A reaction control system for automated NGS library construction

Abstract

This invention belongs to the field of molecular diagnostics technology, and particularly relates to a reaction control system for automated NGS library construction. The system includes a base plate, a motion module, a top plate, a nucleic acid extraction module, a nucleic acid fragmentation module, a first driving component, a library amplification module, and a processor. The motion module is mounted on the base plate, and the top plate is directly or indirectly connected to the motion end of the motion module. Multiple first driving components are disposed on the top plate. The motion module and the first driving components can move the nucleic acid extraction module and the nucleic acid fragmentation module relative to the base plate in different directions to drive them to engage with corresponding reaction wells. The library amplification module is disposed on the base plate and provides the required temperature for the amplification reaction to the corresponding reaction wells. This invention, in conjunction with a reaction apparatus, can automate NGS library construction. The modular design facilitates adjustment, and the library amplification module's heat dissipation accelerates cooling and shortens reaction time.

Description

Technical Field

[0001] This invention belongs to the field of molecular diagnostic technology, and in particular relates to a reaction control system for automated NGS library construction. Background Technology

[0002] High-throughput sequencing, also known as next-generation sequencing (NGS), has a complex process involving multiple stages such as nucleic acid extraction, library construction, sequencing, and data analysis. Among these, library construction is one of the most critical factors determining whether the entire high-throughput sequencing process can achieve automated detection.

[0003] Library construction involves a series of operations, including nucleic acid extraction, nucleic acid fragmentation, end repair, adapter ligation, and library amplification. Currently, most library construction methods on the market are semi-automated, still requiring significant manual operation and consuming considerable manpower and time, failing to fundamentally solve the automation problem. Improper operation by laboratory personnel can affect experimental results.

[0004] Therefore, there is an urgent need for a reaction control system for automating NGS library construction. Summary of the Invention

[0005] The purpose of this invention is to provide a reaction control system for automated NGS library construction to solve the above-mentioned problems.

[0006] To achieve the above objectives, the present invention provides the following solution: A reaction control system for automated NGS library construction, used to match a reaction apparatus for library construction, the reaction apparatus including reaction orifices, and the reaction control system comprising: Base plate; The motion module is mounted on the base plate; The upper plate is directly or indirectly connected to the motion end of the motion module; The nucleic acid extraction module is mounted on the upper plate; The nucleic acid fragmentation module is located on the upper plate. Multiple first driving components are disposed on the upper plate, and each of the multiple first driving components is configured in a one-to-one correspondence with the nucleic acid extraction module and the nucleic acid fragmentation module; the motion module and the first driving components are capable of moving the nucleic acid extraction module and the nucleic acid fragmentation module in different directions to drive the nucleic acid extraction module and the nucleic acid fragmentation module to connect with the corresponding reaction wells; The library amplification module is mounted on the base plate and provides the temperature required for the amplification reaction to the corresponding reaction wells; The processor is electrically connected to at least the motion module, the first driving component, the nucleic acid extraction module, the nucleic acid fragmentation module, and the library amplification module.

[0007] Optionally, the nucleic acid extraction module includes: The first lower platform is fixedly connected to the moving end of one of the first drive components; The first upper platform is connected to the side of the first lower platform away from the first drive assembly by multiple bolts, and the distance between the first upper platform and the first lower platform is adjustable. A first elastic element is disposed between the first lower platform and the first upper platform, and the two ends of the first elastic element abut against the first lower platform and the first upper platform, respectively. A first heating stage is fixedly connected to the side of the first upper stage away from the first lower stage. A first temperature sensor is fixedly installed on the first heating stage. The first temperature sensor is electrically connected to the processor. The first heating stage is correspondingly set with a reaction port of the reaction device. A first heating element is disposed between the first heating platform and the first upper platform. The first heating element is thermally conductive to the first heating platform and insulated from the first upper platform. The first heating element is electrically connected to the processor. A high-temperature resistant permanent magnet is obliquely mounted on the side inside the first heating platform and fixed by adhesive or potting.

[0008] Optionally, the nucleic acid fragmentation module includes: The second lower platform is connected to the moving end of one of the first drive components; The second heating platform is provided corresponding to one of the reaction holes of the reaction device; An ultrasonic component is provided to the reaction orifice corresponding to the second heating stage with the ultrasonic wave required for fragmentation, and the ultrasonic component is electrically connected to the processor. The second elastic element is located between the second lower platform and the ultrasonic component; A fourth elastic element is located between the second heating stage and the ultrasonic component.

[0009] Optionally, the ultrasound assembly includes a first ultrasound fixation component, a second ultrasound fixation component, and an ultrasound transducer; the nucleic acid fragmentation module further includes a second heating element and a first guiding component; The second elastic element is sleeved on one end of the first drive assembly that protrudes from the second lower platform. The first ultrasonic fixing member is sleeved on one end of the moving end of the first driving component that protrudes from the second lower platform. The two ends of the second elastic member abut against the second lower platform and the first ultrasonic fixing member, respectively. The side of the first ultrasonic fixing member away from the second elastic member is provided with a second upper platform. The second upper platform is threadedly connected to the moving end of the first driving component. The second ultrasonic fixation member is fixedly connected to the first ultrasonic fixation member; The second heating stage is fixedly connected to the first ultrasonic fixation member; a second temperature sensor is provided on the second heating stage, and the second temperature sensor is electrically connected to the processor; The second heating element is disposed between the first ultrasonic fixation member and the second heating stage. The second heating element is thermally conductive to the second heating stage and insulated from the second upper stage surface. The second heating element is electrically connected to the processor. The fourth elastic element is disposed between the first ultrasonic fixation element and the second heating stage, and the two ends of the fourth elastic element abut against the first ultrasonic fixation element and the second heating stage respectively. The ultrasonic transducer is fixedly installed between the first ultrasonic fixture and the second ultrasonic fixture. The top end of the ultrasonic transducer passes through the second ultrasonic fixture / second heating platform / second heating plate and is threadedly connected to an ultrasonic converter head. The ultrasonic converter head is correspondingly set with a reaction hole of the reaction device. The ultrasonic transducer is electrically connected to the processor. The first guide assembly includes a first slide rail and a first slider slidably connected to the first slide rail. The first slide rail is fixed to the upper plate, and the first ultrasonic fixation member is fixed to the first slider. The first slider is located between the upper plate and the first ultrasonic fixation member.

[0010] Optionally, the first driving component includes: A first push rod linear motor is fixedly connected to the upper plate. The moving end of the first push rod linear motor is fixedly connected to the first lower platform / second lower platform. The first push rod linear motor is electrically connected to the processor. The second photoelectric sensor is fixed to the lower plate and is correspondingly disposed to the moving end of the first push rod linear motor. The second photoelectric sensor is disposed at the end of the first push rod linear motor away from the first lower platform / second lower platform, and the second photoelectric sensor is electrically connected to the processor.

[0011] Optionally, the library expansion module includes: The second drive component is fixed relative to the base plate and electrically connected to the processor; A stage assembly is connected to the moving end of the second drive assembly. The stage assembly includes a stage, a semiconductor cooling chip, and a heat dissipation assembly. The second drive assembly can drive the stage assembly to move so that the stage can dock with the corresponding reaction hole. The thermoelectric cooler is electrically connected to the processor. The thermoelectric cooler has a cold end and a hot end, one of which faces the worktable, and the other of which faces the heat dissipation assembly.

[0012] Optionally, the workbench includes a third lower table surface, a third upper table surface, and a third heating table; the heat dissipation assembly includes a heat sink fixing plate and a heat sink; and the document expansion module further includes a third elastic element, a telescopic air duct, a ventilation duct, a first heat insulation pad, a heating cover, and a third temperature sensor; wherein the third lower table surface is fixed to the moving end of the second drive assembly. The third upper platform is connected to the third lower platform by multiple bolts, and the distance between the third lower platform and the third upper platform is adjustable; The third elastic member is disposed between the third lower platform and the third upper platform, and the two ends of the third elastic member abut against the third lower platform and the third upper platform, respectively. The radiator mounting plate is fixedly connected to the third upper platform; The heat sink is fixedly connected to the heat sink mounting plate, and a fan is fixedly installed on one side of the heat sink. The fan is electrically connected to the processor. The telescopic duct is fixed at both ends to the radiator fixing plate and the base plate, respectively. The ventilation duct is fixedly installed on the side of the base plate away from the telescopic duct; The first heat insulation pad is placed between the base plate and the ventilation duct; The third heating platform is disposed on the heat sink, and the third heating platform is disposed corresponding to a reaction hole of the reaction device. A third temperature sensor is disposed on the third heating platform, and both the third heating platform and the third temperature sensor are electrically connected to the processor. The semiconductor cooling chip is disposed between the heat sink and the third heating stage, and the third heating stage and the semiconductor cooling chip are covered with a second heat insulation pad on their outer sides. The heating cover is fixedly connected to the radiator, and the side of the heating cover facing the radiator abuts against the third heating platform.

[0013] Optionally, the second driving component includes: The second push rod linear motor is fixed to the base plate by a motor mounting plate, and the second push rod linear motor is electrically connected to the processor; The second guide assembly includes a second slide rail and a second slider slidably connected to the second slide rail. The second slide rail is fixed to the base plate, and the second slider is slidably fixed to the side of the third lower platform away from the linear motor. A third photoelectric sensor is fixedly mounted on the lower plate, and the third photoelectric sensor is disposed corresponding to the third lower platform. The third photoelectric sensor is electrically connected to the processor.

[0014] Preferably, the motion module includes: A lead screw assembly includes a lead screw, a lead screw fixing structure, and a power motor. The lead screw is rotatably connected to the lead screw fixing structure. One end of the lead screw is coaxially fixed to the power motor. The power motor is fixed to the lead screw fixing structure. The lead screw fixing structure is fixed to the base plate. The power motor is electrically connected to the processor. The lower plate is threadedly connected to the lead screw, and the lower plate is slidably connected to the base plate and fixedly connected to the upper plate; A first photoelectric sensor is fixed to the base plate and correspondingly disposed to the lower plate, and the first photoelectric sensor is electrically connected to the processor.

[0015] Preferably, the first heating element includes: plate body; Multiple resistors are fixedly connected to the plate, and the multiple resistor arrays are distributed; The wiring terminal is fixed to the board and electrically connected to the plurality of resistors; the wiring terminal is electrically connected to the processor. A thermal fuse is connected in series between any two adjacent resistors.

[0016] Compared with the prior art, the present invention has the following advantages and technical effects: 1) This invention proposes a reaction control system for automated NGS library construction, which, in conjunction with the reaction apparatus, can realize the automation of NGS library construction; 2) The reaction control structure is simple; each module is assembled individually and then installed in its corresponding position to form the main tooling. The modular design facilitates adjustment; modules can be added or removed as needed, making installation and transportation convenient and flexible.

[0017] 3) The library amplification module, nucleic acid extraction module, and nucleic acid fragmentation module move up and down with precise displacement. They have elastic damping devices that compress the elastic components before contacting the reaction device to prevent rigid collisions. The elastic components adjust their positions adaptively to reduce errors. The heating stage has a groove structure that matches the reaction device, allowing the modules and the reaction device to fit more tightly under the force of the elastic components, resulting in better reaction effects.

[0018] 4) The library expansion module uses a heat sink + fan side cooling method to accelerate the cooling speed and shorten the response time. Attached Figure Description

[0019] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly described below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort. Figure 1 This is a block diagram of a library construction system in some embodiments of the present invention; Figure 2 This is a front view of the reaction control system in some embodiments of the present invention; Figure 3 This is a front view of the reaction control system after removing the motion module and the base plate in some embodiments of the present invention; Figure 4 This is a front view of the first heating element in some embodiments of the present invention; Figure 5 This is a partial structural diagram of the library expansion module in some embodiments of the present invention; The components are as follows: 1. Base plate; 2. First lower platform; 3. First upper platform; 4. Lead screw; 5. Lower plate; 6. Upper plate; 7. First elastic element; 8. First heating element; 9. First slider; 10. First heating stage; 11. First photoelectric sensor; 12. Second photoelectric sensor; 13. First temperature sensor; 14. First push rod linear motor; 15. Second lower platform; 16. Second elastic element; 17. Second upper platform; 18. First ultrasonic fixing element; 19. Second ultrasonic fixing element; 20. Ultrasonic transducer; 21. Ultrasonic converter head; 22. Second push rod linear motor; 23. Motor fixing plate; 24. Second slider; 25. Third photoelectric sensor; 26. Third lower platform. ; 27. Third elastic element; 28. Third upper platform; 29. ​​Heat sink fixing plate; 30. Heat sink; 31. Fan; 32. Semiconductor cooling chip; 33. Second heat insulation pad; 34. Heating cover; 35. Third heating stage; 36. Third temperature sensor; 37. High temperature resistant permanent magnet; 38. Second heating stage; 39. Second temperature sensor; 40. Second heating element; 41. Fourth elastic element; 42. Telescopic air duct; 43. Ventilation duct; 44. First heat insulation pad; 801. Wiring terminal; 802. Resistor; 803. Temperature fuse; 100. Nucleic acid extraction module; 200. Nucleic acid fragmentation module; 300. Library amplification module; 310. Second drive component. Detailed Implementation

[0020] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0021] See Figure 1 , Figure 1 The library construction system is illustrated. In this embodiment, the reaction control system is matched with the reaction apparatus, and the two work together to achieve library construction, thus automating NGS library construction. The reaction apparatus is equipped with reaction orifices and a reagent transfer mechanism. Figure 1 The reaction apparatus motion modules 1, 2, and 3 control the reagent transfer mechanism to automatically perform operations such as reagent aspiration, transfer, and even mixing within the reaction apparatus. The reaction apparatus provides a closed environment for the reaction operation, isolating it from the external environment and preventing contamination of reagents, samples, and reaction products during library construction.

[0022] The reaction wells are used to hold reagents, samples, etc. The reaction wells are connected to the internal sealed space of the reaction apparatus, but not to the external space. The nucleic acid extraction module 100, nucleic acid fragmentation module 200, and library amplification module 300 mentioned below are respectively connected to their corresponding reaction wells, which can be understood as contacting the outer wall of the well. In this way, the reaction control system can provide the necessary reaction conditions, such as temperature, magnetic separation, and ultrasound, for nucleic acid extraction, nucleic acid fragmentation, and library amplification operations while keeping the reaction apparatus sealed.

[0023] The processor can be connected to both the reaction apparatus and the reaction control system to coordinate their operation and better automate library amplification.

[0024] The reaction control system is used in conjunction with the reaction apparatus and can automatically perform library construction operations according to a pre-set, computer-readable program. Once the system is started, almost no human intervention is required, which significantly reduces manual operation and thus reduces the impact of improper operation by experimenters on experimental results, thereby improving the degree of automation of library construction.

[0025] In some implementations, the reaction control system is located below the reaction apparatus. During library construction, the position of the reaction apparatus can remain unchanged. The nucleic acid extraction module 100 and the nucleic acid fragmentation module 200, under the action of the motion module (mentioned below), automatically move to below the target reaction well according to the processor's instructions and dock with the target reaction well. Of course, the nucleic acid extraction module 100 and the nucleic acid fragmentation module 200 can move to the same reaction well at different times. When a corresponding reaction operation is required, after ensuring that each module (including the acid extraction module 100, the nucleic acid fragmentation module 200, and the library amplification module 300) is below the corresponding reaction well, the current coordinates of each module remain unchanged, and the corresponding module is raised using the driving component until it contacts the corresponding reaction well. In the implementation shown in the figures of this application, the aforementioned coordinates can be understood as coordinates on the horizontal plane.

[0026] The nucleic acid extraction module 100 can provide the required temperature and even the magnetic force required for magnetic separation in the nucleic acid extraction operation.

[0027] The fragmentation module 200 can provide the necessary ultrasound for nucleic acid fragmentation operations, and even meet heating requirements.

[0028] Typically, multiple different temperatures are required for the amplification reaction, such as the denaturation temperature, annealing temperature, and renaturation temperature—three key temperatures—and these temperatures need to be cycled multiple times. The library amplification module 300 utilizes a combination of a thermoelectric cooler 32 and a heat dissipation component to more efficiently meet the cyclic temperature requirements of the amplification reaction. For example, when a temperature increase is required under the processor's instruction, the side of the thermoelectric cooler 32 (described further below) facing the reaction aperture becomes the hot end, and the side facing the heat dissipation component becomes the cold end. With the heat dissipation of the heat dissipation component, the thermoelectric cooler 32 can quickly provide the required temperature to the reaction aperture. When a temperature decrease is required, the side of the thermoelectric cooler 32 facing the reaction aperture is adjusted to the cold end, quickly lowering the temperature to the required level. Based on the Peltier effect, the switching between the hot and cold ends of the thermoelectric cooler 32 can be achieved by reversing the current, eliminating the need to reverse the thermoelectric cooler 32, making the implementation simpler. Moreover, this temperature-changing method allows for rapid switching to different temperatures without moving the library amplification module 300, improving the efficiency of switching between different temperatures and shortening the reaction time. A single library amplification module 300 simultaneously meets multiple temperature requirements, further improving the integration of the reaction control system. Furthermore, the relatively fixed placement of the library amplification module 300 below a specific reaction well optimizes the layout of the reaction control system. It eliminates the need for a motion module to facilitate the movement of the library amplification module 300 relative to the reaction apparatus, resulting in a more compact and simpler system structure and cost savings.

[0029] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, the present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments.

[0030] Reference Figures 1 to 4 This invention discloses a reaction control system for automated NGS library construction, used to match a reaction apparatus for library construction. The reaction apparatus includes reaction orifices, and the reaction control system includes: Base plate 1; The motion module is mounted on the base plate 1; The upper plate 6 is directly or indirectly connected to the motion end of the motion module; Nucleic acid extraction module 100 is mounted on the upper plate 6; The preferred number of nucleic acid extraction modules 100 is one.

[0031] Nucleic acid fragmentation module 200 is installed on the upper plate 6. Multiple first driving components are set on the upper plate 6, and each of the multiple first driving components corresponds to the nucleic acid extraction module and the nucleic acid fragmentation module. The library expansion module 300 is mounted on the base plate 1.

[0032] The reaction apparatus is provided with multiple reaction wells, which are adapted to the nucleic acid extraction module 100, the nucleic acid fragmentation module 200, the library amplification module 300, and the motion module. The reaction apparatus is electrically connected to a processor, which is electrically connected to the first driving component, the nucleic acid extraction module 100, the nucleic acid fragmentation module 200, and the library amplification module 300.

[0033] The reaction device and processor are existing technologies, and those skilled in the art can select / set them according to their own needs, which will not be elaborated here.

[0034] The motion module and the first driving component can move the nucleic acid extraction module 100 and the nucleic acid fragmentation module 200 in different directions to engage the nucleic acid extraction module 100 and the nucleic acid fragmentation module 200 with the corresponding reaction wells. The motion directions of the motion module and the first driving component are approximately perpendicular.

[0035] See Figure 2 The base plate 1 can be considered as a vertical plate perpendicular to the horizontal plane. The motion module can drive the upper plate 6 to move horizontally relative to the base plate 1 below the reaction device to locate the target reaction hole. After locating the target reaction hole, the motion module stops moving, and the first driving component drives the corresponding nucleic acid extraction module 100 or nucleic acid fragmentation module 200 to move vertically relative to the base plate 1, so that the nucleic acid extraction module 100 or nucleic acid fragmentation module 200 contacts the target reaction hole (or "corresponding reaction hole"). Alternatively, as needed, the first driving component can also drive the corresponding nucleic acid extraction module 100 or nucleic acid fragmentation module 200 to descend vertically until the nucleic acid extraction module 100 or nucleic acid fragmentation module 200 resets.

[0036] See Figure 2 The upper plate 6 is roughly parallel to the bottom plate 1 and is located in front of the bottom plate 1 (the direction facing the reader is front, and the direction facing the paper and away from the reader is back).

[0037] Since both the nucleic acid extraction module 100 and the nucleic acid fragmentation module 200 are mounted on the upper plate 6, one motion module can drive multiple modules, including the nucleic acid extraction module 100 and the nucleic acid fragmentation module 200, to move synchronously using the upper plate 6. This layout is more rational and balances economy and practicality. Multiple mounting positions can be reserved on the upper plate 6 to accommodate the addition of the nucleic acid extraction module 100 and / or the nucleic acid fragmentation module 200. Alternatively, both the upper plate 6 and each module can be detachable, allowing for the addition or removal of modules. This enriches the system's application scenarios.

[0038] Based on the foregoing description, the library amplification module 300 has a heating function to provide the required temperature for the amplification reaction in the corresponding reaction wells. In a preferred implementation, the library amplification module 300 also has a heat dissipation function (described in detail below), such as by adding a heat dissipation component to the library amplification module 300. This heat dissipation component can accelerate cooling and shorten the time required to switch from a higher temperature to a lower temperature. A single library amplification module 300 can meet the cycling requirements between multiple temperatures, improving the efficiency of the library amplification reaction.

[0039] In this application's embodiments, "nucleic acid" includes, but is not limited to, DNA and RNA. For example, Figure 1 Two DNA extraction modules (i.e., DNA extraction module 1 and DNA extraction module 2) and one DNA fragmentation module are illustrated.

[0040] In some examples, the motion module is fixedly mounted on the base plate 1. The upper plate 6 is connected to the lower plate 5, and the lower plate 5 is fixedly connected to the motion end of the motion module.

[0041] The nucleic acid extraction module has been further optimized and includes: The first lower platform 2 is fixedly connected to the moving end of one of the first drive components; The first upper platform 3 is connected to the side of the first lower platform 2 away from the first drive assembly by multiple bolts, and the distance between the first upper platform 3 and the first lower platform 2 is adjustable; Mounting grooves are provided on both sides of the first upper platform 3 and the first lower platform 2 that are adjacent to each other. The first elastic element 7 is disposed between the first lower platform 2 and the first upper platform 3, and the two ends of the first elastic element 7 abut against the first lower platform 2 and the first upper platform 3 respectively; the first elastic element 7 is located in the two mounting grooves. The first heating stage 10 is fixedly connected to the side of the first upper stage 3 away from the first lower stage 2. A first temperature sensor 13 is fixedly installed on the first heating stage 10. The first temperature sensor 13 is electrically connected to the processor. The first heating stage 10 is set to correspond to a reaction port of the reaction device. The first heating element 8 is disposed between the first heating platform 10 and the first upper platform 3. The first heating element 8 is heat-conducting with the first heating platform 10, and the first heating element 8 is insulated from the first upper platform 3. The first heating element 8 is electrically connected to the processor.

[0042] Multiple bolts are slidably connected within the first lower platform 2 and the first upper platform 3. The multiple bolts are evenly spaced circumferentially. The first upper platform 3 and the first lower platform 2 are supported by the first elastic element 7 to prevent the reaction hole from rigidly contacting the device of the present invention during the reaction process, which would cause damage to the reaction hole / the device. The first temperature sensor 13 is installed in a reserved hole on the first heating platform 10. A high-temperature resistant permanent magnet 37 is fixedly installed in the reserved hole on the side of the first temperature sensor 13. The smooth surfaces of the first heating platform 10 and the first heating element 8 are coated with thermal grease. The smooth surfaces of the first heating platform 10 and the first heating element 8 are in close contact. The first heating platform 10 is placed in the groove on the first upper platform 3 and then fixed by bolts. The gap between the first heating element 8 and the first upper platform 3 is sealed with insulating glue.

[0043] The first elastic element 7 can be a spring, a sheet, or even an elastic rubber component.

[0044] Under the driving action of the first driving component, when the first heating stage 10 rises to dock with the reaction hole, the first elastic element 7 can alleviate the damage to the components caused by hard contact during the docking process. The elasticity provided by the first elastic element 7 can also increase the tightness of the fit between the first heating stage 10 and the outer wall of the reaction hole, ensuring the heating or magnetic separation effect.

[0045] The first temperature sensor 13, in conjunction with the processor, can automatically, promptly, and accurately monitor the reaction temperature, ensuring reaction quality. The top of the first heating stage 10 has a groove that matches the shape of the reaction orifice wall, allowing the reaction orifice to be inserted into the groove during docking. Similarly, the second heating stage 38 and the third heating stage 35, mentioned below, can also each have grooves matching the reaction orifice.

[0046] See Figure 3 The scheme has been further optimized, and the nucleic acid fragmentation module 200 includes: The second lower platform 15 is connected to the moving end of one of the first drive components; The second heating stage 38 is set in correspondence with one of the reaction holes of the reaction device; An ultrasonic component is provided with the ultrasonic waves required for fragmentation to the reaction orifice corresponding to the second heating stage 38. The ultrasonic component is electrically connected to the processor. The second elastic element 16 is located between the second lower platform 15 and the ultrasonic component; The fourth elastic element 41 is located between the second heating stage 38 and the ultrasonic component.

[0047] The ultrasonic waves provided by the ultrasonic component are used to break nucleic acids into short fragments. The ultrasonic component can also be used to mix magnetic beads or reagents. During the ultrasonic process, the ultrasonic component vibrates; the second elastic element 16 absorbs the vibration energy between the ultrasonic component and the second lower stage 15, and the fourth elastic element 41 absorbs the vibration energy between the second heating stage and the ultrasonic component. Furthermore, the fourth elastic element 41 can mitigate component damage caused by hard contact during the docking process between the second heating stage 38 and the reaction well, increase the tightness of the fit between the first heating stage 10 and the outer wall of the reaction well, and ensure the ultrasonic effect.

[0048] The second elastic element 16 and the fourth elastic element 41 can both be springs, or they can each be independently made of sheet metal or elastic rubber parts.

[0049] In some embodiments, the ultrasound component includes a first ultrasound fixation member 18, a second ultrasound fixation member 19, and an ultrasound transducer 20; the nucleic acid fragmentation module 200 further includes a second heating element 40 and a first guide component. The second elastic element 16 is sleeved on one end of the moving end of the first drive assembly that protrudes from the second lower platform 15; The first ultrasonic fixing member 18 is sleeved on one end of the moving end of the first driving component that protrudes from the second lower platform 15. The two ends of the second elastic member 16 abut against the second lower platform 15 and the first ultrasonic fixing member 18 respectively. The side of the first ultrasonic fixing member 18 away from the second elastic member 16 is provided with a second upper platform 17. The second upper platform 17 is threadedly connected to the moving end of the first driving component. The second ultrasonic fixation member 19 is fixedly connected to the first ultrasonic fixation member 18; The second heating stage 38 is fixedly connected to the first ultrasonic fixation member 18; a second temperature sensor 39 is provided on the second heating stage 38, and the second temperature sensor 39 is electrically connected to the processor. The second heating element 40 is disposed between the first ultrasonic fixing member 18 and the second heating stage 38. The second heating element 40 and the second heating stage 38 are heat-conductingly disposed. The second heating element 40 and the second upper stage 38 are insulated and heat-insulated. The second heating element 40 is electrically connected to the processor. The fourth elastic member 41 is disposed between the first ultrasonic fixation member 18 and the second heating stage 38, and the two ends of the fourth elastic member 41 abut against the first ultrasonic fixation member 18 and the second heating stage 38 respectively. The ultrasonic transducer 20 is fixedly installed between the first ultrasonic fixture 18 and the second ultrasonic fixture 19. The top end of the ultrasonic transducer 20 passes through the second ultrasonic fixture 19 / second heating platform 38 / second heating plate 40 and is threadedly connected to an ultrasonic converter head 21. The ultrasonic converter head 21 is correspondingly set with a reaction hole of the reaction device. The ultrasonic transducer 20 is electrically connected to the processor. The first guide assembly includes a first slide rail and a first slider 9 slidably connected to the first slide rail. The first slide rail is fixed to the upper plate 6. The first ultrasonic fixing member 18 is fixed to the first slider 9. The first slider 9 is located between the upper plate 6 and the first ultrasonic fixing member 18.

[0050] The processor can independently control the second heating element 40 and the ultrasonic transducer 20, allowing them to turn on or off independently. After the segmentation operation in the corresponding reaction hole is completed, the corresponding first driving component can be controlled to lower the second heating stage 38, separating it from the reaction hole.

[0051] See Figure 3 The first ultrasonic fixation member 18 extends to the side of the second lower platform 15, so that the ultrasonic transducer 20, the second heating stage 38, the second heating plate 40, the fourth elastic member 41, etc. are located in the side space of the second lower platform 15 without occupying the space above the second lower platform 15. This can reduce the height of the nucleic acid fragmentation module 200 and move the second heating plate 40 away from the first driving component below the second lower platform 15, reducing the impact on the first push rod linear motor 14 in the first driving component.

[0052] Further optimization of the solution, the first driving component includes: The first push rod linear motor 14 is fixedly connected to the upper plate 6. The moving end of the first push rod linear motor 14 is fixedly connected to the first lower platform 2 / second lower platform 15. The first push rod linear motor 14 is electrically connected to the processor. The second photoelectric sensor 12 is fixed on the lower plate 5. The second photoelectric sensor 12 is correspondingly set to the moving end of the first push rod linear motor 14. The second photoelectric sensor 12 is set at the end of the first push rod linear motor 14 away from the first lower platform 2 / second lower platform 15. The second photoelectric sensor 12 is electrically connected to the processor.

[0053] The second photoelectric sensor 12 can be used as a position switch to monitor the position of the first push rod linear motor 14 and convert the physical position signal into a recognizable electrical or digital signal to achieve automated control or safety protection.

[0054] The library expansion module 300, further optimized, includes: The second drive component 310 is fixed relative to the base plate 1 and electrically connected to the processor; The stage assembly is connected to the moving end of the second drive assembly 310. The stage assembly includes a stage, a thermoelectric cooler 32, and a heat dissipation assembly. The second drive assembly 310 can drive the stage assembly to move so that the stage aligns with the corresponding reaction hole. The thermoelectric cooler 32 is electrically connected to the processor. The thermoelectric cooler 32 has a cold end and a hot end, one of which faces the stage and the other of which faces the heat dissipation assembly.

[0055] The thermoelectric cooler 32 can be in direct or indirect contact with the corresponding reaction wells. When the reaction wells require heating to achieve a higher temperature, the side of the thermoelectric cooler 32 facing the stage becomes the hot end to heat the reaction wells, raising the temperature inside the wells to the required higher temperature. When the reaction enters the next stage and a lower temperature is required, the side of the thermoelectric cooler 32 facing the stage is adjusted to become the cold end, allowing the temperature of the reaction wells to drop to the required lower temperature. As mentioned earlier, the heat dissipation assembly can quickly dissipate heat, preventing the side of the thermoelectric cooler 32 away from the stage from becoming too cold or too hot. In this way, it can quickly respond to and switch to the problems required for the amplification reaction, improving reaction efficiency.

[0056] Compared to other heating methods such as resistance heating and infrared heating, the semiconductor cooling chip 32 can more accurately and timely meet the needs of multiple temperature cycle switching in the library amplification reaction.

[0057] In some embodiments, the workbench includes a third lower table surface 26, a third upper table surface 28 and a third heating table 35, the heat dissipation assembly includes a radiator fixing plate 29 and a radiator 30, and the library expansion module 300 also includes a third elastic element 27, a telescopic air duct 42, a ventilation duct 43, a first heat insulation pad 44, a heating cover 34 and a third temperature sensor 36. The third lower platform 26 is fixedly connected to the moving end of the second drive assembly 310; The third upper platform 28 is connected to the third lower platform 26 by multiple bolts, and the distance between the third lower platform 26 and the third upper platform 28 is adjustable; The third elastic member 27 is disposed between the third lower platform 26 and the third upper platform 28, and the two ends of the third elastic member 27 abut against the third lower platform 26 and the third upper platform 28 respectively. Mounting grooves are provided on the adjacent surfaces of the third lower platform 26 and the third upper platform 28, and the third elastic element 27 is located in the two mounting grooves. The radiator mounting plate 29 is fixedly attached to the third upper platform 28; The heat sink 30 is fixedly connected to the heat sink mounting plate 29, and a fan 31 is fixedly installed on one side of the heat sink 30. The fan 31 is electrically connected to the processor. The two ends of the telescopic duct 42 are fixedly connected to the radiator fixing plate 29 and the base plate 1, respectively. The ventilation duct 43 is fixedly installed on the side of the base plate 1 away from the telescopic duct 42; The first heat insulation pad 44 is disposed between the base plate 1 and the ventilation duct 43; The third heating platform 35 is mounted on the heat sink 30. The third heating platform 35 is corresponding to a reaction port of the reaction device. The third heating platform 35 is equipped with a third temperature sensor 36. Both the third heating platform 35 and the third temperature sensor 36 are electrically connected to the processor. The thermoelectric cooler 32 is contacted between the heat sink 30 and the third heating platform 35, with the hot end of the thermoelectric cooler 32 facing the heat sink 30. The third heating platform 35 and the outer side of the thermoelectric cooler 32 are covered with a second heat insulation pad 33. The thermoelectric cooler 32 is electrically connected to the processor. The heating cover 34 is fixedly connected to the radiator 30, and the side of the heating cover 34 facing the radiator 30 abuts against the third heating platform 35.

[0058] The third temperature sensor 36 is located in the reserved hole on the third heating platform 35. Thermal paste is applied to both sides of the thermoelectric cooler 32, with one end in contact with the heat sink 30 and the other end in contact with the third heating platform 35. The second heat insulation pad 33 is wrapped around the thermoelectric cooler 32 and is higher than the thermoelectric cooler 32. The heating cover 34 presses down on the third heating platform 35 and is fastened to the heat sink 30 with bolts. At this time, the second heat insulation pad 33 is compressed, and the thermoelectric cooler 32 is in closer contact with the third heating platform 35. Considering the airflow direction of the entire system, the fan 31 is fixed to the side of the heat sink 30.

[0059] The third elastic element 27 can be a spring, a sheet, or an elastic rubber component.

[0060] Under the driving action of the second driving component 310, when the third heating stage 35 rises to dock with the reaction hole, the third elastic element 27 can alleviate the damage to the components caused by hard contact during the docking process. The elasticity provided by the third elastic element 27 can also increase the tightness of the fit between the third heating stage 35 and the outer wall of the reaction hole, ensuring the heat exchange effect between the semiconductor cooling chip 32 and the reaction hole.

[0061] See Figure 5 The heat dissipated by the heat dissipation component is discharged through the air duct, which includes the telescopic air duct 42 and the ventilation duct 43. The ventilation duct 43 is located on the rear side of the base plate 1, and the other components of the library expansion module 300 are basically located on the front side of the base plate 1. This layout can keep the heat dissipated by the heat sink 30 away from most of the components of the library expansion module 300, at least reducing the impact of the dissipated heat on the second drive component 310 and the third heating platform 35.

[0062] Figure 2An exemplary subunit of the reaction control system is shown, which mainly consists of a base plate 1, a motion module, a top plate nucleic acid extraction module 100, and a nucleic acid fragmentation module 200. The reaction control system may include one subunit or two or more subunits. The ventilation duct 43 located behind the base plate 1 can also reduce physical interference or thermal impact on other subunits when multiple subunits are combined.

[0063] For the same subunit, the number of modules is not limited to Figure 2 Each of the above can be set to one, and two, three or more can be set independently.

[0064] Since the heat dissipation components can be raised and lowered synchronously with the third heating platform 35, and the ventilation duct 43 is fixed to the base plate 1, the telescopic air duct 42 can better adapt to the movement of components such as the heat dissipation components and the third heating platform 35 relative to the base plate 1.

[0065] The retractable duct 42 can be a flexible hose with a retractable allowance or a corrugated pipe, but is not limited to these.

[0066] The ventilation duct 43 can extend downward to the bottom of the base plate 1, allowing the heat or cold emitted by the fan 31 to flow out from the bottom of the base plate 1, further reducing the impact on other components.

[0067] Further optimization of the scheme, the second drive component 310 includes: The second push rod linear motor 22 is fixed to the base plate 1 by the motor fixing plate 23, and the second push rod linear motor 22 is electrically connected to the processor. The second guide assembly includes a second slide rail and a second slider 24 slidably connected to the second slide rail. The second slide rail is fixedly connected to the moving end of the second push rod linear motor 22, and the second slider 24 is fixedly connected to the third lower platform 26. The third photoelectric sensor 25 is fixedly connected to the base plate 1. The third photoelectric sensor 25 is correspondingly set with the third lower platform 26. The third photoelectric sensor 25 is electrically connected to the processor.

[0068] The solution has been further optimized, and the motion module includes: The lead screw assembly includes a lead screw 4, a lead screw fixing structure, and a power motor. The lead screw 4 is rotatably connected to the lead screw fixing structure. One end of the lead screw 4 is coaxially fixed to the power motor. The power motor is fixed to the lead screw fixing structure. The lead screw fixing structure is fixed to the base plate 1. The power motor is electrically connected to the processor. The lower plate 5 is threadedly connected to the lead screw 4. The lower plate 5 is slidably connected to the base plate 1 and fixedly connected to the upper plate 6. The first photoelectric sensor 11 is fixed on the base plate 1 and is correspondingly set with the lower plate 5. The first photoelectric sensor 11 is electrically connected to the processor.

[0069] The design has been further optimized, and the first heating element 8 includes: plate body; Multiple resistors 802 are fixed to the board, and the multiple resistors 802 are distributed in an array; Terminal 801 is fixed to the board and electrically connected to multiple resistors 802. Terminal 801 is also electrically connected to the processor. The thermal fuse 803 is connected in series between any two adjacent resistors 802.

[0070] The 803 thermal fuse melts when the temperature exceeds the temperature threshold, thus stopping heating and ensuring heating safety.

[0071] The working process of the reaction control system in this application embodiment includes: Reset: The power motor drives the lead screw 4 to rotate, which in turn drives the lower plate 5 to move along the length of the lead screw 4. When the lead screw 4 moves to the set position, the first photoelectric sensor 11 is triggered. At this time, the reset is completed and the power motor stops working. Nucleic acid fragmentation was performed on the reaction wells: The power motor drives the lead screw 4 to rotate, which in turn drives the upper plate 6 to move through the lower plate 5, so that the ultrasonic converter head 21 moves to the reaction hole. The first push rod linear motor 14 drives the second lower platform 15 to move, which in turn drives the ultrasonic converter head 21 to contact the reaction hole. At this time, the second elastic element 16 is compressed, the first push rod linear motor 14 stops working, and the ultrasonic transducer 20 is turned on. After the ultrasonic treatment is completed, the first push rod linear motor 14 drives the second lower platform 15 to return to the original position. Nucleic acid extraction was performed on the reaction wells: The reaction hole is pre-filled with reaction reagents. The power motor drives the lead screw 4 to rotate, which in turn drives the upper plate 6 to move through the lower plate 5, so that the first heating stage 10 moves to the bottom of the reaction hole. At this time, the first push rod linear motor 14 drives the first lower stage 2 to move, which in turn drives the first heating stage 10 to contact the reaction hole. At this time, the first elastic element 7 is compressed, the first push rod linear motor 14 stops working, the first heating plate 8 heats up, and incubation is carried out. Then, magnetic separation is performed, the liquid is sucked out and put into the waste liquid pool, the reaction reagent is sucked out and washed, and this process is repeated many times until the reaction is completed. Then, the first push rod linear motor 14 drives the first lower stage 2 to return to the original position. Library amplification reaction was performed on the reaction wells: The second push rod linear motor 22 drives the third lower platform 26 to move to the third heating platform 35 and contact the reaction hole. At this time, the third elastic element 27 is compressed, the second push rod linear motor 22 stops moving, and the fan 31 and the semiconductor cooling chip 32 are turned on, so that the temperature of the third heating platform 35 cycles between the denaturation temperature, annealing temperature and resetting temperature. After the cycle is set a number of times, the temperature is reduced to 4°C.

[0072] In summary, the reaction control system of this application embodiment has a simple structure. Each module can be assembled individually and installed in its corresponding position to form the main body of the reaction control system. The modular design facilitates adjustment, and each module can be added or removed as needed. It is convenient for installation and transportation and has flexibility. The library amplification module 300, nucleic acid extraction module 100, and nucleic acid fragmentation module 200 have precise vertical displacement and are equipped with spring shock absorption devices. When in contact with the reaction device, the springs are compressed first to prevent rigid collisions with the reaction device. The springs self-adjust their positions to reduce errors. The library amplification module 300 uses a heat sink 30 + fan 31 for side cooling to accelerate the cooling rate and shorten the reaction time.

[0073] In the embodiments of this application, other structures required to achieve automated operation, such as controllers, memory, and communication systems, can all adopt solutions known to those skilled in the art, and will not be described in detail here.

[0074] In the description of this invention, it should be understood that the terms "longitudinal", "lateral", "up", "down", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings, and are only for the convenience of describing this invention, and are not intended to indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation, and therefore should not be construed as a limitation of this invention.

[0075] The embodiments described above are merely preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Various modifications and improvements made by those skilled in the art to the technical solutions of the present invention without departing from the spirit of the present invention should fall within the protection scope defined by the claims of the present invention.

Claims

1. A reaction control system for automated NGS library construction, used to match a reaction apparatus for library construction, the reaction apparatus including reaction orifices, characterized in that, include: Base plate (1); The motion module is mounted on the base plate (1); The upper plate (6) is directly or indirectly connected to the motion end of the motion module; A nucleic acid extraction module (100) is mounted on the upper plate (6); A nucleic acid fragmentation module (200) is disposed on the upper plate (6). Multiple first driving components are disposed on the upper plate (6), and the multiple first driving components are disposed one-to-one with the nucleic acid extraction module (100) and the nucleic acid fragmentation module (200); the motion module and the first driving components can move the nucleic acid extraction module (100) and the nucleic acid fragmentation module (200) in different directions to drive the nucleic acid extraction module (100) and the nucleic acid fragmentation module (200) to dock with the corresponding reaction holes; The library amplification module (300) is mounted on the base plate (1) and provides the amplification reaction temperature required for the corresponding reaction wells; The processor is electrically connected to at least the motion module, the first driving component, the nucleic acid extraction module (100), the nucleic acid fragmentation module (200), and the library amplification module (300).

2. The reaction control system for automated NGS library construction according to claim 1, characterized in that, The nucleic acid extraction module (100) includes: The first lower platform (2) is fixedly connected to the moving end of one of the first drive components; The first upper platform (3) is connected to the side of the first lower platform (2) away from the first drive assembly by multiple bolts, and the distance between the first upper platform (3) and the first lower platform (2) is adjustable; The first elastic element (7) is disposed between the first lower platform (2) and the first upper platform (3), and the two ends of the first elastic element (7) abut against the first lower platform (2) and the first upper platform (3) respectively. The first heating platform (10) is fixedly connected to the side of the first upper platform (3) away from the first lower platform (2). A first temperature sensor (13) is fixedly installed on the first heating platform (10). The first temperature sensor (13) is electrically connected to the processor. The first heating platform (10) is correspondingly set with one of the reaction holes of the reaction device. The first heating element (8) is disposed between the first heating platform (10) and the first upper platform (3). The first heating element (8) is heat-conducting with the first heating platform (10), and the first heating element (8) is insulated from the first upper platform (3). The first heating element (8) is electrically connected to the processor. A high-temperature resistant permanent magnet (37) is obliquely arranged on the side inside the first heating platform (10) and fixed by adhesive or potting.

3. A reaction control system for automated NGS library construction according to claim 1 or 2, characterized in that, The nucleic acid fragmentation module (200) includes: The second lower platform (15) is connected to the moving end of one of the first drive components; The second heating stage (38) is provided corresponding to one of the reaction holes of the reaction device; An ultrasonic component is provided to the reaction orifice corresponding to the second heating stage (38) with the ultrasonic component being electrically connected to the processor. The second elastic element (16) is located between the second lower platform (15) and the ultrasonic component; The fourth elastic element (41) is located between the second heating stage (38) and the ultrasonic component.

4. A reaction control system for automated NGS library construction according to claim 3, characterized in that, The ultrasound assembly includes a first ultrasound fixation component (18), a second ultrasound fixation component (19), and an ultrasound transducer (20); the nucleic acid fragmentation module (200) further includes a second heating element (40) and a first guiding component; The second elastic element (16) is sleeved on one end of the first drive assembly that protrudes from the second lower platform (15); The first ultrasonic fixing member (18) is sleeved on one end of the moving end of the first driving component that protrudes from the second lower platform (15). The two ends of the second elastic member (16) abut against the second lower platform (15) and the first ultrasonic fixing member (18) respectively. The side of the first ultrasonic fixing member (18) away from the second elastic member (16) is provided with a second upper platform (17). The second upper platform (17) is threadedly connected to the moving end of the first driving component. The second ultrasonic fixation member (19) is fixedly attached to the first ultrasonic fixation member (18); The second heating stage (38) is fixedly attached to the first ultrasonic fixation member (18); a second temperature sensor (39) is provided on the second heating stage (38), and the second temperature sensor (39) is electrically connected to the processor; The second heating element (40) is disposed between the first ultrasonic fixation member (18) and the second heating stage (38). The second heating element (40) and the second heating stage (38) are heat-conductingly disposed. The second heating element (40) and the second upper platform (17) are insulated and heat-insulatingly disposed. The second heating element (40) is electrically connected to the processor. The fourth elastic element (41) is disposed between the first ultrasonic fixation element (18) and the second heating stage (38), and the two ends of the fourth elastic element (41) abut against the first ultrasonic fixation element (18) and the second heating stage (38) respectively. The ultrasonic transducer (20) is fixedly installed between the first ultrasonic fixture (18) and the second ultrasonic fixture (19). The top end of the ultrasonic transducer (20) extends through the second ultrasonic fixture (19) / second heating platform (38) / second heating plate (40) and is threadedly connected to an ultrasonic converter (21). The ultrasonic converter (21) is correspondingly set with one of the reaction holes of the reaction device. The ultrasonic transducer (20) is electrically connected to the processor. The first guide assembly includes a first slide rail and a first slider (9) slidably connected to the first slide rail. The first slide rail is fixed to the upper plate (6). The first ultrasonic fixation member (18) is fixed to the first slider (9). The first slider (9) is located between the upper plate (6) and the first ultrasonic fixation member (18).

5. A reaction control system for automated NGS library construction according to claim 3, characterized in that, The first driving component includes: The first push rod linear motor (14) is fixedly connected to the upper plate (6). The moving end of the first push rod linear motor (14) is fixedly connected to the first lower platform (2) / second lower platform (15). The first push rod linear motor (14) is electrically connected to the processor. The second photoelectric sensor (12) is fixed on the lower plate (5). The second photoelectric sensor (12) is correspondingly set to the moving end of the first push rod linear motor (14). The second photoelectric sensor (12) is set at the end of the first push rod linear motor (14) away from the first lower platform (2) / second lower platform (15). The second photoelectric sensor (12) is electrically connected to the processor.

6. A reaction control system for automated NGS library construction according to claim 1, characterized in that, The library expansion module (300) includes: The second drive assembly (310) is fixed relative to the base plate (1) and electrically connected to the processor; The stage assembly is connected to the moving end of the second drive assembly (310). The stage assembly includes a stage, a semiconductor cooling chip (32), and a heat dissipation assembly. The second drive assembly (310) can drive the stage assembly to move so that the stage docks with the corresponding reaction hole. The thermoelectric cooler (32) is electrically connected to the processor. The thermoelectric cooler (32) has a cold end and a hot end, one of which faces the worktable and the other of which faces the heat dissipation assembly.

7. A reaction control system for automated NGS library construction according to claim 6, characterized in that, The workbench includes a third lower table surface (26), a third upper table surface (28), and a third heating table (35). The heat dissipation assembly includes a radiator fixing plate (29) and a radiator (30). The library expansion module (300) also includes a third elastic element (27), a telescopic air duct (42), a ventilation duct (43), a first heat insulation pad (44), a heating cover (34), and a third temperature sensor (36). The third lower platform (26) is fixed to the moving end of the second drive assembly (310); The third upper platform (28) is connected to the third lower platform (26) by multiple bolts, and the distance between the third lower platform (26) and the third upper platform (28) is adjustable; The third elastic member (27) is disposed between the third lower platform (26) and the third upper platform (28), and the two ends of the third elastic member (27) abut against the third lower platform (26) and the third upper platform (28) respectively; The radiator mounting plate (29) is fixed to the third upper platform (28); The heat sink (30) is fixedly connected to the heat sink mounting plate (29), and a fan (31) is fixedly installed on one side of the heat sink (30). The fan (31) is electrically connected to the processor. The two ends of the telescopic air duct (42) are respectively fixed to the radiator fixing plate (29) and the base plate (1); The ventilation duct (43) is fixedly installed on the side of the base plate (1) away from the telescopic duct (42); The first heat insulation pad (44) is disposed between the base plate (1) and the ventilation duct (43); The third heating platform (35) is disposed on the heat sink (30). The third heating platform (35) is disposed corresponding to a reaction hole of the reaction device. A third temperature sensor (36) is disposed on the third heating platform (35). The third heating platform (35) and the third temperature sensor (36) are both electrically connected to the processor. The semiconductor cooling chip (32) is disposed between the heat sink (30) and the third heating stage (35), and the third heating stage (35) and the semiconductor cooling chip (32) are covered with a second heat insulation pad (33). The heating cover (34) is fixedly connected to the radiator (30), and the side of the heating cover (34) facing the radiator (30) abuts against the third heating platform (35).

8. A reaction control system for automated NGS library construction according to claim 7, characterized in that, The second drive component (310) includes: The second push rod linear motor (22) is fixed to the base plate (1) by a motor fixing plate (23), and the second push rod linear motor (22) is electrically connected to the processor; The second guide assembly includes a second slide rail and a second slider (24) slidably connected to the second slide rail. The second slide rail is fixed to the base plate (1), and the second slider (24) is fixed to the third lower platform (26) on the side away from the linear motor (22). The third photoelectric sensor (25) is fixed on the base plate (1). The third photoelectric sensor (25) is correspondingly arranged with the third lower platform (26). The third photoelectric sensor (25) is electrically connected to the processor.

9. A reaction control system for automated NGS library construction according to claim 1, characterized in that, The motion module includes: The lead screw assembly includes a lead screw (4), a lead screw fixing structure, and a power motor. The lead screw (4) is rotatably connected to the lead screw fixing structure. One end of the lead screw (4) is coaxially fixed to the power motor. The power motor is fixed to the lead screw fixing structure. The lead screw fixing structure is fixed to the base plate (1). The power motor is electrically connected to the processor. The lower plate (5) is threadedly connected to the lead screw (4), the lower plate (5) is slidably connected to the bottom plate (1), and the lower plate (5) is fixedly connected to the upper plate (6); The first photoelectric sensor (11) is fixed on the base plate (1) and is correspondingly arranged with the lower plate (5). The first photoelectric sensor (11) is electrically connected to the processor.

10. A reaction control system for automated NGS library construction according to claim 2, characterized in that, The first heating element (8) includes: plate body; Multiple resistors (802) are fixed to the plate, and the multiple resistors (802) are distributed in an array; A terminal block (801) is fixed to the board and electrically connected to all of the resistors (802). The terminal block (801) is also electrically connected to the processor. A thermal fuse (803) is connected in series between any two adjacent resistors (802).

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