Nucleic acid sequencing pretreatment workstation and sequencing pretreatment method

Abstract

The invention provides a nucleic acid sequencing pretreatment workstation and a sequencing pretreatment method, the nucleic acid sequencing pretreatment workstation comprises: a nucleic acid extraction system configured to controllably extract nucleic acid molecules from a biological sample; the library construction system is configured to controllably prepare the nucleic acid molecules into a library capable of being used for on-machine sequencing; the quality control system is configured to controllably detect the concentration of the nucleic acid extraction product and add a homogenization reagent into the nucleic acid extraction product according to a detection result and library construction sample loading parameters; and / or, controllably performing concentration detection on the library construction product, adding a homogenization reagent into the library construction product according to a detection result, and diluting the library construction product to the concentration required by nucleic acid sequencing. According to the technical scheme, through the cooperation of the nucleic acid extraction system, the quality control system and the library construction system, the operations of nucleic acid extraction, nucleic acid extraction product substance control, library construction, library file product substance control and the like are realized, the automation degree of nucleic acid sequencing pretreatment is improved, and the consistency of nucleic acid sequencing is improved.

Description

[0001] This application claims the priority of the Chinese patent application filed with the China Patent Office on September 14, 2024, with application number 202411299715.1 and application name “Library construction workstation and nucleic acid library construction method”, all contents of which are incorporated by reference in this application. Technical Field

[0002] The present application relates to the technical field of nucleic acid sequencing, and in particular to a nucleic acid sequencing pre-processing workstation and a sequencing pre-processing method. Background Art

[0003] Nucleic acid sequencing technology is the most commonly used technology in modern molecular biology research, but a complex processing process is required from sample extraction to sequencing, including nucleic acid extraction, nucleic acid extraction product quality control, library construction, library construction product quality control, etc. There are two traditional methods for this process: one is manual operation by experimenters, which has the disadvantages of high labor intensity, easy contamination, and poor consistency; the second method uses a traditional nucleic acid extractor plus a single-function library construction workstation. This method is semi-automatic, and the quality control of the intermediate nucleic acid extraction product and the quality control and homogenization of the library construction product all require manual operation by experimenters, which has a poor user experience. Summary of the invention

[0004] The present application provides a nucleic acid sequencing pre-processing workstation to improve the automation effect and quality control effect of nucleic acid sequencing pre-processing.

[0005] In a first aspect, a nucleic acid sequencing pre-processing workstation is provided, the nucleic acid sequencing pre-processing workstation comprising:

[0006] A nucleic acid extraction system configured to controllably extract nucleic acid molecules from a biological sample;

[0007] A library construction system configured to controllably prepare the nucleic acid molecules into a library that can be used for sequencing;

[0008] The quality control system is configured to controllably detect the concentration of the nucleic acid extraction product and add a homogenizing agent to the nucleic acid extraction product according to the detection result and the library construction loading parameter; and / or controllably detect the concentration of the library construction product and add a homogenizing agent to the library construction product according to the detection result and dilute it to the concentration required for nucleic acid sequencing. In the above technical scheme, through the cooperation of the nucleic acid extraction system, the quality control system and the library construction system, operations such as nucleic acid extraction, nucleic acid extraction product quality control, library construction, and library construction product quality control are realized, which improves the automation of nucleic acid sequencing pre-processing and improves the consistency of nucleic acid sequencing.

[0009] In one possible implementation, the quality control system includes a quantitative analyzer, a quality control operator assembly, a transmission mechanism, a quality control pipetting assembly, a reaction container, a quality control container, and a detection reagent container;

[0010] The quality control container is configured to accommodate the nucleic acid extraction product or library construction product to be detected, and can be placed in the quantitative analyzer to realize detection;

[0011] The detection reagent container is configured to accommodate one or more detection reagents required for the quantitative analyzer to perform concentration detection and reagents for adjusting the concentration of nucleic acid extraction products and / or library construction products;

[0012] The conveying mechanism is configured to reciprocate the quality control container between the working area of ​​the quality control operating hand assembly and the working area of ​​the quality control pipetting assembly;

[0013] The quality control operator assembly is configured to take out the quality control container from the storage area of ​​the quality control container and place it on the conveying mechanism, take out the quality control container from the conveying mechanism and place it into the quantitative analyzer, take out the quality control container from the storage area of ​​the quality control container and place it into the quantitative analyzer, take out the quality control container that has completed the test from the quantitative analyzer and place it back into the storage area of ​​the quality control container;

[0014] The quality control pipetting component is configured to draw a certain amount of detection reagent from the detection reagent container and add it to the quality control container, and to draw a certain amount of reagent for adjusting the concentration of nucleic acid extraction products and / or library construction products and add it to the construction reaction container;

[0015] The construction reaction container is configured to accommodate the nucleic acid extraction product after quality control and provide a reaction space for the library construction process.

[0016] In one possible implementation, the conveying mechanism includes a conveyor belt and at least two accommodating positions fixed on the conveyor belt for accommodating the quality control container; wherein,

[0017] The conveyor belt is configured to reciprocate the quality control container between the working area of ​​the quality control operating hand assembly and the working area of ​​the quality control pipetting assembly.

[0018] In one possible implementation, the library construction system includes a PCR instrument, a library construction operator component, a library construction pipetting component, a library construction reagent container, an oscillating heating component, and a magnet component;

[0019] The library construction operator component is configured to take out the construction reaction container containing the nucleic acid extraction product after quality control from the quality control system, place the construction reaction container in the reagent adding area of ​​the library construction system, and send the construction reaction container loaded with reagents to the PCR instrument; and / or send the construction reaction container containing the library construction product to the quality control system for quality control;

[0020] The library construction reagent container is configured to contain one or more library construction reagents required for library construction;

[0021] The magnet assembly is configured to provide a necessary magnetic field environment for magnetic bead purification;

[0022] The oscillating heating component is configured to provide a reaction space and reaction temperature for magnetic bead purification during library construction;

[0023] The library construction pipetting component is configured to add library construction reagents from the library construction reagent container to the construction reaction container.

[0024] In one implementation, the invention further comprises a waste container for carrying discarded pipetting heads of the library construction pipetting assembly.

[0025] In one possible implementation, it further includes a frame, on which a workbench is disposed, and the nucleic acid extraction system, the quality control system, and the library construction system are all disposed on the workbench.

[0026] In one achievable manner, when the library construction system includes a library construction manipulator component and a library construction pipetting component, the library construction manipulator component and the library construction pipetting component are arranged on the same three-axis motion platform, and the three-axis motion platform is arranged on the frame.

[0027] In one possible implementation, it further includes an information acquisition module disposed on the three-axis motion platform, and the information acquisition module is used to acquire information about consumables in the nucleic acid sequencing pre-processing workstation.

[0028] In one possible implementation, an air filter device is further included, and the air filter device is arranged on the top of the frame.

[0029] In a second aspect, a method for pre-processing nucleic acid sequencing is provided, the method comprising:

[0030] The nucleic acid extraction system can controllably extract nucleic acid molecules from biological samples;

[0031] The quality control system can controllably detect the concentration of the nucleic acid extraction product and add a homogenizing agent to the nucleic acid extraction product according to the detection result and the library construction loading parameter; the library construction system can controllably prepare the nucleic acid molecules into a library for sequencing.

[0032] In the above technical scheme, through the cooperation of the nucleic acid extraction system, the quality control system, and the library construction system, operations such as nucleic acid extraction, quality control of nucleic acid extraction products, library construction, and quality control of construction products are realized, which improves the degree of automation of nucleic acid sequencing pre-processing and improves the consistency and stability of nucleic acid sequencing.

[0033] In one achievable embodiment, the method further comprises: a quality control system controllably detects the concentration of the library construction product, and according to the detection result, a homogenization reagent is added to the library construction product and diluted to the concentration required for nucleic acid sequencing. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 A structural block diagram of a nucleic acid sequencing pre-processing workstation provided in an embodiment of the present application;

[0035] Figure 2 A structural block diagram of the library construction system provided in the embodiment of the present application;

[0036] Figure 3 A structural block diagram of the quality control system provided in the embodiment of the present application;

[0037] Figure 4 A schematic diagram of the structure of a nucleic acid sequencing pre-processing workstation provided in an embodiment of the present application;

[0038] Figure 5 A schematic diagram of the arrangement of the modules of the library construction workstation provided in the embodiment of the present application;

[0039] Figure 6 A schematic diagram of the quality inspection module layout provided in an embodiment of the present application;

[0040] Figure 7 A side view of a library construction workstation provided in an embodiment of the present application;

[0041] Figure 8 A side view from another angle of the library construction workstation provided in an embodiment of the present application. DETAILED DESCRIPTION

[0042] In order to make the objectives, technical solutions and advantages of the present application clearer, the present application will be further described in detail below in conjunction with the accompanying drawings.

[0043] It should be noted that, unless otherwise defined, the technical terms or scientific terms used in one or more embodiments of this specification should be understood by people with ordinary skills in the field to which this disclosure belongs. The "first", "second" and similar words used in one or more embodiments of this specification do not indicate any order, quantity or importance, but are only used to distinguish different components. "Include" or "comprise" and similar words mean that the elements or objects appearing before the word cover the elements or objects listed after the word and their equivalents, without excluding other elements or objects. "Connect" or "connected" and similar words are not limited to physical or mechanical connections, but may include electrical connections, whether direct or indirect. "Up", "down", "left", "right" and the like are only used to indicate relative positional relationships. When the absolute position of the described object changes, the relative positional relationship may also change accordingly.

[0044] For the convenience of understanding the nucleic acid sequencing pre-treatment workstation provided in the embodiment of the present application, its application scenario is first described. The nucleic acid sequencing pre-treatment workstation provided in the embodiment of the present application can be used in conjunction with a nucleic acid sequencer to prepare and provide a library required for sequencing on the nucleic acid sequencer. In the current pre-treatment method, the process required from nucleic acid extraction to library construction is relatively complicated, mainly through manual operation by experimenters, resulting in poor consistency and stability of pre-treatment results. For this reason, the embodiment of the present application provides a nucleic acid sequencing pre-treatment workstation to improve the automation of pre-treatment. It is described in detail below in conjunction with specific drawings and embodiments.

[0045] refer to Figure 1 As shown, Figure 1The structural block diagram of the nucleic acid sequencing pre-processing workstation provided in the embodiment of the present application is shown. The nucleic acid sequencing pre-processing workstation provided in the embodiment of the present application mainly includes a nucleic acid extraction system 100, a library construction system 200 and a quality control system 300. Among them, the nucleic acid extraction system 100 is configured to controllably extract nucleic acid molecules (such as DNA or RNA) from biological samples. And the library construction system 200 is configured to controllably prepare nucleic acid molecules (such as DNA or RNA) into libraries that can be used for sequencing on a machine. In addition, the quality control system 300 is used to perform quality control on nucleic acid molecules. Specifically, the quality control system 300 is configured to controllably detect the concentration of the nucleic acid extraction product, and add a homogenizing agent to the nucleic acid extraction product according to the test results and the library construction loading parameters; and / or, controllably detect the concentration of the library construction product, and add a homogenizing agent to the library construction product according to the test results and dilute it to the concentration required for nucleic acid sequencing. That is, the quality control system 300 provided in the implementation of the present application can only perform quality control on the nucleic acid molecules extracted by the nucleic acid extraction system 100, or only perform quality control on the library constructed by the library construction system 200, or simultaneously perform quality control on the nucleic acid molecules extracted by the nucleic acid extraction system 100 and the library constructed by the library construction system 200.

[0046] Continue to refer Figure 1 The nucleic acid sequencing pre-processing workstation provided in the embodiment of the present application also includes an electronic control system 400 and a host computer 500, wherein the electronic control system 400 is configured to control the operation and work of the nucleic acid extraction system 100, the library construction system 200, and the quality control system 300 according to the instructions of the host computer 500; and the host computer 500 is configured to control the operation and work of the nucleic acid extraction system 100, the library construction system 200, and the quality control system 300 by sending control instructions to the electronic control system 400. The operation and work of the nucleic acid extraction system 100, the library construction system 200, and the quality control system 300 refer to the necessary actions required for the nucleic acid extraction system 100, the library construction system 200, and the quality control system 300 to complete their corresponding functions. The control of the nucleic acid extraction system 100, the library construction system 200, and the quality control system 300 is realized through the electronic control system 400 and the host computer 500, so that the entire nucleic acid sequencing pre-processing workstation can be automatically operated.

[0047] It can be seen from the above description that the nucleic acid sequencing pre-processing workstation provided in the embodiment of the present application realizes operations such as nucleic acid extraction, quality control of nucleic acid extraction product, library construction, and quality control of library construction product through the cooperation of the nucleic acid extraction system, the quality control system, and the library construction system, thereby improving the degree of automation of the nucleic acid sequencing pre-processing process and improving the consistency and stability of the pre-processing results.

[0048] The specific structure and operation of each module in the nucleic acid sequencing pre-processing workstation provided in the embodiments of the present application are described in detail below in conjunction with specific drawings and embodiments.

[0049] To facilitate understanding, we first introduce several major processing processes and technical principles involved in nucleic acid sequencing pre-processing.

[0050] Nucleic acid extraction is a technique that separates nucleic acids from biological samples by physical, chemical, biological methods or a combination of these methods. It is mainly used to separate nucleic acid molecules (such as DNA or RNA) from biological samples for subsequent experimental analysis, such as sequencing analysis.

[0051] Taking chemical separation as an example, by lysing sample cells with cell lysis solution, nucleic acid molecules can be released from sample cells, and nucleic acid molecules exist in the lysate solution together with impurities such as proteins. If pure nucleic acid molecules are to be obtained, the lysate needs to be further purified. Taking magnetic bead purification as an example, magnetic beads are added to the lysate, and nucleic acid molecules released from sample cells are specifically adsorbed on the surface of magnetic beads, while impurities such as proteins are not adsorbed and remain in the lysate. After a certain reaction time, the magnetic beads adsorbed with nucleic acid molecules are separated from the solution under the action of a magnetic field, and 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, in order to wash cleanly, washing can be repeated many times to recover pure magnetic beads adsorbed with nucleic acid molecules. Finally, the nucleic acid molecules and magnetic beads are desorbed by elution with an elution solution. After a certain reaction time, the magnetic beads are separated from the nucleic acid molecules again under the action of a magnetic field. After removing the magnetic beads, only pure nucleic acid molecules remain in the nucleic acid extraction product.

[0052] In one achievable manner, taking chemical separation and magnetic bead purification as examples, the nucleic acid extraction system 100 includes at least a nucleic acid extraction platform and a magnetic rod / magnetic rod sleeve assembly. Among them, the nucleic acid extraction platform is provided with an extraction operation container (e.g., a single reagent strip or a deep well plate) and a heating device (e.g., a heating block). In addition to accommodating one or more reagents required for nucleic acid extraction (e.g., cell lysis solution, washing solution, elution solution), the extraction operation container can also accommodate biological samples and magnetic particles (e.g., magnetic beads), and provide reaction space for various chemical reactions (e.g., cleavage reaction, washing reaction, elution reaction) during nucleic acid extraction; 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 set on the magnetic rod to prevent the magnetic rod from directly contacting the nucleic acid extraction reagent and corroding the magnetic rod. When the magnetic rod / magnetic rod sleeve assembly enters the extraction operation container through the motion mechanism, it can provide the necessary magnetic field environment for the washing reaction and elution reaction during nucleic acid extraction.

[0053] It should be noted here that the nucleic acid extraction system 100 can perform nucleic acid extraction processing on multiple biological samples in batches.

[0054] When the quality control system 300 performs quality control on the nucleic acid molecules extracted by the nucleic acid extraction system 100, the nucleic acid extraction product can be drawn from the extraction operation container, and the nucleic acid extraction product contains nucleic acid molecules.

[0055] In the next generation sequencing (NGS) technology, nucleic acid molecules (such as DNA or RNA) extracted from biological samples need to be broken by physical or enzymatic methods, for example, by ultrasound, to form nucleic acid fragments. The two ends of the nucleic acid fragments are first filled with enzymes, and then the two ends of the fragments are connected to a specific DNA sequence (usually, this specific DNA sequence is also called a linker) with a specific enzyme. Finally, the nucleic acid fragments formed are called libraries in the industry.

[0056] In order to save sequencing costs, generally, multiple biological samples will be sequenced in a sequencer at the same time. In order to distinguish the sequencing results of different samples, when preparing libraries of different samples, a DNA sequence (usually containing 6-8 bases) that can identify the source of the sample will be included in the connector. 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 library connector contains its own sample tag.

[0057] like Figure 2 As shown, the library construction system 200 provided in the embodiment of the present application at least includes a PCR (Polymerase chain reaction) instrument 210, a library construction operator component 220 ( Figure 2 Only the working area is shown), library construction pipetting component 230 ( Figure 2 Only the working area is shown), library construction reagent container 240, oscillating heating component 250 and magnet component 260. It should be noted that Figure 2 It is merely illustrative and should not be construed as limiting the positions of the various parts.

[0058] Among them, the library construction reagent container 240 (such as a test kit) can accommodate one or more reagents required for library construction, and the library construction reagent container 240, the oscillation heating component 250 and the magnet component 260 are respectively located in their respective storage areas, and their respective storage areas are located within the working area range of the library construction operator component 220 and the library construction pipetting component 230. The storage area of ​​the library construction reagent container 240 generally needs to be in a low-temperature refrigeration environment to facilitate the low-temperature refrigeration of the library construction reagent. The oscillation heating component 250 is configured to provide a reaction space and reaction temperature for the magnetic bead purification during the library construction process. Among them, the oscillation heating component 250 is provided with a purification container (such as a deep well plate) and an oscillation heating device, the purification container can provide a reaction space for the magnetic bead purification during the library construction process, the oscillation heating device can provide a suitable reaction temperature and reaction conditions for the magnetic bead purification, and at the same time, the magnet component 260 can provide the necessary magnetic field environment for the magnetic bead purification. The PCR instrument 210 is used to perform an amplification reaction on the nucleic acid molecules in the (quality-controlled) nucleic acid extraction product contained in the reaction container 350 .

[0059] After the nucleic acid extraction quality control is completed, the library construction operator component 220 is responsible for taking out the construction reaction container 350 (with the nucleic acid extraction product added) from the quality control system 300 and placing it in a specific storage area in the library construction system 200. In this storage area, various reaction reagents are added to the construction reaction container 350. For the convenience of description, this storage area can be called a reagent adding area. Since the construction reaction container stores nucleic acid molecules, the reagent adding area generally needs to be in a low-temperature refrigeration environment to facilitate the low-temperature refrigeration of nucleic acid molecules.

[0060] Since the entire library construction process includes multiple reaction steps, for each reaction step, the library construction pipetting component 230 is first responsible for aspirating the corresponding reaction reagent from the library construction reagent container 240 and adding it to the construction reaction container 350 (to which the nucleic acid extraction product after quality control has been added), and the library construction operator component 220 is then responsible for placing the construction reaction container 350 (to which the nucleic acid extraction product and the corresponding reaction reagent have been added in sequence) into the PCR instrument 210 for reaction. After the reaction is completed, the library construction operator component 220 takes the construction reaction container 350 out of the PCR instrument 210 and puts it back to the reagent adding area to wait for the addition of the reaction reagent for the next reaction, and repeats the above process.

[0061] In the process of library construction, after connecting the connectors at both ends of the nucleic acid fragments, the connection products need to be purified, and a pure library can be obtained after purification. In addition, since the amount of library obtained at this time is small, library amplification is usually required, and after library amplification, the amplified products also need to be purified to obtain a pure library. If magnetic bead purification is adopted, the library construction reagent container 240 can accommodate one or more reagents required for library construction (including washing solution and eluent required for magnetic bead purification), as well as magnetic beads or other magnetic particles. During the magnetic bead purification reaction of the connection product or amplification product, the library construction pipetting component 230 is responsible for first sucking the connection product / amplification product from the construction reaction container 350 and adding it to the purification container of the oscillating heating component 250, and then sucking the magnetic beads from the library construction reagent container 240 and adding them to the purification container (with the connection product / amplification product added). After a certain reaction time, the library construction operator component 220 is responsible for transferring the purification container (the library has been adsorbed on the surface of the magnetic beads) to the magnet component 260. Under the action of the magnetic field, the magnetic beads adsorbed with the library are separated from the solution, and the library construction pipetting component 230 then sucks out the supernatant in the purification container, leaving the magnetic beads adsorbed with the library. The library construction pipetting component 230 continues to suck the washing solution from the library construction reagent container 240 and add it to the purification container. After a certain reaction time, the supernatant is sucked away. According to experimental needs, the library construction pipetting component 230 can be repeatedly operated for multiple washings. After washing, the library construction operation hand component 220 transfers the purification container to the oscillating heating component 250, and the library construction pipetting component 230 continues to absorb the eluate from the library construction reagent container 240 and add it to the purification container. After a certain reaction time, the library and the magnetic beads are desorbed, and the library construction pipetting component 230 then absorbs the supernatant (i.e., the library construction product) in the purification container and adds it to the construction reaction container 350.

[0062] Generally, a sealing film is attached to the upper surface of the library construction reagent container 240 to facilitate the storage and transportation of the internal reagents. After the reagent container is loaded into the sequencing pre-processing instrument, it needs to be pierced by the piercing component 270 ( Figure 2 After the sealing film is pierced (only the working area is shown), the corresponding pipetting component can draw reagents from the library file reagent container 240, and the storage area of ​​the library construction reagent container 240 is located within the working area of ​​the piercing component 270.

[0063] In addition, considering that the capacity of magnetic beads, washing solution, and eluent required in the magnetic bead purification process is large and does not need to be in a low-temperature refrigeration environment, in addition to the library construction reagent container 240, the library construction system 200 can further be provided with a large-capacity reagent container 290 for storing large-capacity reagents such as magnetic beads, washing solution, and eluent.

[0064] It should be noted that the library construction operator component 220 and the library construction pipetting component 230 can be independently set. Considering that the library construction operator component 220 and the library construction pipetting component 230 do not need to work in parallel, the two can also be integrated into one to save space. In addition, the library construction system 300 can perform library construction processing on nucleic acid extraction products of multiple biological samples in batches.

[0065] In one possible implementation, the library pipetting component 220 can be a pipetting pump. To cooperate with the operation of the pipetting pump, the pipetting pump needs to be equipped with a pipetting gun tip. When the pipetting work starts, the pipetting pump sets the pipetting head cover on its end. After the pipetting work is completed, the pipetting pump detaches the pipetting head from its end. Correspondingly, the library construction system 200 is also provided with a pipetting head storage area, and a waste container 280 for carrying or accommodating discarded pipetting heads of the library construction pipetting component. Used pipetting heads (discarded pipetting heads) will be put into the waste container 280. Figure 2 As shown, the waste container is arranged at a corner of the pre-processing workstation.

[0066] In one possible implementation, the library construction operator component and the library construction pipetting component are arranged on a three-axis motion platform, so that the library construction operator component and the library construction pipetting component are driven synchronously through the same three-axis motion platform through the three-axis motion platform. In order to facilitate the description of the movement direction of the three-axis motion platform, an XYZ coordinate system is constructed, in which the X direction is perpendicular to the Y direction and the Z direction, and the X direction and the Y direction are parallel to the placement plane of the nucleic acid extraction system, the library construction system and the quality control system. The three-axis motion platform can move along the above-mentioned X direction, Y direction and Z direction respectively to meet the movement requirements of the library construction operator component and the library construction pipetting component.

[0067] In an achievable scheme, the nucleic acid sequencing pre-processing workstation provided in the embodiment of the present application further includes an information acquisition module (e.g., an industrial camera), which is used to be arranged on the three-axis motion platform, and the information acquisition module is used to collect information about consumables in the nucleic acid sequencing pre-processing workstation. Among them, the consumables include but are not limited to extraction operation containers, library construction reagent containers, etc. Thus, the information can be transmitted to the host computer 500 for recording. For example, a QR code is provided on the consumable, and the QR code carries the consumable information. The QR code on the consumable is photographed by controlling the industrial camera so that the host computer 500 can identify the consumable information according to the QR code.

[0068] The concentration detection (or concentration quantitative analysis) of nucleic acid molecules (such as DNA or RNA) in nucleic acid extraction products is very important. Usually, the subsequent library construction process has certain requirements for the total amount of nucleic acid molecules required. Once the actual nucleic acid molecule input exceeds the total amount of nucleic acid molecules required for the subsequent library construction process, it will affect the amplification efficiency during library construction. Therefore, before library construction, it is also necessary to detect the concentration of nucleic acid molecules in the nucleic acid extraction product. After detecting the concentration of nucleic acid molecules, the total capacity of the required nucleic acid extraction product can be further determined according to the concentration of nucleic acid molecules and the total amount of nucleic acid molecules required for the subsequent library construction process. In addition, when the detected nucleic acid molecule concentration is too high, the total capacity of the required nucleic acid extraction product will be lower than the minimum pipetting volume of the pipetting device and affect the pipetting accuracy. Therefore, it is necessary to add a certain amount of diluent / reagent (e.g., pure water) to the nucleic acid extraction product before pipetting for appropriate dilution. Several common concentration detection methods include, for example, spectrophotometry, fluorescent dye detection, microfluidics analysis, or capillary gel electrophoresis.

[0069] In addition, the quality of the constructed library is crucial for the data quality of the subsequent gene sequencing output. Therefore, it is also necessary to detect and control the quality of the library in the library construction product before sequencing on the machine. Usually, the library quality detection includes at least one of the library length detection, library concentration detection and library pollutant detection. Among them, the library concentration can be detected by library concentration detection (or concentration quantitative analysis), and when the detected library concentration is too high, the total capacity of the library construction product required for subsequent sequencing will be lower than the minimum pipetting volume of the pipetting device and affect the pipetting accuracy. Therefore, it is necessary to add diluent / reagent (e.g., pure water) to the library construction product before pipetting for moderate dilution. In addition, due to the difference between the library concentrations of multiple biological samples and the difference between the sequencing data output, the total capacity of the library construction products of multiple biological samples required for subsequent sequencing is different and ultimately affects the balance of the sequencing data output of multiple biological samples. Therefore, it is also necessary to add a certain amount of diluent / reagent (e.g., pure water) to dilute the library construction products of some biological samples before pipetting to narrow the gap between the total capacity of the library construction products of multiple biological samples. Several common concentration detection methods include, for example, spectrophotometry, fluorescent dye detection, microfluidics analysis, or capillary gel electrophoresis.

[0070] Here, it should be noted that for the quality control of library construction products and nucleic acid extraction products, their concentration detection can adopt the same method or different methods, and this application does not limit this.

[0071] In the embodiment of the present application, at least one of the library construction product and the nucleic acid extraction product is quality controlled by the quality control system 300. The specific structure of the quality control system 300 is described in detail below with reference to the accompanying drawings.

[0072] refer to Figure 3 As shown, Figure 3 The quality control system 300 provided in the embodiment of the present application at least comprises a quantitative analyzer 310, a quality control operator assembly 320 ( Figure 3 Only the working area is shown), the transmission mechanism 330, the quality control pipetting component 340 ( Figure 3 Only the working area is shown), a reaction container 350, a quality control container 360 and a detection reagent container 370 are constructed. It should be noted that Figure 3 It is merely illustrative and should not be construed as limiting the positions of the various parts.

[0073] Among them, the quality control container 360 (such as a centrifuge tube) can contain the test object and can be placed in the quantitative analyzer 310 to realize concentration detection; the detection reagent container 370 (such as a reagent kit) can contain one or more detection reagents required for the quantitative analyzer 310 to perform concentration detection and reagents for adjusting the concentration of nucleic acid extraction products and library construction products. The construction reaction container 350, the quality control container 360, and the detection reagent container 370 are respectively located in their respective storage areas, the quality control operation hand assembly 320 and the quality control pipetting assembly 340 work in their respective working areas, the storage area of ​​the quality control container 360 is within the working area of ​​the quality control operation hand assembly 320, and the storage areas of the construction reaction container 350 and the quality control reagent container 370 are within the working area of ​​the quality control pipetting assembly 340. A transport mechanism 330 is provided between the working area of ​​the quality control operating hand assembly 320 and the working area of ​​the quality control pipetting assembly 340 . The transport mechanism 330 can transport the quality control container 360 back and forth between the working area of ​​the quality control operating hand assembly 320 and the working area of ​​the quality control pipetting assembly 340 .

[0074] Before quality control begins, the quality control operator component 320 is responsible for taking out the quality control container 360 from the storage area of ​​the quality control container 360 and placing it on the conveying mechanism 330. The conveying mechanism 330 conveys the quality control container 360 to the working area of ​​the quality control pipetting component 340. The quality control pipetting component 340 is responsible for aspirating a certain amount of detection reagent from the detection reagent container 370 and adding it to the quality control container 360. The conveying mechanism 330 then conveys the quality control container 360 (with the detection reagent added) back to the working area of ​​the quality control operator component 320. The quality control operator component 320 is then responsible for placing the quality control container 360 (with the detection reagent added) back to the storage area of ​​the quality control container 360.

[0075] After the quality control starts, the quality control operator component 320 is responsible for taking out the quality control container 360 (with the detection reagent added) from the storage area of ​​the quality control container 360 and placing it on the conveying mechanism 330. The conveying mechanism 330 conveys the quality control container 360 (with the detection reagent added) to the working area of ​​the quality control pipetting component 340. The quality control pipetting component 340 is responsible for aspirating a certain amount of nucleic acid extraction product / library construction product from the construction reaction container 350 and adding it to the quality control container 360, and stirring it evenly. The conveying mechanism 330 then conveys the quality control container 360 (with the detection reagent and nucleic acid extraction product / library construction product added in turn) back to the working area of ​​the quality control operator component 320. The quality control operator component 320 is then responsible for placing the quality control container 360 (with the detection reagent and nucleic acid extraction product / library construction product added in turn) back to the storage area of ​​the quality control container 360.

[0076] After the detection reagent and nucleic acid extraction product / library construction product in the quality control container 360 react for a period of time, the quality control operator component 320 is responsible for taking out the quality control container 360 from the storage area of ​​the quality control container 360 and placing it in the quantitative analyzer 310 for concentration detection. After the detection is completed, the quality control operator component 320 is responsible for taking out the quality control container 360 and returning it to the storage area. If the concentration of the detected nucleic acid molecules is higher than the required concentration, according to the test results, the quality control pipetting component 340 is also responsible for drawing a certain amount of nucleic acid extraction product from the extraction operation container and adding it to the construction reaction container 370, and drawing a certain amount of pure water from the detection reagent container 370 and adding it to the construction reaction container 370 for dilution. Among them, the construction reaction container 350 (such as a microplate) can accommodate the nucleic acid extraction product after quality control, and further provide a reaction space for some chemical reactions in the library construction process.

[0077] Similarly, if the detected library concentration is higher than the required concentration, based on the test results, the quality control pipetting component 340 is also responsible for drawing a certain amount of pure water from the test reagent container 370 and adding it to the construction reaction container 370 for dilution.

[0078] It should be noted here that the quality control system 300 can perform quality control processing on the nucleic acid extraction products / library construction products of multiple biological samples in batches. In the batch processing scenario, the quality control operator component 320 can take and place the quality control containers 360 one by one, or can take and place multiple quality control containers 360 in batches at one time; correspondingly, the conveying mechanism 330 can convey the quality control containers 360 one by one, or can convey multiple quality control containers 360 in batches at one time; the quality control pipetting component 340 can be a single-channel pipetting component, which draws the detection reagents one by one and adds them to the quality control container 360 one by one, or can be a multi-channel pipetting component, which draws the detection reagents in batches at one time and adds them to multiple quality control containers 360 in batches at one time. It can be freely set according to the occupied space and work efficiency. Figure 3 This is just an example. In this example, the quality control operator assembly 320 takes and places the quality control containers 360 one by one. The conveying mechanism 330 is provided with two container positions, and can reciprocate one quality control container 360 in opposite directions. The quality control pipetting assembly 340 is a single-channel pipetting assembly.

[0079] In one possible implementation, the quality control pipetting component 340 can be a pipetting pump. To cooperate with the work of the pipetting pump, the pipetting pump needs to be equipped with a pipetting head for pipetting. When the pipetting work starts, the pipetting pump sets the pipetting head cover on its end. After the pipetting work is completed, the pipetting pump detaches the pipetting head from its end. Correspondingly, the quality control system 300 is also provided with a pipetting head storage area, such as Figure 3 shown.

[0080] In one practicable manner, the conveying mechanism 330 includes a conveyor belt and at least two receiving positions fixed on the conveyor belt for receiving the quality control container; wherein the conveyor belt is configured to reciprocate the quality control container between the receiving positions in the working area of ​​the quality control operator assembly and the working area of ​​the quality control pipetting assembly. It should be understood that the arrangement area of ​​the conveying mechanism 330 is not limited to the specific structure of the above example, and it can realize the reciprocating movement of the quality control container 360 to various positions to which it is required to move.

[0081] In one achievable manner, the quality control manipulator assembly 320 may be a rotating jaw, which can grasp the quality control container 360 and open or close the quality control container 360. In addition, the rotating jaw is arranged on a three-axis motion platform, so that the rotating jaw can be driven to move within a certain range through the three-axis motion platform to realize the necessary functions of the manipulator. The quality control pipetting assembly 340 can also be carried on another three-axis motion platform, so that the quality control pipetting assembly 340 can be driven to move at different positions through the three-axis motion platform to meet the needs of work. The moving direction of the three-axis motion platform can refer to the X direction, Y direction and Z direction shown in the above example.

[0082] When the quality control system 300 performs quality control on multiple quality control containers 360, the quality control operating hand assembly 320 and the quality control liquid transfer assembly 340 cooperate with the conveying mechanism 330 to open the lids, transfer, add liquid, etc. of the multiple quality control containers 360. And for any quality control container 360, the quality control operating hand assembly 320, the quality control liquid transfer assembly 340 and the conveying mechanism 330 disclosed in the embodiment of the present application are not sent to the quantitative analyzer 310 after adding the quality control reagent, adding the nucleic acid molecule, blowing and mixing, and letting it stand, and then operating another quality control container 360, but use the time interval of the quality control container 360 when transferring, adding liquid or standing to operate another quality control container 360, so as to improve the efficiency of the whole process.

[0083] Exemplarily, during the quality control operation of nucleic acid molecules, the quality control operator hand assembly 320 transfers the No. 1 quality control container 360 from the storage area to the receiving position of the conveyor belt, rotates to open the cover, and the quality control operator hand assembly 320 puts the tube cover back into the No. 1 hole in the storage area. At the same time, the conveying mechanism 330 moves the No. 1 quality control container 360 to the working position of the quality control pipetting assembly 340 (the position of the detection reagent container 370), and at the same time, the quality control pipetting assembly 340 loads a pipetting head in the pipetting head box, draws the quality control reagent from the detection reagent container 370 and adds it to the quality control container 360; then the quality control operator hand assembly 320 puts the No. 1 quality control container 360 back to the storage area. In this way, the operation of adding quality control reagents to multiple quality control containers 360 is completed. In this process, the nucleic acid extraction system 100 completes the extraction of nucleic acids to generate nucleic acid molecules, and the nucleic acid molecules are located in the extraction kit. Afterwards, the quality control system 300 places the quality control container No. 1 360 containing the quality control reagent into the receiving position of the conveying mechanism 330, and the quality control pipetting component 340 absorbs the nucleic acid molecules from the elution well of the pipette tip extraction kit loaded in the pipette tip box, and transfers them to the quality control container No. 1 360 in the corresponding receiving position of the conveyor belt, and mixes them by blowing. At the same time, the quality control operation hand component 320 grabs the quality control container No. 2 360 from the storage area, transfers it to another receiving position of the conveyor belt, and rotates to open the cover. At the same time, the conveying mechanism 330 transfers the No. 1 quality control container 360 to the operating position of the quality control operator assembly 320, and the quality control operator assembly 320 screws the tube cover of the No. 2 quality control container 360 onto the No. 1 quality control container 360, and transfers the No. 1 quality control container 360 to the No. 2 hole in the storage area. After a certain interval, the quality control operator assembly 320 grabs the No. 3 quality control container 360 from the storage area and places it in the receiving position of the conveyor belt. During the time of closing the cover and grabbing a new tube, the quality control pipetting assembly 340 loads the sample into the No. 2 quality control container 360 and mixes it by blowing, and this cycle repeats. After the quality control container No. 1 360 is incubated for an appropriate period of time, the hatch of the quantitative analyzer 310 is controlled to open. During the interval, the quality control operator component 320 grabs the quality control container No. 1 360 and puts it into the quantitative analyzer 310, and controls the hatch of the quantitative analyzer 310 to close. The host computer 500 issues a detection instruction. After the detection, the quantitative analyzer 310 transmits the data to the host computer 500 for storage and processing. At the same time, the hatch of the quantitative analyzer 310 is controlled to open, and the quality control operator component 320 takes the quality control container No. 1 360 out of the quantitative analyzer 310 and puts it back to the corresponding position in the storage area, and the cycle continues.

[0084] In the above scheme, the operations on multiple quality control containers 360 are performed by utilizing the transfer, liquid addition, and static intervals of each quality control container 360, so that the quality control system 300 can reasonably utilize the time difference to increase the operating efficiency of the quality control containers 360, thereby improving the detection efficiency of the quantitative analyzer 310.

[0085] When the library product is quality controlled, the construction reaction container 350 containing the library construction product is sent to the quality control system 300 for quality control through the library construction operator component 320. That is, when the library is quality controlled, the construction reaction container 350 is sent to the quality control system 300 for quality control through the library construction operator component 320.

[0086] In an achievable solution, the gene sequencing pre-workstation provided in the embodiment of the present application further includes a frame, a workbench 1000 is provided on the frame, and the nucleic acid extraction system, the quality control system and the library construction system are all provided on the workbench 1000. The nucleic acid extraction system, the quality control system and the library construction system are carried by the workbench 1000 so that the three are relatively fixed. The above-mentioned three-axis motion platform can be provided on the frame so as to support the three-axis motion platform through the frame.

[0087] In an optional solution, the nucleic acid sequencing pre-processing workstation also includes an air filter device, which is arranged on the top of the rack. The air filter device is installed on the top of the rack, and has a fan and a high-efficiency filter inside, which can filter and purify the external air and send it into the chassis to provide a clean positive pressure environment in the chassis to prevent aerosol contamination. Correspondingly, the left and right sides of the rack are provided with air outlet fans, and the air volume of the air outlet fans is less than the air volume of the air filter device.

[0088] To facilitate understanding of the principle of the gene sequencing pre-processing workstation provided in the embodiment of the present application, the embodiment of the present application also provides a nucleic acid sequencing pre-processing method, which comprises the following steps:

[0089] Step 001: The nucleic acid extraction system controllably extracts nucleic acid molecules from a biological sample;

[0090] For details, please refer to Figure 1 to Figure 3 The description of the nucleic acid sequencing pre-processing workstation shown in will not be elaborated here.

[0091] Step 002: The quality control system controls the concentration of the library construction product, and according to the detection result, adds a homogenization reagent to the library construction product and dilutes it to the concentration required for nucleic acid sequencing;

[0092] For details, please refer to Figure 1 to Figure 3 The description of the nucleic acid sequencing pre-processing workstation shown in will not be elaborated here.

[0093] Step 003: The library construction system controllably prepares the nucleic acid molecules into a library that can be used for sequencing.

[0094] For details, please refer to Figure 1 to Figure 3 The description of the nucleic acid sequencing pre-processing workstation shown in will not be elaborated here.

[0095] In addition, in addition to the above steps, the method provided in the embodiment of the present application may also include a quality control system that can controllably detect the concentration of the library in the library construction product, and adjust the concentration of the library to a pre-required concentration range according to the detection result. Thus, the quality control system can be used to control the quality of the library, so as to prepare and provide the library required for sequencing on the nucleic acid sequencer.

[0096] Continue to refer Figure 4 to Figure 7 , Figure 4 to Figure 7 A structural reference diagram of a gene sequencing pre-processing workstation provided in an embodiment of the present application is shown.

[0097] In order to facilitate the description of the arrangement of each module (nucleic acid extraction module 10 (i.e., the nucleic acid extraction system 10 in the previous embodiment), quality inspection module 20 (i.e., the quality control system 30 in the previous embodiment), and library construction module 40 (i.e., the library construction system 20 in the embodiment of the present application)), an XYZ coordinate system is constructed, wherein the X direction is perpendicular to the Y direction and the Z direction, and the X direction and the Y direction are parallel to the placement plane of each module.

[0098] To facilitate the transfer of nucleic acid by the first transfer mechanism 30, when the nucleic acid extraction module 10, the quality inspection module 20 and the library building module 40 are arranged, the first transfer mechanism 30 is located between the nucleic acid extraction module 10, the quality inspection module 20 and the library building module 40. Exemplarily, in the specific arrangement, the quality inspection module 20 and the library building module 40 are arranged side by side (arranged along the X direction), and the nucleic acid extraction module 10 is located above the quality inspection module 20 (along the Y direction). When the first transfer mechanism 30 is set, the first transfer mechanism 30 is located between the quality inspection module 20 and the library building module 40, and is opposite to the nucleic acid extraction module 10, that is, the quality inspection module 20, the library building module 40 and the nucleic acid extraction module 10 are arranged around the first transfer mechanism 30, so that the first transfer mechanism 30 can transfer nucleic acid between each module in a smaller path. Among them, the quality inspection module 20 and the first transfer mechanism 30 are part of the quality control system.

[0099] Continue to refer Figure 5 The nucleic acid extraction module 10 provided in the embodiment of the present application is used to extract nucleic acid, and the nucleic acid extraction module 10 can be a multi-channel magnetic bar nucleic acid extraction module 10, which can perform high-quality nucleic acid extraction on multiple samples at the same time. Specifically, the multi-channel magnetic bar nucleic acid extraction module 10 can be a magnetic bar method nucleic acid extractor. The nucleic acid extraction module 10 has an extraction kit 11 (i.e., a nucleic acid extraction operation container), and the extraction kit 11 is used to carry various reagents required for nucleic acid extraction. When in use, the product (containing nucleic acid) extracted by the nucleic acid extraction module 10 is carried by a test tube on the extraction kit 11. When the first transfer mechanism 30 transfers nucleic acid, the product can be sucked from the extraction kit 11 to suck nucleic acid.

[0100] For reference Figure 5 and Figure 6 The quality inspection module 20 provided in the embodiment of the present application mainly includes a first pipette tip box 21 (placed in the pipette tip storage area), a quality inspection reagent kit 22 (i.e., a detection reagent container 370), a quality inspection tube rack 23, a fluorescence quantitative instrument 24 (i.e., a quantitative analyzer 310), and a quality inspection plate position 25 (accommodating a reaction plate, which is a reaction container 350); wherein the first pipette tip box 21 is used to carry a pipette tip, which is used to cooperate with the first transfer mechanism 30 to absorb nucleic acids or reagents through the pipette tip. The quality inspection tube rack 23 is used to carry a quality inspection tube (i.e., a quality control container, which is a test tube or other tubular structure that can carry nucleic acids), which is used to carry nucleic acids and reagents. The quality inspection reagent kit 22 is used to carry quality inspection and homogenization reagents, the fluorescence quantitative instrument 24 is used to perform quality inspection on nucleic acids, and the quality inspection plate position 25 is used as a transfer structure to transfer the quality-inspected nucleic acids to the consumable "reaction plate".

[0101] When the above-mentioned first pipette tip box 21, quality inspection tube rack 23, quality inspection reagent kit 22, quality inspection board position 25 and fluorescence quantifier 24 are specifically arranged, the first pipette tip box 21, quality inspection reagent kit 22 and quality inspection board position 25 are arranged in a single row, which are specifically arranged along the X direction. In the specific arrangement, the first pipette tip box 21 is located at the far left, the quality inspection board position 25 is located at the far right, and the quality inspection reagent kit 22 is located between the two. The fluorescence quantifier 24 and the quality inspection tube rack 23 are arranged in a single row, which are specifically arranged along the X direction. In the specific arrangement, the fluorescence quantifier 24 is located on the left, the quality inspection tube rack is located on the right, and the fluorescence quantifier 24 and the quality inspection tube rack 23 are located below the first pipette tip box 21. In the specific arrangement, the nucleic acid extraction module 10 is located above the quality inspection reagent kit 22 and the first pipette tip box 21, and the first transfer mechanism 30 is arranged between the quality inspection reagent kit 22 and the quality inspection board position 25. When arranged in the above manner, the first transfer mechanism 30 can absorb the tips in the first tip box 21 through a shorter path and absorb the product in the extraction kit 11 in the nucleic acid extraction module 10. At the same time, the quality inspection reagent and the homogenization reagent (such as ultrapure water) in the quality inspection kit 22 can also be absorbed through a smaller path.

[0102] Continue to refer Figure 6 and Figure 7, the first transfer mechanism 30 provided in the embodiment of the present application includes: a reciprocating motion device 35 (i.e., a conveying mechanism 330), a single-channel pipette 33 (i.e., a quality control pipetting assembly 340) and a rotating clamp 34 (i.e., a quality control operating hand assembly 320). Among them, the reciprocating motion device 35 is used to carry the quality inspection tube to move, and it includes an annular conveyor belt 352 located on one side of the quality inspection reagent box 22 and the quality inspection tube rack 23, and two holes 351 fixed at intervals on the annular conveyor belt 352. When carrying the quality inspection tube, the quality inspection tube can be placed on the hole 351. When the above-mentioned annular conveyor belt 352 is arranged, the length direction of the annular conveyor belt 352 is along the Y direction, and the annular plane formed by it is parallel to the placement plane of the nucleic acid extraction module 10 and the quality inspection module 20. The annular conveyor belt 352 is located between the quality inspection reagent box 22 and the quality inspection plate position 25. When the annular conveyor belt 352 rotates, it can drive the two holes 351 to move between the quality inspection reagent box 22 and the quality inspection tube rack 23. That is, the nucleic acid extraction module 10, the quality inspection reagent kit 22, the quality inspection tube rack 24, and the quality inspection plate position 25 are all located outside the circular conveyor belt 352, so that the quality inspection tube can be transplanted through a smaller moving path during transplantation.

[0103] When moving the quality inspection tube, the quality inspection tube is grasped by the rotating clamp 34. The rotating clamp 34 is used to transfer the quality inspection tube between the quality inspection tube rack 23, the reciprocating motion device 35 and the fluorescence quantitative instrument 24, and can be used to open or close the quality inspection tube. Specifically, the rotating clamp 34 is used to transplant the quality inspection tube on the quality inspection tube rack 23 to a hole 351 on the circular conveyor 352, so that the quality inspection tube can be placed on the hole 351. In addition, the rotating clamp 34 is also used to transplant the quality inspection tube loaded with reagents to the fluorescence quantitative instrument 24, and to transplant the quality inspection tube that has completed the fluorescence quantitative detection to the quality inspection tube rack 23. In order to realize the transfer of the quality inspection tube between the reciprocating motion device 35, the fluorescence quantitative instrument 24 and the quality inspection tube rack 23.

[0104] When sucking nucleic acid or homogenizing reagent, the quality inspection tube can be opened by rotating the clamp 34, and then realized by the single-channel pipette 33. The single-channel pipette 33 can be used to suck the pipette tip from the first pipette tip box 21, and transfer liquid on the extraction reagent kit 11, the reciprocating motion device 35, the quality inspection reagent kit 22 and the quality inspection plate position 25 of the nucleic acid extraction module 10. When implemented, the single-channel pipette 33 sucks the pipette tip from the first pipette tip box 21, and sucks the extraction product from the extraction reagent kit 11 of the nucleic acid extraction module 10, and adds it to the quality inspection tube carried in the hole position 351. It is also used to add the homogenizing reagent in the quality inspection reagent kit 22 to the quality inspection tube carried in the hole position 351. Then the quality inspection tube is closed by rotating the clamp 34.

[0105] It should be understood that in a specific embodiment, the rotating jaw 34 and the single-channel pipette 33 are respectively carried on two different three-axis motion platforms. For the convenience of description, the one carrying the single-channel pipette 33 is named the first three-axis motion platform 31, and the one carrying the rotating jaw 34 is named the second three-axis motion platform 32. The first three-axis motion platform 31 and the second three-axis motion platform 32 can move in the XYZ direction, wherein the Z direction is perpendicular to the X direction and the Y direction. When the rotating jaw 34 and the single-channel pipette 33 are in use, they can be moved to the corresponding operating position by the first three-axis motion platform 31 and the second three-axis motion platform 32. Exemplarily, the first three-axis motion platform 31 and the second three-axis motion platform 32 may include tracks parallel to the X direction, the Y direction and the Z direction, respectively, and each track is slidably connected to each other.

[0106] When the extraction product is transferred to the quality inspection module 20 for inspection through the first transfer mechanism 30, the specific process is as follows: add the quality inspection reagent to the quality inspection tube, add the extraction product to the quality inspection tube and blow to mix, detect the mixture in the quality inspection tube to obtain the quality inspection result, and then add the extraction product and the homogenization reagent to the reaction plate according to the quality inspection result and the library loading parameters.

[0107] When adding the quality inspection reagent to the quality inspection tube, the first quality inspection tube is transferred from the quality inspection tube rack 23 to the hole of the reciprocating motion device 35 by the rotating claw 34 of the first transfer mechanism 30, the tube cover is rotated to open, and the tube cover is put back into the hole of the quality inspection tube rack 23;

[0108] The first quality inspection tube is moved to the working position of the single-channel pipette 33 by the reciprocating motion device 35; the single-channel pipette 33 is used to load the pipette tip in the first pipette tip box, and the quality inspection reagent is sucked from the quality inspection reagent kit 22 and added to the first quality inspection tube; then the first transfer mechanism 30 puts the first quality inspection tube back to the quality inspection tube rack 23, so that the reciprocating motion device 35 can be used to add the quality inspection reagent to the second quality inspection tube, the third quality inspection tube and more quality inspection tubes in turn, and the first transfer mechanism 30 can be used to put the second quality inspection tube, the third quality inspection tube and more quality inspection tubes back to the quality inspection tube rack 23. During this process, the nucleic acid extraction module 10 completes the extraction of nucleic acid to generate an extraction product, and the extraction product is located in the elution hole in the extraction reagent kit 11.

[0109] Afterwards, when the extraction product is added to the quality inspection tube and mixed by pipetting, the first quality inspection tube containing the quality inspection reagent is placed in the hole of the reciprocating motion device 35 by the first transfer mechanism 30. The single-channel pipette 33 is used to load the pipette tip in the first pipette tip box and suck the extraction product from the corresponding elution hole on the extraction reagent kit 11, and add it to the first quality inspection tube and mix it by pipetting;

[0110] The second quality inspection tube is transferred from the quality inspection tube rack 23 to another hole position of the reciprocating motion device 35 by rotating the clamp 34, and the tube cover is rotated to open; the first quality inspection tube is moved to the position of the rotating clamp 34 by the reciprocating motion device 35, and the tube cover of the second quality inspection tube is covered on the first quality inspection tube; and the first quality inspection tube is moved to the hole position of the quality inspection tube rack by rotating the clamp 34;

[0111] After the first set time interval, the third quality inspection tube is grabbed from the quality inspection tube rack 23 by rotating the clamp 34 and placed in the hole of the reciprocating motion device 35; at the same time, the second quality inspection tube is loaded with the extraction product by the single-channel pipette 33 and mixed by pipetting;

[0112] After the first quality inspection tube is incubated for the second set time, the hatch of the fluorescence quantitative instrument 24 is opened, and during the interval, the first quality inspection tube is placed in the fluorescence quantitative instrument 24 by rotating the clamp 34 for detection, and after the detection is completed, the first quality inspection tube is taken out of the fluorescence quantitative instrument 24 by the rotating clamp 34 and put back to the corresponding position of the quality inspection tube rack 23;

[0113] The incubated second quality inspection tube and the third quality inspection tube are sequentially sent to the fluorescence quantitative instrument 24 for quality inspection, and then sent to the quality inspection tube rack 23 after the quality inspection.

[0114] It can be seen from the above description that the rotating jaws 34 and the single-channel pipette 33 cooperate with the reciprocating motion device 35 to open the caps, transfer, add liquid, etc. of multiple quality inspection tubes. And for any quality inspection tube, the rotating jaws 34, the single-channel pipette 33 and the reciprocating motion device 35 disclosed in the embodiment of the present application are not sent to the fluorescence quantitative instrument 24 after the quality inspection reagents and the extraction products are added and mixed by blowing and resting, and then another quality inspection tube is operated. Instead, another quality inspection tube is operated during the time interval of transfer, addition or rest of the quality inspection tube to improve the efficiency of the whole process.

[0115] Exemplarily, during the extraction product quality inspection operation, the rotating clamp 34 transfers the No. 1 quality inspection tube from the quality inspection tube rack 23 to the hole 351 of the reciprocating motion device, and rotates to open the cover, and the rotating clamp 34 puts the tube cover back into the No. 1 hole of the quality inspection tube rack 23. At the same time, the reciprocating motion device 35 moves the quality inspection tube to the working position of the single-channel pipette 33 (the position of the quality inspection reagent kit 22), and the single-channel pipette 33 loads a pipette tip in the first pipette tip box 21, and absorbs the quality inspection reagent from the quality inspection reagent kit 22 and adds it to the quality inspection tube; then the first transfer mechanism 30 puts the quality inspection tube back to the quality inspection tube rack 23. In this way, the operation of adding quality inspection reagents to multiple quality inspection tubes is completed. In this process, the nucleic acid extraction module 10 completes the extraction of nucleic acid to generate extraction products, and the extraction products are located in the extraction reagent kit 11. Afterwards, the first transfer mechanism 30 places the quality inspection tube containing the quality inspection reagent into the hole of the reciprocating device 35 again, and the single-channel pipette 33 absorbs the extraction product from the elution hole of the pipette extraction reagent kit 11 loaded in the first pipette box, and transfers it to the quality inspection tube in the corresponding hole 351 of the reciprocating device, and blows and mixes it. At the same time, the rotating clamp 34 grabs the No. 2 quality inspection tube from the quality inspection tube rack 23, transfers it to the hole 351 of the reciprocating device, and rotates to open the cover. After that, the pipette tip is returned to its original position, and the reciprocating device 35 transfers the quality inspection tube to the operating position of the rotating clamp 34. The rotating clamp 34 screws the tube cover of the No. 2 quality inspection tube onto the No. 1 quality inspection tube, and transfers the No. 1 quality inspection tube to the No. 2 hole of the quality inspection tube rack 23. After a certain period of time, the rotating clamp 34 grabs the No. 3 quality inspection tube from the quality inspection tube rack 23 and places it in the hole 351 of the reciprocating device. During the time of closing the lid and grabbing a new tube, the single-channel pipette 33 loads the sample into the No. 2 quality inspection tube and mixes it by blowing, and the cycle repeats. After the No. 1 quality inspection tube is incubated for an appropriate time, the door of the fluorescence quantitative instrument 24 is opened, and the rotating clamp 34 grabs the quality inspection tube and puts it into the fluorescence quantitative instrument 24 during the interval, and the door of the fluorescence quantitative instrument 24 is closed. The host computer issues a detection instruction, and the fluorescence quantitative instrument 24 transmits the data to the host computer for storage and processing after detection. At the same time, the door of the fluorescence quantitative instrument 24 is opened, and the rotating clamp 34 takes the quality inspection tube out of the fluorescence quantitative instrument 24 and puts it back to the corresponding position of the quality inspection tube rack 23, and the cycle repeats. In the above scheme, the transfer of each quality inspection tube and the intervals of adding liquid and being still are used to operate multiple quality inspection tubes, so that the first transfer mechanism 30 can reasonably use the time difference to increase the operating efficiency of the quality inspection tube, thereby improving the detection efficiency of the fluorescence quantitative instrument 24.

[0116] After the extraction product quality inspection is completed, according to the quality inspection results and the library loading parameters, a certain proportion of nucleic acid and homogenization reagent are sucked from the elution well of the extraction kit 11 and the quality inspection kit 22 by the single-channel pipette 33, and added to the consumable "reaction plate" on the quality inspection plate position 25. The product quality inspection process after library construction is the same as above, except that the sample suction position is changed from the extraction kit 11 to the quality inspection plate position 25; during the homogenization operation, according to the concentration quality inspection data in the host computer, the homogenization reagent in the quality inspection kit 22 is sucked by the single-channel pipette 33, and added to the consumable "reaction plate" on the quality inspection plate position 25, and the library construction product is diluted to the concentration required for sequencing.

[0117] In an implementable solution, the two holes 351 are arranged at intervals. The two holes 351 are arranged at positions such that when the quality inspection tube carried by one of the holes 351 is loaded with nucleic acid, the other hole 351 can be moved to the working area of ​​the rotating jaw 34, so that the movements of the rotating jaw 34 and the single-channel pipette 33 do not interfere with each other, so as to make full use of the time for the single-channel pipette 33 to load the sample and mix by pipetting, and use the rotating jaw 34 to perform operations such as opening and closing the cover and transferring the quality inspection tube, thereby improving the efficiency of detection.

[0118] For reference Figure 5 and Figure 8, the library construction module provided in the embodiment of the present application is used to construct a library for nucleic acid. The library construction module 40 provided in the embodiment of the present application mainly includes: a second pipette tip box 41 (placed in the pipette tip storage area), a reagent kit 42 (i.e., a large-capacity reagent container 290), an oscillation module 43 (i.e., an oscillation heating component 250), a sample adding plate position 45 (i.e., a reagent adding area), a magnetic rack 46 (i.e., a magnet assembly 260), a refrigeration module 48 (accommodating the library construction reagent container 240) and a second transfer mechanism 50. Among them, the second pipette tip box 41 is used to carry pipette tips; the reagent kit 42 is used to carry large-volume reagents required for library construction, the sample adding plate position 45 is used to maintain a low temperature environment when adding reagents to the consumable "reaction plate" to prevent the reagents from reacting prematurely, and the refrigeration module 48 can refrigerate and store the key reagents required for library construction to prevent deterioration; the magnetic rack 46 and the oscillation module 43 are used to purify the nucleic acids with magnetic beads to meet the requirements of efficient magnetic bead purification during library construction. Specifically, the reagent box 42, the magnetic rack 46 and the oscillation module 43 are used for magnetic bead purification during the library construction process. The second transfer mechanism 50 is used to flexibly transfer the consumables (the consumables include at least a reaction plate and a purification plate) between the quality inspection plate position 25 (accommodating the reaction plate, which is the reaction vessel 350), the sample loading plate position 45, the thermal cycle module 47 (i.e., the PCR instrument 210), the magnetic rack 46, and the oscillation module 43, and is used to load the reagents in the refrigeration module 48 and the reagent box 42 into the consumables "reaction plate" and "purification plate" (i.e., purification container). The functions of the above-mentioned second pipette tip box 41, the reagent box 42, the refrigeration module 48, the magnetic rack 46, and the oscillation module 43 are all conventional modules in the library construction module, and will not be described in detail in the embodiments of the present application.

[0119] In addition, the library building module 40 provided in the embodiment of the present application may also include a thermal cycle module 47, which is fixed to the workbench 1 and is used to provide fast and high-precision temperature control for the library building module. In the specific setting, the thermal cycle module 47 is also located at the corner of the workbench 1, and an air outlet fan 301 is provided on the right side thereof to quickly extract the generated aerosol to reduce the risk of contamination.

[0120] In addition, the library building module 40 also includes a waste box 44 (i.e., a waste container 280), which is used to hold waste generated during the library building process. In the specific setting, the waste box 44 is arranged diagonally with the nucleic acid extraction module 10, so that the space can be reasonably utilized. In addition, the waste box 44 is located at a corner position, which is also relatively far away from other modules. Reduce the probability of waste contaminating other substances.

[0121] Continue to refer Figure 5 , Figure 7 and Figure 8As shown in FIG. 4 , when the various positions in the library building module 40 are specifically arranged, the second pipette tip box 41, the reagent kit 42, the shaking module 43, the waste box 44, the sample loading position 45, the magnetic rack 46, the thermal cycle module 47, and the refrigeration module 48 are arranged in an array. Figure 5 As shown in the figure, the second pipette tip box 41, the reagent kit 42, the shaking module 43, the waste box 44, the sample loading plate 45, the magnetic rack 46, the thermal cycle module 47, and the refrigeration module 48 are arranged in an array, which forms a step structure as a whole to avoid the structures in the nucleic acid extraction module 10 and the quality inspection module 20, so that the various plate positions of the workstation form an overall structure of array arrangement on the placement surface.

[0122] In a specific configuration, the second pipette tip boxes 41 are arranged in multiple rows and in a stepped arrangement. The stepped arrangement formed by the second pipette tip boxes 41 avoids the nucleic acid extraction module 10, the quality inspection module 20 and the refrigeration module 44. Figure 5 As shown in , the second pipette tip boxes 41 are arranged in three rows, each row is arranged in the Y direction, and multiple rows of second pipette tip boxes 41 are arranged in the X direction. Along the X direction, there is one second pipette tip box 41 in the first row, five second pipette tip boxes 41 in the second row, and three second pipette tip boxes 41 in the third row, thereby forming a stepped arrangement. When cooperating with the quality inspection module 20 and the nucleic acid extraction module 10, the second pipette tip boxes 41 in the first row and the quality inspection plate position 25 are arranged in a row along the Y direction. The second pipette tip boxes 41 in the second and third rows are located on one side of the nucleic acid extraction module 10, so that the space can be reasonably utilized, the nucleic acid extraction module 10, the quality inspection module 20 and the library construction module 40 are integrated on a placement surface, and the three modules are arranged closely.

[0123] The refrigeration module 48 has multiple Figure 5 As shown in the figure, there are four refrigeration modules 42, and the four refrigeration modules 48 are arranged in a row of two along the Y direction, with a total of two rows. They are located on the right side of the second suction head box 41 in the second row and above the second suction head box 41 and the sample loading plate position 45 in the third row.

[0124] The sample loading plate 45, the reagent kit 42, and the shaking module 43 are arranged in a row along the Y direction, and in order from top to bottom, they are the sample loading plate 45, the reagent kit 42, and the shaking module 43. The thermal cycle module 47 and the magnetic rack 46 are arranged in a row along the Y direction, and in order from top to bottom, they are the thermal cycle module 47 and the magnetic rack 46.

[0125] During the library construction process, the consumables "reaction plate" and "purification plate" can be transferred between the quality inspection plate position 25, the sample loading plate position 45, the thermal cycle module 47, the magnetic rack 46, and the shaking module 43 through the second transfer mechanism 50, and the reagents in the refrigeration module 48 and the reagent kit 43 can be loaded into the consumables "reaction plate" and "purification plate".

[0126] In a specific configuration, the second transfer mechanism 50 includes a multi-channel pipette 52, which is used to absorb the tips in the second tip box 41 and to transfer liquids in each plate position of the library building module.

[0127] In specific use, the second transfer mechanism 50 includes a three-axis motion platform, which is named the third three-axis motion platform 51 for the convenience of description. The third three-axis motion platform 51 can realize movement in the X direction, the Y direction and the Z direction. In addition, the second transfer mechanism 50 also includes a turntable clamp 53 (i.e., the library construction manipulator assembly 220) arranged on the third three-axis motion platform 51; the multi-channel pipette 52 (i.e., the library construction pipetting assembly 230) is also arranged on the third three-axis motion platform 51. Among them, the turntable clamp 53 can flexibly transfer the consumables "reaction plate" and "purification plate" between the quality inspection plate position 25, the sample adding plate position 45, the thermal cycle module 47, the magnetic stand 46, and the oscillation module 43.

[0128] In an optional solution, the library building module also includes an information acquisition module 54 provided on the multi-channel pipette 52, and the information acquisition module 54 is used to collect information of the test kit when the pipette collects reagents. And the information is uploaded to the host computer to realize the collection of information. In addition, the information acquisition module 54 can also collect information of consumables and position information of the motion mechanism (second transfer mechanism 50) at the same time. The host computer determines whether the consumables are misplaced or missed based on the information collected by the information acquisition module 54, and calibrates the position deviation of the motion mechanism based on the information collected by the information acquisition module 54. It should be understood that the above-mentioned host computer performs actions based on the information collected by the information acquisition module 54, which is a conventional control method in the field and will not be repeated here.

[0129] In order to carry the above-mentioned modules, the workstation provided in the embodiment of the present application also includes a frame 2, on which a workbench 1 is arranged, and the above-mentioned nucleic acid extraction module 10, quality inspection module 20 and library building module 40 are all arranged on the workbench 1. The above-mentioned modules can be carried by the workbench 1. In addition, the three-axis motion platform in the first transfer mechanism 30 and the second transfer mechanism 50 can be supported by the frame 2, and the rotating plate clamp 53 and the rotating clamp 33 are suspended above the workbench 1, so that the quality inspection tube can be clamped and moved between different modules.

[0130] The rack 2 is also provided with a sealed door 201. The sealed door 201 and the rack instrument isolate the air inside the instrument from the outside of the instrument, thereby preventing sample contamination caused by the external environment, and also preventing the nucleic acid inside the instrument from contaminating the external environment.

[0131] In an optional solution, the workstation further includes an air filter device 3, which is arranged on the top of the rack 2. The air filter device 3 is installed on the top of the rack 2, and has a fan and a high-efficiency filter inside, which can filter and purify the external air and send it into the chassis to provide a clean positive pressure environment in the chassis to prevent aerosol pollution. Correspondingly, the left and right sides of the rack 2 are provided with air outlet fans 301, and the air volume of the air outlet fans 301 is smaller than the air volume of the air filter device 3.

[0132] To facilitate understanding of the workstation provided in the embodiment of the present application, the embodiment of the present application further provides a method for constructing a nucleic acid library, the method utilizing any of the above-described workstations; the method comprising the following steps:

[0133] Step 001: extracting nucleic acid through the nucleic acid extraction module and forming an extraction product;

[0134] Specifically, refer to Figures 4 to 8 The relevant description in will not be repeated here.

[0135] Step 002: transferring the extracted product to the quality inspection module for quality inspection through the first transfer mechanism;

[0136] Specifically, the following steps are included:

[0137] Step a, adding quality inspection reagent to the quality inspection tube;

[0138] Specifically, the quality inspection tube is transferred from the quality inspection tube rack to the hole position of the reciprocating motion device by the rotating clamp of the first transfer mechanism, and the tube cover is rotated to open;

[0139] The quality inspection tube is moved to the working position of the single-channel pipette by the reciprocating motion device; the tips are loaded into the first tip box by the single-channel pipette, and the quality inspection reagent is sucked from the quality inspection reagent kit and added into the quality inspection tube; then the first transfer mechanism puts the quality inspection tube back into the quality inspection tube rack;

[0140] Repeat the above steps until the quality inspection reagent is added to a predetermined number of quality inspection tubes.

[0141] Step b, adding the extracted product to the quality inspection tube and mixing by pipetting;

[0142] Specifically, the first quality inspection tube is placed in the hole of the reciprocating motion device through the first transfer mechanism, the tube cover is rotated to open, and the tube cover is put back into the hole of the quality inspection tube rack; the single-channel pipette is loaded with a pipette tip in the first pipette tip box and the extraction product is sucked from the corresponding elution hole on the extraction kit, and added to the first quality inspection tube by pipetting and mixing;

[0143] The second quality inspection tube is transferred from the quality inspection tube rack to another hole position of the reciprocating motion device by rotating the clamp, and the tube cover is rotated to open; the first quality inspection tube is moved to the position of the rotating clamp by the reciprocating motion device, and the tube cover of the second quality inspection tube is covered on the first quality inspection tube; and the first quality inspection tube is moved to the hole position of the quality inspection tube rack by rotating the clamp;

[0144] After the first set time interval, the third quality inspection tube is grabbed from the quality inspection tube rack by rotating the clamp and placed in the hole of the reciprocating motion device; at the same time, the extraction product is sucked from the corresponding elution hole on the extraction kit by a single-channel pipette and added to the second quality inspection tube, and mixed by blowing;

[0145] Repeat the above steps until the predetermined number of quality control tubes are added with the extraction products of the corresponding elution wells and mixed by pipetting.

[0146] Step c, testing the mixed material in the quality inspection tube to obtain a quality inspection result;

[0147] Specifically, after the first quality inspection tube is incubated for a second set time, the hatch of the fluorescence quantitative instrument is opened, and during the interval, the first quality inspection tube is placed in the fluorescence quantitative instrument for detection by the rotating clamp, and after the detection is completed, the first quality inspection tube is taken out of the fluorescence quantitative instrument by the rotating clamp and placed back in the corresponding position of the quality inspection tube rack;

[0148] Repeat the above steps until the quality inspection of the predetermined number of quality inspection tubes is completed.

[0149] Step d: adding the extraction product and the homogenization reagent to the reaction plate according to the quality inspection results and the library loading parameters.

[0150] According to the quality inspection results of each quality inspection tube and the library loading parameters, the single-channel pipette draws a certain proportion of the extraction product and the homogenization reagent from the elution wells corresponding to the extraction kit and the quality inspection kit, respectively, and adds them to the corresponding wells on the reaction plate on the quality inspection plate.

[0151] Specific references Figures 4 to 8 The relevant description in will not be repeated here.

[0152] Step 003: The nucleic acid after quality inspection in the quality inspection module is transferred to the library construction module through the second transfer mechanism for library construction.

[0153] Specifically, refer to Figures 4 to 8 The relevant description in will not be repeated here.

[0154] In the above technical scheme, through the cooperation of the nucleic acid extraction module, the quality inspection module, the library construction module and the first transfer mechanism, operations such as nucleic acid extraction, quality inspection, library construction, quality inspection, and homogenization are realized, the degree of automation of library construction is improved, and then the consistency of the library is improved, and the impact of external risks on the test results is reduced.

[0155] One or more embodiments of this specification are intended to cover all such substitutions, modifications and variations that fall within the broad scope of the appended claims. Therefore, any omissions, modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of one or more embodiments of this specification should be included in the scope of protection of this disclosure.

[0156] The above are only specific implementations of the present application, but the protection scope of the present application is not limited thereto. Any technician familiar with the technical field can easily think of changes or substitutions within the technical scope disclosed in the present application, which should be included in the protection scope of the present application. Therefore, the protection scope of the present application should be based on the protection scope of the claims.

Claims

1. A nucleic acid sequencing pre-processing workstation, characterized in that: include: A nucleic acid extraction system configured to controllably extract nucleic acid molecules from a biological sample; A library construction system configured to controllably prepare the nucleic acid molecules into a library that can be used for sequencing; The quality control system is configured to controllably detect the concentration of the nucleic acid extraction product and add a homogenizing agent to the nucleic acid extraction product according to the detection result and the library construction loading parameter; and / or controllably detect the concentration of the library construction product and add a homogenizing agent to the library construction product according to the detection result and dilute it to the concentration required for nucleic acid sequencing.

2. The nucleic acid sequencing pre-processing workstation according to claim 1, characterized in that: The quality control system includes a quantitative analyzer, a quality control operator component, a transmission mechanism, a quality control pipetting component, a reaction container, a quality control container and a detection reagent container; The quality control container is configured to accommodate the nucleic acid extraction product or library construction product to be detected, and can be placed in the quantitative analyzer to realize concentration detection; The detection reagent container is configured to accommodate one or more detection reagents required for the quantitative analyzer to perform concentration detection and reagents for adjusting the concentration of nucleic acid extraction products and / or library construction products; The conveying mechanism is configured to reciprocate the quality control container between the working area of ​​the quality control operating hand assembly and the working area of ​​the quality control pipetting assembly; The quality control operator assembly is configured to take out the quality control container from the storage area of ​​the quality control container and place it on the conveying mechanism, take out the quality control container from the conveying mechanism and put it back to the storage area of ​​the quality control container, take out the quality control container from the storage area of ​​the quality control container and put it into the quantitative analyzer, take out the quality control container that has completed the test from the quantitative analyzer and put it back to the storage area of ​​the quality control container; The quality control pipetting component is configured to draw a certain amount of detection reagent from the detection reagent container and add it to the quality control container, and to draw a certain amount of reagent for adjusting the concentration of nucleic acid extraction products and / or library construction products and add it to the construction reaction container; The construction reaction container is configured to accommodate the nucleic acid extraction product after quality control and provide a reaction space for the library construction process.

3. The nucleic acid sequencing pre-processing workstation according to claim 2, characterized in that: The conveying mechanism includes a conveyor belt and at least two accommodating positions fixed on the conveyor belt for accommodating the quality control container; wherein, The conveyor belt is configured to reciprocate the quality control container between the working area of ​​the quality control operating hand assembly and the working area of ​​the quality control pipetting assembly.

4. The nucleic acid sequencing pre-processing workstation according to claim 3, characterized in that: The library construction system includes a PCR instrument, a library construction operator component, a library construction pipetting component, a library construction reagent container, an oscillating heating component and a magnet component; The library construction operator component is configured to take out the construction reaction container containing the nucleic acid extraction product after quality control from the quality control system, place the construction reaction container in the reagent adding area of ​​the library construction system, and send the construction reaction container loaded with reagents to the PCR instrument; and / or, sending the construction reaction container containing the library construction product to the quality control system for quality control; The library construction reagent container is configured to contain one or more library construction reagents required for library construction; The magnet assembly is configured to provide a necessary magnetic field environment for magnetic bead purification; The oscillating heating component is configured to provide a reaction space and reaction temperature for magnetic bead purification during library construction; The library construction pipetting component is configured to add library construction reagents from the library construction reagent container to the construction reaction container.

5. The nucleic acid sequencing pre-processing workstation according to claim 4, characterized in that: Also included is a waste container for receiving discarded pipetting tips of the library preparation pipetting assembly.

6. The nucleic acid sequencing pre-processing workstation according to any one of claims 1 to 5, characterized in that: It also includes a frame, on which a workbench is arranged, and the nucleic acid extraction system, the quality control system and the library construction system are all arranged on the workbench.

7. The nucleic acid sequencing pre-processing workstation according to claim 6, characterized in that: When the library construction system includes a library construction manipulator component and a library construction pipetting component, the library construction manipulator component and the library construction pipetting component are arranged on the same three-axis motion platform, and the three-axis motion platform is arranged on the frame.

8. The nucleic acid sequencing pre-processing workstation according to claim 7, characterized in that: It also includes an information acquisition module disposed on the three-axis motion platform, and the information acquisition module is used to acquire information about consumables in the nucleic acid sequencing pre-processing workstation.

9. The nucleic acid sequencing pre-processing workstation according to claim 6, characterized in that: It also includes an air filter device, which is arranged on the top of the frame.

10. A nucleic acid sequencing pre-treatment method, characterized in that: The method comprises: The nucleic acid extraction system can controllably extract nucleic acid molecules from biological samples; The quality control system can controllably detect the concentration of the nucleic acid extraction product and add a homogenizing agent to the nucleic acid extraction product according to the detection result and the library construction loading parameter; the library construction system can controllably prepare the nucleic acid molecules into a library for sequencing.

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