The heat insulation locking component 1-7 includes a locking screw 1-71, a heat insulation pad 1-72, and a height limiting column 1-73. The height limiting column 1-73 is located between the reagent plate position 1-3 and the heat dissipation fin 1-51 and is in the through hole of the heat insulation plate 1-72, providing an accurate installation height and space for the Peltier. The locking screw 1-71 passes through the heat insulation pad 1-72 and is connected to the heat dissipation fin 1-51 to lock the reagent plate position 1-3, the Peltier, and the heat dissipation fin 1-51; as the main temperature control execution component of the refrigeration control module 1, the Peltier is arranged on the heat dissipation fin 1-51 and is located below the reagent plate position 1-3, facilitating direct temperature control of the reagent plate position 1-3. The fan 1-53 is arranged below the heat dissipation fin 1-51. The temperature control unit controls the Peltier and the fan 1-53 according to the heat dissipation fin temperature information and the reagent plate position temperature information. The temperature control unit adjusts the working power of the fan 1-53 to adjust its heat dissipation effect on the heat dissipation fin 1-51. For example, when the temperature of the heat dissipation fin 1-51 is too high, the power of the fan 1-53 can be increased so that it can dissipate heat from the heat dissipation fin 1-51 faster, enabling the heat generated when the temperature adjustment component 1-4 cools the reagent plate position 1-3 to be quickly taken away by the heat dissipation component 1-5, so that the Peltier is in the most effective working state.

[0109] As an alternative embodiment, the temperature control component is disposed on the control board 1-18, and the control board 1-18 is disposed below the heat dissipation component 1-5.

[0110] Specifically, as Figure 6 、 Figure 8 shown, the housing 1-8 of the refrigeration control module 1 includes an upper housing 1-81, a sidewall housing 1-83, and a lower housing 1-82 that are sequentially connected. The above-mentioned temperature control unit 1-1, reagent plate position 1-3, temperature adjustment component 1-4, heat dissipation component 1-5, etc. are all disposed within the housing 1-8. The fan 1-53 of the heat dissipation component 1-5 is located within the mounting hole of the lower housing 1-82 and is mounted directly below the heat dissipation fins 1-51 for dissipating heat from the heat dissipation fins 1-51. A temperature fuse 1-6 is provided in the circuit of the temperature control component. The temperature fuse 1-6 is mounted on one side of the heat dissipation fins 1-51, and a heat-conducting medium is used to ensure full contact between the two. The control board 1-18 is mounted above the lower housing 1-84 and below the fan 1-53. The sidewall housing 1-83 is located around the reagent plate position 1-3 and the heat dissipation fins 1-51 and is connected to the heat dissipation fins 1-51. Among them, a fan 1-53 switch and a fault detection unit are provided between the control board 1-18 and the fan 1-53 to facilitate the function detection and control of the fan 1-53.

[0111] As an alternative embodiment, as Figure 10 shown, the temperature control component includes a controller 1-11, a single-pole double-throw analog switch 1-14, a MOS transistor driver chip 1-15, a MOS transistor 1-16, and a thermoelectric cooler TEC1-17 that are sequentially connected. The controller 1-11 leads out two signal pins, both of which are respectively connected to two single-pole double-throw analog switches 1-14. The two single-pole double-throw analog switches 1-14 are respectively connected to a MOS transistor driver chip 1-15. Each MOS transistor driver chip 1-15 is connected to a group of MOS transistors 1-16. The output ends of the two groups of MOS transistors 1-16 are respectively connected to the TEC1-17. The two signal pins of the controller 1-11 include a PWM signal pin and a high-low level pin. The PWM signal pin is connected to different pins of the two single-pole double-throw analog switches 1-14.

[0112] Specifically, the controller 1-11 of the temperature control unit 1-1 can be set as a single-chip microcomputer. Two signals are led out from two signal pins of the single-chip microcomputer. A PWM signal and a high-low level signal are respectively connected to two single-pole double-throw analog switches 1-14. Due to different signal pins of the PWM input and different high-low levels, the PWM signal states output by the single-pole double-throw analog switches 1-14 are different. Through the control of the single-chip microcomputer, one of the signals output by the two single-pole double-throw analog switches 1-14 is the PWM signal output by the single-chip microcomputer, and the other is a low level. The signals output by the two single-pole double-throw analog switches 1-14 are respectively connected to the IN pins of two MOS tube driver chips 1-15. The H-bridge MOS tubes 1-16 are driven through the states of these pins. Two paths output by the MOS tubes 1-16 are respectively connected to both ends of the TEC 1-17. One end outputs a PWM signal and the other end is grounded. The high-low level signal output by the single-chip microcomputer is used to control which end of the output PWM signal and GND are connected to the TEC 1-17, thereby driving the Peltier temperature rise and fall of the TEC 1-17. In the prior art, generally, the single-chip microcomputer of the control circuit needs to be connected to two PWM control signals and two high-level signals to drive the TEC 1-17 to work. The control method of this application reduces the control pins of the single-chip microcomputer by half, improves the utilization rate of the single-chip microcomputer, and at the same time, the program control becomes simple, which can avoid control errors and reduce control risks.

[0113] As an optional implementation manner, it further includes a communication control module 1-2. The communication control module 1-2 is connected to the central control module 41 and is connected to the temperature control module.

[0114] Specifically, the temperature control module 420 and the communication control module 1-2 are connected to the central control module 41, dock with the central control module 41, and send commands to the refrigeration control module 1 by executing the recipe task, so that it executes the corresponding control commands.

[0115] During the operation of the refrigeration control module 1, condensate will be generated. Regarding the problem of condensate in the refrigeration control module 1, since the instrument still has a certain working time after the reagent performs an operation, at this time, the refrigeration control module 1 does not need to provide low temperature to the reagent board position 1-3 for reagent storage. Then, at this time, the temperature of the refrigeration control module 1 can be raised above 100°C, and the condensate on the refrigeration control module 1 can be evaporated dry by using the time for other experiments later.

[0116] In the description of the present application, it should be noted that the orientation or positional relationship indicated by terms such as "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", etc. is based on the orientation or positional relationship shown in the drawings. It is only for the convenience of describing the present application and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be construed as a limitation to the present application. In addition, the terms "first", "second", "third" are only used for descriptive purposes and cannot be construed as indicating or implying relative importance.

[0117] In the description of the present application, it should be noted that unless otherwise clearly specified and defined, the terms "installed", "connected", "coupled" shall be construed in a broad sense. For example, it may be a fixed connection, a detachable connection, or an integral connection; it may be a mechanical connection or an electrical connection; it may be directly connected or indirectly connected through an intermediate medium, and it may be the communication inside two elements. For those of ordinary skill in the art, the specific meanings of the above terms in the present application can be understood according to specific circumstances.

[0118] The above are only the specific embodiments of the present application, but the protection scope of the present application is not limited thereto. Any person skilled in the art within the technical scope disclosed by the present application can easily think of changes or substitutions, which should all be covered within the protection scope of the present application. Therefore, the protection scope of the present application shall be subject to the protection scope of the claims.

Claims

1. A refrigeration control module, characterized in that: include: A temperature control unit and a reagent plate position, a temperature adjustment component and a heat dissipation component are arranged in sequence from top to bottom. The temperature control unit includes a temperature control component and a temperature sensor connected to the temperature control component. Two temperature sensors are arranged, which are respectively connected to the reagent plate position and the heat dissipation component. The temperature control component adjusts the temperature adjustment component or the temperature adjustment component and the heat dissipation component according to the reagent plate position temperature information and the heat dissipation component temperature information fed back by the temperature sensor so that the temperature of the reagent plate position reaches a set range.

2. The refrigeration control module according to claim 1, characterized in that: The temperature control components are connected to the temperature sensors via ADC sampling circuits respectively.

3. The refrigeration control module according to claim 1, characterized in that: The temperature regulating component is configured as a Peltier, the heat dissipating component comprises heat dissipating fins, and the Peltier is configured on the heat dissipating fins.

4. The refrigeration control module according to claim 3, characterized in that: The heat dissipation component further includes a fan, and the fan is arranged below the heat dissipation fins. The temperature information of the heat dissipation component is the temperature information of the heat dissipation fins.

5. The refrigeration control module according to claim 4, characterized in that: A heat insulation board is arranged between the heat dissipation fin and the reagent plate position, a through groove is arranged in the middle of the heat insulation board, and the Peltier is located in the through groove.

6. The refrigeration control module according to claim 1, characterized in that: The temperature control component is arranged on a control board, and the control board is arranged below the heat dissipation component.

7. The refrigeration control module according to any one of claims 1 to 6, characterized in that: The temperature control component includes a controller, a single-pole double-throw analog switch, a MOS tube driver chip, a MOS tube and a semiconductor refrigerator TEC which are connected in sequence; the controller leads out two signal pins, which are respectively connected to the two single-pole double-throw analog switches, the two single-pole double-throw analog switches are respectively connected to one MOS tube driver chip, each of the MOS tube driver chips is connected to a group of the MOS tubes, and the output ends of the two groups of the MOS tubes are respectively connected to the TEC.

8. The refrigeration control module according to claim 7, characterized in that: The two signal pins of the controller include a PWM signal pin and a high-low level pin, and the PWM signal pin is connected to different pins of the two single-pole double-throw analog switches.

9. The refrigeration control module according to claim 8, characterized in that: It also includes a communication control module, which is connected to the central control module and the temperature control unit respectively.

10. A refrigeration control method, characterized in that: A refrigeration control module as claimed in any one of claims 1 to 9, comprising: Acquire the temperature information of the reagent plate and the temperature information of the heat dissipation component through the temperature sensor; The temperature regulating component or the temperature regulating component and the heat dissipating component are controlled according to the temperature information of the reagent plate position and the temperature information of the heat dissipating component so that the temperature of the reagent plate position reaches a set range.

11. The refrigeration control method according to claim 10, characterized in that: The step of controlling the temperature regulating component according to the temperature information of the reagent plate position and the temperature information of the heat dissipation component so that the temperature of the reagent plate position reaches a set range includes: When the current heat dissipation component temperature is greater than the first set value, the current reagent plate position temperature is set as the current target temperature; If the current temperature of the heat dissipation component drops below the second set value, the initial target temperature is set as the current target temperature.

12. The refrigeration control method according to claim 10, characterized in that: The step of controlling the temperature regulating component according to the temperature information of the reagent plate position and the temperature information of the heat dissipation component so that the temperature of the reagent plate position reaches a set range includes: When the current heat dissipation component temperature is greater than the third set value, and the current heat dissipation component temperature is higher than the current reagent plate position temperature by a fourth set value, the current reagent plate position temperature is set as the current target temperature; If the current temperature of the heat dissipation component drops to the fifth set value, the initial target temperature is set as the current target temperature.

13. The refrigeration control method according to claim 11 or 12, characterized in that: The first setting value is greater than the second setting value; the third setting value is greater than the fifth setting value.

14. A gene sequencing pre-processing system, characterized in that: It comprises a refrigeration control module as described in any one of claims 1-9.

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