Synchronous buffering magnetic plate, library construction system and gene sequencing pretreatment system

Abstract

The utility model provides a synchronous buffering magnetic plate, a library construction system and a gene sequencing pretreatment system, and relates to the technical field of gene sequencing pretreatment, and the synchronous buffering magnetic plate comprises a magnet pore plate, a base, a buffering mechanism and a synchronizing mechanism; the magnet hole plate is connected with the base through the buffering mechanism and the synchronizing mechanism, the buffering mechanism is of a flexible supporting structure, the synchronizing mechanism comprises a fixed end and a movable end, the fixed end is rotatably fixed to the base, the movable end is connected with the two ends of the magnet hole plate, and the magnet hole plate is connected with the base through the buffering mechanism and the synchronizing mechanism. The two ends of the magnet hole plate are driven to act synchronously. According to the technical scheme, the technical problem that in the prior art, due to the fact that a magnetic plate is pressed to incline, the pipetting effects of different columns of magnetic plate pore plates are different is solved.

Description

TECHNICAL FIELD

[0001] The application relates to the technical field of gene sequencing pretreatment, in particular to a synchronous buffering magnetic plate, a library construction system and a gene sequencing pretreatment system. BACKGROUND

[0002] In a pipetting workstation for gene sequencing pretreatment, a magnetic plate is a commonly used magnetic bead purification tool. During the purification process, the magnetic plate hole plate needs to be placed on the magnetic plate for multiple times to adsorb the magnetic beads in the hole to the vicinity of the magnetic pole of the magnet, and then a multichannel pipette is used to remove the supernatant. Whether the supernatant is removed completely in this step is related to the quality of the entire purification process. In order to remove the supernatant more completely, the pipette tip will be inserted into the bottom of the magnetic plate hole plate hole as much as possible. During this process, due to the size error between the tip and the magnetic plate hole plate, the tip will inevitably come into contact with the hole bottom, thereby causing the tip to block the hole and leading to pipetting failure or even tip deformation. The magnetic plates on the market are divided into buffered and non-buffered types. The non-buffered structure is hard connected, and the pipetting effect is poor. The buffered structure adopts four compression springs at four corners. When the tip comes into contact with the magnetic plate hole plate, the springs are pressed downward. However, if only one side of the magnetic plate hole plate is pressed downward, the hole plate will be inclined, thereby causing the pipetting effect of different columns of the magnetic plate hole plate to be different. SUMMARY

[0003] The application provides a synchronous buffering magnetic plate, a library construction system and a gene sequencing pretreatment system to solve the technical problem that the pipetting effect of different columns of the magnetic plate hole plate is different due to the inclination of the magnetic plate caused by pressure. The preferred technical solutions in the many technical solutions provided by the application can produce many technical effects, which are described in detail below.

[0004] To achieve the above-mentioned purpose, in one aspect, the application provides a synchronous buffering magnetic plate, which comprises a magnet hole plate, a base, a buffering mechanism and a synchronous mechanism. The magnet hole plate is connected with the base through the buffering mechanism and the synchronous mechanism. The buffering mechanism is a flexible support structure. The synchronous mechanism comprises a fixed end and a movable end. The fixed end is rotatably fixed on the base. The movable end is connected with both ends of the magnet hole plate to drive the two ends of the magnet hole plate to move synchronously.

[0005] Optionally, the fixed end of the synchronous mechanism comprises a torsion bar, and the two ends of the torsion bar are rotatably arranged on the base. The movable end comprises two swing arms. One end of each of the two swing arms is fixedly connected with the two ends of the torsion bar. The other end of each of the two swing arms, which is away from the torsion bar, is connected with the magnet hole plate.

[0006] Optionally, an elongated hole is provided at the end of the swing arm away from the torsion bar, with the long side of the elongated hole being arranged in a horizontal direction. A connecting pin is provided on the magnet plate corresponding to the elongated hole, and the connecting pin passes through the elongated hole to connect the swing arm and the magnet plate.

[0007] Optionally, the base has a mounting groove, the torsion bar is disposed in the mounting groove, the torsion bar is cylindrical, and top blocks are disposed above both ends of the torsion bar, the top blocks rotatably confining the torsion bar within the mounting groove.

[0008] Optionally, four buffer mechanisms are provided, each supported at one of the four corners of the magnetic perforated plate, and the movable end of the synchronization mechanism is connected to the middle position of both ends of the magnetic perforated plate.

[0009] Optionally, the buffer mechanism includes a limiting screw and a buffer spring. The buffer spring supports the magnetic perforated plate on the base, and the limiting screw passes through the magnetic perforated plate and the buffer spring to fix it to the base, limiting the highest position of the magnetic perforated plate.

[0010] Optionally, a limiting block is also provided on the magnet plate, located above the limiting screw and at a set distance from the top surface of the limiting screw, to limit the lowest position of the magnet plate.

[0011] Optionally, the top block is fixed in the mounting groove, and the end face of the top block that presses against the torsion bar is an inclined surface.

[0012] Optionally, the two ends of the torsion bar are square, and the torsion bar is snapped into the corresponding hole on the swing arm through its square end, and fixedly connected to the swing arm by screws.

[0013] On the other hand, this application provides a library construction system, including a synchronous buffer magnetic plate as described in any of the above.

[0014] On the other hand, this application provides a gene sequencing preprocessing system, including the library construction system described above.

[0015] The technical solution of this application may include the following beneficial effects:

[0016] The application provides a synchronous buffering magnetic force plate, which is supported by a buffering mechanism and a synchronous mechanism, the flexible support structure of the buffering mechanism provides buffering when the magnetic hole plate is pressed, the movable end of the synchronous mechanism is connected with both ends of the magnetic hole plate, and the both ends of the magnetic hole plate are synchronously moved, so that the problem that the magnetic hole plate is inclined when being pressed is solved, and the poor pipetting effect caused by the inclination is avoided. BRIEF DESCRIPTION OF DRAWINGS

[0017] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the following will briefly introduce the drawings needed to be used in the embodiments or the prior art description. Obviously, the drawings in the following description are only some embodiments of the present application, and other drawings can be obtained by those skilled in the art without creative labor on the basis of these drawings.

[0018] Figure 1 is a nucleic acid extraction process schematic diagram provided by the embodiment of the present application;

[0019] Figure 2 is a gene sequencing pretreatment system structure schematic diagram in the embodiment of the present application;

[0020] Figure 3 is a quality control system structure schematic diagram in the embodiment of the present application;

[0021] Figure 4 is a library construction system structure schematic diagram in the embodiment of the present application;

[0022] Figure 5 is a structure schematic diagram of the synchronous buffering magnetic force plate of the embodiment of the present application;

[0023] Figure 6 is a cross-sectional view of the synchronous buffering magnetic force plate of the embodiment of the present application;

[0024] Figure 7 is a bottom connection structure schematic diagram of the synchronous buffering magnetic hole plate of the embodiment of the present application;

[0025] Figure 8 is a cross-sectional view of the synchronous buffering magnetic force plate and the bottom plate connection structure of the embodiment of the present application.

[0026] In the diagram: 10. Nucleic acid extraction system; 20. Library construction system; 21. PCR instrument; 22. Actual container for document construction; 23. Shaking and heating assembly; 24. Magnet assembly; 25. Working area of ​​the puncture assembly; 26. Waste container; 27. Large-capacity reagent container; 30. Quality control system; 31. Quantitative analyzer; 32. Quality control manipulator assembly; 33. Transfer mechanism; 34. Quality control pipetting assembly; 35. Construction reaction container; 36. Quality control container; 37. Detection reagent container; 40. Electrical control system; 50. Host computer; 101. Limiting block; 102. Magnet plate; 103. Magnetic ring; 201. Base; 202. Limiting screw; 203. Buffer spring; 301. Torsion bar; 302. Swing arm; 303. Connecting pin; 304. Top block; 305. Screw I; 306. Screw II. Detailed Implementation

[0027] To make the objectives, technical solutions, and advantages of this application clearer, the technical solutions of this application will be described in detail below. Obviously, the described embodiments are only a part of the embodiments of this application, and not all of them. Based on the embodiments in this application, all other implementation methods obtained by those skilled in the art without creative effort are within the scope of protection of this application.

[0028] It should be noted that when a component is referred to as "fixed to" or "set on" another component, it can be directly on the other component or may have an intervening component present. When a component is referred to as "connected to" another component, it can be directly connected to the other component or may have an intervening component present.

[0029] Figure 1 This is a schematic diagram of the nucleic acid extraction process. Figure 1 As shown in the embodiments of this application, nucleic acid extraction is a technique for separating nucleic acids from biological samples using 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.

[0030] For example, in the case of chemical separation, the nucleic acid molecules are released from the sample cells by lysing the sample cells with a cell lysis solution, and the nucleic acid molecules are present 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. For example, in the case of magnetic bead purification, magnetic beads are added to the lysate, and the nucleic acid molecules released from the sample cells are specifically adsorbed onto the surface of the magnetic beads, while the impurities such as proteins remain in the lysate. After a certain period of time, the magnetic beads to which the nucleic acid molecules are adsorbed are separated from the solution under the action of a magnetic field. The magnetic beads to which the nucleic acid molecules are adsorbed are then washed with a washing solution to wash away the impurities such as proteins. The washing is repeated several times to ensure that the nucleic acid molecules are washed clean. The magnetic beads to which the nucleic acid molecules are adsorbed are then recovered. Finally, the nucleic acid molecules are desorbed from the magnetic beads by elution with an elution solution. After a certain period of time, the magnetic beads are separated from the nucleic acid molecules under the action of a magnetic field. After the magnetic beads are removed, only pure nucleic acid molecules remain in the nucleic acid extraction product.

[0031] Further, the embodiments of the present application provide nucleic acid extraction product quality control. The concentration of nucleic acid molecules (such as DNA or RNA) in the nucleic acid extraction product solution needs to be detected (or quantitatively analyzed). The subsequent library construction process has certain requirements for the total amount of nucleic acid. If the actual amount of nucleic acid exceeds the total amount of nucleic acid required for the subsequent library construction process, the amplification efficiency during library construction will be affected. Therefore, the concentration of nucleic acid in the nucleic acid extraction product needs to be detected before library construction. After the concentration of nucleic acid is detected, the total volume of the nucleic acid extraction product required can be determined according to the concentration of nucleic acid and the total amount of nucleic acid required for the subsequent library construction process. When the detected concentration of nucleic acid is too high, the total volume of the nucleic acid extraction product required will be lower than the minimum volume of the pipetting device, which will affect the pipetting accuracy. Therefore, it is necessary to dilute the nucleic acid extraction product with a diluent (for example, pure water) before pipetting.

[0032] Further, the embodiments of the present application provide library construction. In the next-generation sequencing (NGS) technology, the nucleic acid molecules (such as DNA or RNA) extracted from biological samples need to be physically or enzymatically broken, for example, by ultrasonic waves. After being broken, the nucleic acid fragments are formed. The ends of the nucleic acid fragments are first filled with enzymes, and then the ends of the fragments are connected to specific DNA sequences (usually referred to as adaptors) by specific enzymes. Finally, the nucleic acid fragments are formed, which are referred to as libraries in the industry.

[0033] In order to save the cost of sequencing, generally, a plurality of biological samples are simultaneously sequenced in a sequencer, and in order to distinguish the sequencing results of different samples, a piece of DNA sequence (generally containing 6-8 bases) that can identify the sample source is contained in the adapter of the library of each sample when the library of each sample is prepared, and the piece of DNA sequence that can identify the sample source can also be referred to as a sample tag (or Index, Barcode). It can be understood that the library adapter of each sample contains a sample tag exclusive to the sample.

[0034] Further, the embodiment of the present application provides a library construction product quality control. The quality of the constructed library is crucial to the data quality of the subsequent gene sequencing output, and therefore, the quality of the library constructed by the library construction product needs to be detected and controlled before being sequenced. Generally, the library quality detection includes at least one of library length detection, library concentration detection and library contaminant detection. Among them, through the library concentration detection (or concentration quantitative analysis), the library concentration can be detected, and when the detected library concentration is too high, the total volume of the library construction product required for subsequent sequencing will be lower than the minimum liquid volume of the liquid handling device and affect the liquid handling precision, and therefore, it is necessary to add a diluent (for example, pure water) to the library construction product before liquid handling for moderate dilution. In addition, due to the difference between the library concentrations of a plurality of biological samples and the difference between the sequencing data outputs, the total volume of the library construction products of a plurality of biological samples required for subsequent sequencing will be different and ultimately affect the balance of the sequencing data outputs of a plurality of biological samples, and therefore, it is also necessary to add a diluent (for example, pure water) to the library construction product of part of the biological samples before liquid handling for dilution, so as to reduce the gap between the total volumes of the library construction products of a plurality of biological samples. Several common concentration detection methods include, for example, spectrophotometry, fluorescent dye detection method, microfluidic analysis method or capillary gel electrophoresis method.

[0035] Here, it should be noted that the concentration detection of the library construction product quality control and the nucleic acid extraction product quality control can adopt the same method or different methods, which is not limited in the present application.

[0036] Figure 2 is a structural schematic diagram of a gene sequencing pre-processing system in the embodiment of the present application. Further, the gene sequencing pre-processing system (or sequencing pre-processing instrument) provided by the embodiment of the present application comprises a nucleic acid extraction system 10, a library construction system 20, a quality control system 30, an electric control system 40 and an upper computer 50. Among them:

[0037] The nucleic acid extraction system 10 is configured to controllably release nucleic acid molecules (such as DNA or RNA) from biological samples;

[0038] The library construction system 20 is configured to controllably prepare nucleic acid molecules (such as DNA or RNA) into a library for sequencing by machine;

[0039] The quality control system 30 is configured to controllably detect the concentration of nucleic acid molecules in the nucleic acid extraction product and adjust the concentration of nucleic acid molecules to a pre-required concentration range according to the detection result, and / or 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;

[0040] The electric control system 40 is configured to control the operation and work of the nucleic acid extraction system 10, the library construction system 20, and the quality control system 30 according to the instructions of the host computer 50.

[0041] The host computer 50 is configured to control the operation and work of the nucleic acid extraction system 10, the library construction system 20, and the quality control system 30 by sending control instructions to the electric control system 40.

[0042] For the nucleic acid extraction system 10, taking the chemical method separation and the magnetic bead purification as an example, the nucleic acid extraction system 10 at least includes a nucleic acid extraction platform and a magnetic rod / magnetic rod sleeve assembly. The nucleic acid extraction platform is provided with an extraction operation container (such as a single reagent strip or a deep well plate) and a heating device (such as a heating block). The extraction operation container can contain biological samples and magnetic particles (such as magnetic beads) in addition to one or more reagents (such as cell lysis solution, washing solution, eluent) required for nucleic acid extraction, and provide reaction space for various chemical reactions (such as lysis reaction, washing reaction, elution reaction) in the nucleic acid extraction process; the heating device can provide suitable reaction temperature and reaction conditions for various chemical reactions occurring in the extraction operation container. The magnetic rod sleeve is sleeved on the magnetic rod to avoid the magnetic rod from being corroded by directly contacting the nucleic acid extraction reagent. When the magnetic rod / magnetic rod sleeve assembly enters the extraction operation container through the movement mechanism, it can provide the necessary magnetic field environment for the washing reaction and elution reaction in the nucleic acid extraction process.

[0043] It should be noted that the nucleic acid extraction system 10 can batch process multiple biological samples for nucleic acid extraction.

[0044] For the quality control system 30, as shown in Figure 3 , the quality control system 30 at least includes a quantitative analyzer 31, a quality control operation hand assembly 32 (only the working area thereof is shown in Figure 3 ), a conveying mechanism 33, a quality control pipetting assembly 34 (only the working area thereof is shown in Figure 3 ), a construction reaction container 35, a quality control container 36, and a detection reagent container 37. It should be noted that Figure 3 is only schematic and should not be understood as a limitation of the positions of the parts.

[0045] The nucleic acid extraction product and the library construction product can be contained in the construction reaction container 35 (e.g., a microplate), which further provides a reaction space for part of the chemical reactions in the library construction process. The detection container 36 (e.g., a centrifuge tube) can contain the detection substance and can be placed in the quantitative analyzer to realize detection. The detection reagent container 37 (e.g., a reagent kit) can contain one or more reagents required for concentration detection by the quantitative analyzer 31 and diluents for adjusting the concentration of the nucleic acid extraction product and the library construction product. The construction reaction container 35, the detection container 36, and the detection reagent container 37 are respectively located in their respective storage areas. The quality control operator assembly 32 and the quality control pipetting assembly 34 respectively work in their respective working areas. The storage area of the detection container 36 is located within the working area of the quality control operator assembly 32, and the storage areas of the construction reaction container 35 and the detection reagent container 37 are located within the working area of the quality control pipetting assembly 34. A transfer mechanism 33 is arranged between the working area of the quality control operator assembly 32 and the working area of the quality control pipetting assembly 34. The transfer mechanism 33 can reciprocally transfer the detection container 36 between the working area of the quality control operator assembly 32 and the working area of the quality control pipetting assembly 34.

[0046] Before the quality control starts, the quality control operator assembly 32 is responsible for taking the detection container 36 from the storage area of the detection container 36 and placing it on the transfer mechanism 33. The transfer mechanism 33 transfers the detection container 36 to the working area of the quality control pipetting assembly 34. The quality control pipetting assembly 34 is responsible for sucking a certain amount of detection reagent from the detection reagent container 37 and adding it to the detection container 36. The transfer mechanism 33 then transfers the detection container 36 (with the added detection reagent) back to the working area of the quality control operator assembly 32. The quality control operator assembly 32 is then responsible for placing the detection container 36 (with the added detection reagent) back in the storage area of the detection container 36.

[0047] In addition, if it is a nucleic acid extraction product quality control, the quality control pipetting assembly 34 also needs to be responsible for sucking the nucleic acid extraction product from the extraction operation container and adding it to the construction reaction container 35.

[0048] After the start of quality control, the quality control operator assembly 32 is responsible for taking the quality control container 36 (which has been added with the detection reagent) from the storage area of the quality control container 36 and placing it on the conveying mechanism 33, and the conveying mechanism 33 is responsible for conveying the quality control container 36 (which has been added with the detection reagent) to the working area of the quality control pipetting assembly 34, and the quality control pipetting assembly 34 is responsible for sucking a certain amount of nucleic acid extraction product / library construction product from the construction reaction container 35 and adding it to the quality control container 36, and stirring, and then the conveying mechanism 33 is responsible for conveying the quality control container 36 (which has been added with the detection reagent and the nucleic acid extraction product / library construction product) back to the working area of the quality control operator assembly 32, and the quality control operator assembly 32 is responsible for placing the quality control container 36 (which has been added with the detection reagent and the nucleic acid extraction product / library construction product) back to the storage area of the quality control container 36.

[0049] After the detection reagent and the nucleic acid extraction product / library construction product in the quality control container 36 react for a period of time, the quality control operator assembly 32 is responsible for taking the quality control container 36 from the storage area of the quality control container 36 and placing it into the quantitative analyzer 31 for concentration detection, and after the detection is completed, the quality control operator assembly 32 is responsible for taking the quality control container 36 and placing it back to the storage area.

[0050] If the detected concentration of nucleic acid molecules / library is higher than the required concentration, the quality control pipetting assembly 34 is also responsible for sucking a certain amount of pure water from the detection reagent container 37 and adding it to the construction reaction container 37 for dilution.

[0051] It should be noted here that the quality control system 30 can batch process the nucleic acid extraction product / library construction product of multiple biological samples. In the batch processing scenario, the quality control operator assembly 32 can take and place the quality control containers 36 one by one, or can take and place multiple quality control containers 36 at one time; correspondingly, the conveying mechanism 33 can convey the quality control containers 36 one by one, or can convey multiple quality control containers 36 at one time; the quality control pipetting assembly 34 can be a single-channel pipetting assembly, which sucks the detection reagent and adds it to the quality control container 36 one by one, or can be a multi-channel pipetting assembly, which sucks the detection reagent and adds it to multiple quality control containers 36 at one time, and the specific configuration can be freely set according to the occupied space and working efficiency. Figure 2 For example, in this example, the quality control operator assembly 32 takes and places the quality control containers 36 one by one, the conveying mechanism 33 is provided with two container positions and can reciprocate in opposite directions to convey each quality control container 36, and the quality control pipetting assembly 34 is a single-channel pipetting assembly.

[0052] In one implementation, the quality control pipetting assembly 34 can be a pipetting pump, which cooperates with the pipetting pump to perform pipetting. The pipetting pump is provided with a pipetting tip for pipetting. When pipetting starts, the pipetting pump sets the pipetting tip on the end of the pipetting pump. When pipetting is completed, the pipetting pump removes the pipetting tip from the end of the pipetting pump. Accordingly, the quality control system 30 is further provided with a tip storage area, as shown in Figure 3 .

[0053] For the library construction system 20, as shown in Figure 4 , the library construction system 20 at least includes a PCR instrument 21, a library construction operator assembly (only the working area thereof is shown in Figure 4 ), a library construction pipetting assembly (only the working area thereof is shown in Figure 4 ), library construction reagent containers 22, a shaking and heating assembly 23, and a magnet assembly 24. It should be noted that Figure 4 the above is only schematic and should not be construed as a limitation of the positions of the parts.

[0054] The library construction reagent containers 22 (e.g., reagent kits) can contain one or more reagents required for library construction. The library construction reagent containers 22, the shaking and heating assembly 23, and the magnet assembly 24 are respectively located in their respective storage areas, and the respective storage areas are located within the working area of the library construction operator assembly and the library construction pipetting assembly. The storage area of the library construction reagent containers 22 generally needs to be in a low-temperature refrigeration environment to facilitate low-temperature refrigeration of the library construction reagents. The shaking and heating assembly 23 is provided with a purification container (e.g., a deep-well plate) and a shaking and heating device. The purification container can provide a reaction space for magnetic bead purification in the library construction process. The shaking and heating device can provide suitable reaction temperature and reaction conditions for the magnetic bead purification. Meanwhile, the magnet assembly 24 can provide a necessary magnetic field environment for the magnetic bead purification.

[0055] After the nucleic acid extraction quality control is completed, the library construction operation hand assembly is responsible for taking the construction reaction container 35 (to which the nucleic acid extraction product has been added) from the quality control system 30 and placing it in a specific storage area in the library construction system 20, which can be referred to as a reagent addition area for convenience of description, since various reaction reagents are added to the construction reaction container 35, and since the nucleic acid is stored in the construction reaction container, the reagent addition area generally needs to be in a low-temperature refrigeration environment to facilitate low-temperature refrigeration of the nucleic acid. Since the entire library construction process includes multiple reaction steps, for each reaction step, the library construction pipetting assembly is first responsible for sucking the corresponding reaction reagent from the library construction reagent container 22 and adding it to the construction reaction container 35 (to which the nucleic acid extraction product has been added), and the library construction operation hand assembly is then responsible for placing the construction reaction container 35 (to which the nucleic acid extraction product and the corresponding reaction reagent have been added) into the PCR instrument 21 for reaction. After the reaction is complete, the library construction operation hand assembly takes the construction reaction container 35 from the PCR instrument 21 and places it back into the specific area in order to wait for the addition of the reaction reagent for the next reaction, and the above process is repeated.

[0056] In the library construction process, after the adapters are ligated to the ends of the nucleic acid fragments, the ligation products need to be purified to obtain a pure library. In addition, due to the small amount of library obtained at this time, library amplification is usually required, and after library amplification, the amplification products also need to be purified to obtain a pure library. If the magnetic bead method is used for purification, in addition to being able to accommodate one or more reagents required for library construction (including the washing solution and elution solution required for magnetic bead purification) in the library construction reagent container 22, magnetic beads or other magnetic particles can also be accommodated. During the magnetic bead purification reaction of the ligation product or the amplification product, the library construction pipetting assembly is responsible for first sucking the ligation product / amplification product from the construction reaction container 35 and adding it to the purification container of the shaking and heating assembly 23, then sucking the magnetic beads from the library construction reagent container 22 and adding them to the purification container (to which the ligation product / amplification product has been added), and after a certain period of reaction, the library construction operation hand assembly is responsible for transferring the purification container (in which the library is adsorbed on the surface of the magnetic beads) to the magnet assembly 24. Under the action of the magnetic field, the magnetic beads adsorbed with the library are separated from the solution, and the library construction pipetting assembly sucks the supernatant in the purification container to leave the magnetic beads adsorbed with the library. The library construction pipetting assembly continues to suck the washing solution from the library construction reagent container 22 and add it to the purification container, and after a certain period of reaction, the supernatant is sucked away. According to experimental needs, the library construction pipetting assembly can be repeatedly operated for multiple times of washing, and after washing is completed, the library construction operation hand assembly transfers the purification container to the shaking and heating assembly 23. The library construction pipetting assembly continues to suck the elution solution from the library construction reagent container 22 and add it to the purification container, and after a certain period of reaction, the library and the magnetic beads are desorbed. The library construction pipetting assembly then sucks the supernatant (i.e., the library construction product) in the purification container and adds it to the construction reaction container 35.

[0057] In general, a sealing film will be attached to the upper surface of the library construction reagent container 22 to facilitate the preservation and transportation of the internal reagents. After the reagent container is loaded into the inside of the pre-sequencing treatment instrument, the sealing film needs to be punctured by the puncturing assembly (only the working area thereof is shown) to facilitate the corresponding pipetting assembly to suck the reagents from the library file reagent container 22, and the storage area of the library construction reagent container 22 is located within the working area 25 of the puncturing assembly. Figure 4

[0058] In addition, considering that the volume of magnetic beads, washing solution, and elution solution 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 22, the library construction system 20 can further be provided with a large-capacity reagent container 27 for storing large-capacity reagents such as magnetic beads, washing solution, and elution solution.

[0059] ​It should be noted that the library construction operation hand assembly and the library construction pipetting assembly can be independently arranged. Considering that the library construction operation hand assembly and the library construction pipetting assembly do not need to work in parallel, the two assemblies can also be integrated for space saving. In addition, the library construction system 20 can perform library construction processing on nucleic acid extraction products of a plurality of biological samples in batches.

[0060] In an implementation manner, the library pipetting assembly can be a pipetting pump. In addition to the operation of the pipetting pump, a pipetting tip for pipetting is also needed. When the pipetting operation starts, the pipetting pump sets the pipetting tip on the end thereof. After the pipetting operation is completed, the pipetting pump separates the pipetting tip from the end thereof. Correspondingly, the library construction system 20 is also provided with a pipetting tip storage area. The used pipetting tip is put into the waste container 26, as shown in Figure 4 .

[0061] In the magnetic bead purification process, a magnet assembly commonly used, for example, includes a magnetic plate. In order to make the library construction pipetting assembly (for example, a multichannel pipetting pump) perform pipetting on the purification container (for example, a 96-deep-well plate) on the magnetic plate more uniformly and completely, a buffer synchronization structure magnetic plate is needed, which can ensure that the pipetting tip of the multichannel pipetting pump touches the bottom for pipetting, and at the same time, the magnetic force frame does not tilt, thereby ensuring the uniformity of pipetting.

[0062] To solve the technical problem, the present application provides a magnetic plate structure.

[0063] As shown in Figures 5 to 8 , the present application provides a synchronous buffer magnetic plate, which comprises a magnet hole plate 102, a base 201, a buffer mechanism and a synchronization mechanism. The magnet hole plate 102 is connected to the base 201 through the buffer mechanism and the synchronization mechanism. The buffer mechanism is a flexible support structure. The synchronization mechanism comprises a fixed end and a movable end. The fixed end is rotatably fixed on the base 201. The movable end is connected to both ends of the magnet hole plate 102 to drive the two ends of the magnet hole plate 102 to move synchronously.

[0064] Specifically, the magnet hole plate 102 provided with a magnetic ring 103 is supported by the buffer mechanism and the synchronization mechanism. The flexible support structure of the buffer mechanism provides a buffer when the magnet hole plate 102 is pressed. The movable end of the synchronization mechanism is connected to both ends of the magnet hole plate 102, so that the two ends of the magnet hole plate 102 move synchronously. Thus, the problem of tilting of the magnet hole plate 102 when it is stressed is solved, and the difference in pipetting effect caused by tilting is avoided.

[0065] As shown in Figure 8 , Figure 7As shown, as an optional implementation, the fixed end of the synchronization mechanism includes a torsion bar 301, with both ends of the torsion bar 301 rotatably mounted on the base 201; the movable end includes a swing arm 302, with two swing arms 302, one end of each swing arm 302 being fixedly connected to both ends of the torsion bar 301, and the end of the swing arm 302 away from the torsion bar 301 being connected to the magnet plate 102.

[0066] Specifically, the torsion bar 301 is rotatably mounted on the base 201, with its two ends connected to one end of each of the two swing arms 302. The other ends of the two swing arms 302 are connected to the two ends of the magnetic perforated plate 102 as movable ends. The movement of any end of the magnetic perforated plate 102 drives the swing arm 302 connected to it to move. The movement of the swing arm 302 drives the other swing arm 302 to move synchronously through the torsion bar 301, so as to realize the synchronous movement of both ends of the magnetic perforated plate 102.

[0067] like Figure 8 As shown, as an optional implementation, the end of the swing arm 302 away from the torsion bar 301 is provided with an elongated hole, the long side of which is set in the horizontal direction. A connecting pin 303 is provided on the magnet hole plate 102 corresponding to the elongated hole. The connecting pin 303 passes through the elongated hole to connect the swing arm 302 and the magnet hole plate 102.

[0068] Specifically, when one end is pressed, the pressed end of the magnet plate 102 sinks, and the connecting pin 303 in the pin hole sinks synchronously, causing the elongated hole of the swing arm 302 to sink. Simultaneously, the connecting pin 303 will move laterally within the elongated hole of the swing arm 302. Since the torsion bar 301 can only rotate, when the elongated hole of the swing arm 302 is pressed, the swing arm 302 will drive the torsion bar 301 to rotate. At the same time, the other end of the torsion bar 301 will drive the swing arm 302 at the other end to rotate, causing the elongated hole at the other end to move down, driving the connecting pin 303 at the other end to move down. The connecting pin 303 drives the other end of the magnet mounting plate to move down, thereby achieving synchronization at both ends.

[0069] like Figure 7 , Figure 8 As shown, in an optional embodiment, a mounting groove is provided on the base 201, and a torsion bar 301 is disposed in the mounting groove. The torsion bar 301 is cylindrical, and top blocks 304 are provided above both ends of the torsion bar 301. The top blocks 304 rotatably confine the torsion bar 301 within the mounting groove. The torsion bar 301 is located in the mounting groove of the base 201, and the top blocks 304 are fixed in the mounting groove by screws I305. The torsion bar 301 is restricted by the top blocks 304 and cannot move up and down, but it can rotate, thereby rotatably connecting to the base 201.

[0070] like Figure 8 Figure 8As shown, as an optional embodiment, four buffering mechanisms are provided, and the four buffering mechanisms are respectively supported at four corner ends of the magnet hole plate 102, and the movable end of the synchronous mechanism is connected at the middle position of the two end portions of the magnet hole plate 102.

[0071] Specifically, the four buffering mechanisms support the magnet hole plate 102 at the four corner ends of the magnet hole plate 102 in a flexible structure, and when the magnet hole plate 102 is pressed, the magnet hole plate 102 moves downward under the support of the buffering mechanisms, and the movable end of the synchronous mechanism is connected at the middle position of the two end portions of the magnet hole plate 102, so that when any one end of the magnet hole plate 102 moves downward, the other end can be driven to move downward synchronously through the synchronous mechanism, thereby realizing synchronous movement of the two ends of the magnet hole plate 102.

[0072] As an optional embodiment, the buffering mechanism includes a limiting screw 202 and a buffering spring 203, the buffering spring 203 supports the magnet hole plate 102 on the base 201, and the limiting screw 202 is fixed to the base 201 through the magnet hole plate 102 and the buffering spring 203, thereby limiting the highest position of the magnet hole plate 102. In a free state, the buffering spring 203 lifts the magnet mounting plate, so that the magnet mounting plate is separated from the base 201 and abuts against the limiting screw 202, and the limiting screw 202 limits the highest position of the magnet mounting plate separated from the base 201.

[0073] As an optional embodiment, the magnet hole plate 102 is further provided with a limiting block 101 located at the upper end of the limiting screw 202 and separated from the top surface of the limiting screw 202 by a certain distance, so as to limit the lowest position of the magnet hole plate 102. When the magnet hole plate 102 is pressed to move downward, the buffering spring 203 is compressed, and the limiting block 101 moves downward along the limiting screw 202 with the magnet hole plate 102, and stops at the top of the limiting screw 202 and no longer moves downward, thereby limiting the lowest position of the magnet hole plate 102.

[0074] As an optional embodiment, the top block 304 is fixed in the mounting groove, and the end surface of the top block 304 abutting against the torsion rod 301 is a bevel surface.

[0075] Specifically, the end surface of the top block 304 abutting against the torsion rod 301 is a bevel surface, and the bevel surface is arranged in the direction of the swing arm 302, so as to better balance the force on the torsion rod 301 from the swing arm 302.

[0076] As an optional embodiment, the two end portions of the torsion rod 301 are square, the torsion rod 301 is clamped into the corresponding hole of the swing arm 302 through the square end portions, and the torsion rod 301 is fixedly connected with the swing arm 302 through a screw.

[0077] Specifically, the two ends of the torsion bar 301 are quadrilateral structures, the middle is a cylindrical structure, the quadrilateral hole of the swing arm 302 is matched with the quadrilateral structure of the two ends of the torsion bar, and is fixed by the screw 306 II, so that the connection of the torsion bar 301 and the swing arm 302 is stable, and the connection end of the torsion bar 301 and the swing arm 302 rotates synchronously.

[0078] The application can realize the synchronization of the two ends of the magnetic plate through a simple structure, avoid the phenomenon of hole plate inclination during pipetting, has low cost and high reliability.

[0079] In the description of the present application, it should be noted that the terms "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer" and the like indicate the orientation or positional relationship shown in the drawings, and are only for the convenience of describing the present application and simplifying the description, and do not indicate or imply that the device or element referred to must have a particular orientation, be constructed and operated in a particular orientation, and therefore cannot be understood as a limitation on the present application. In addition, the terms "first", "second", "third" are only for the purpose of description, and cannot be understood as indicating or implying relative importance.

[0080] In the description of the present application, it should be noted that unless otherwise explicitly specified and limited, the terms "mounting", "connecting", "connecting" should be understood broadly, for example, it can be fixedly connected, or it can be detachably connected, or integrally connected; it can be mechanically connected, or it can be electrically connected; it can be directly connected, or it can be indirectly connected through an intermediate medium; it can be the communication inside two elements. For those skilled in the art, the specific meaning of the above terms in the present application can be understood according to the specific circumstances.

[0081] The above is only a specific embodiment of the present application, but the protection scope of the present application is not limited thereto, any person skilled in the art can easily think of changes or replacements within the technical range disclosed by the present application, which should be covered within the protection scope of the present application. Therefore, the protection scope of the present application should be subject to the protection scope of the claims.

Claims

1. A synchronous buffer magnetic plate, characterized by, It comprises: The magnet hole plate is connected with the base through the buffer mechanism and the synchronous mechanism, the buffer mechanism is a flexible support structure, the synchronous mechanism includes a fixed end and a movable end, the fixed end is rotatably fixed on the base, and the movable end is connected with both ends of the magnet hole plate to drive the synchronous movement of both ends of the magnet hole plate.

2. The synchronous buffer magnetic plate according to claim 1, wherein The fixed end of the synchronous mechanism includes a torsion bar, and the two ends of the torsion bar are rotatably arranged on the base; the movable end includes a swing arm, and the swing arm is provided in two, one end of each of the two swing arms is fixedly connected with the two ends of the torsion bar, and the other end of the swing arm away from the torsion bar is connected with the magnet hole plate.

3. The synchronous buffer magnetic plate of claim 2, wherein, The other end of the swing arm away from the torsion bar is provided with a long slot, the long side of the long slot is arranged along the horizontal direction, a connecting pin is arranged on the magnet hole plate corresponding to the long slot, and the connecting pin is arranged in the long slot to connect the swing arm and the magnet hole plate.

4. The synchronous buffer magnetic plate of claim 3, wherein, The base is provided with a mounting groove, the torsion bar is arranged in the mounting groove, the torsion bar is cylindrical, and the top block is arranged above the two ends of the torsion bar to rotatably limit the torsion bar in the mounting groove.

5. The synchronous buffer magnetic plate according to claim 4, wherein The buffer mechanism is provided with four, and the four buffer mechanisms are respectively supported at the four corner ends of the magnet hole plate, and the movable end of the synchronous mechanism is connected at the middle position of the two end portions of the magnet hole plate.

6. The synchronous buffer magnetic plate of claim 5, wherein, The buffer mechanism includes a limiting screw and a buffer spring, the buffer spring supports the magnet hole plate on the base, the limiting screw passes through the magnet hole plate and the buffer spring and is fixed to the base to limit the highest position of the magnet hole plate.

7. The synchronous buffer magnetic plate of claim 6, wherein, The magnet hole plate is also provided with a limiting block located at the upper end of the limiting screw and spaced apart from the top surface of the limiting screw by a certain distance to limit the lowest position of the magnet hole plate.

8. The synchronous buffer magnetic plate of claim 4, wherein, The top block is fixed in the mounting groove, and the end face of the top block pressing on the torsion bar is an inclined surface.

9. The synchronous buffer magnetic plate of claim 5, wherein, The two ends of the torsion bar are square, the torsion bar is clamped into the corresponding hole of the swing arm through the square end, and the torsion bar is fixedly connected with the swing arm through a screw.

10. A library construction system, characterized by, It comprises the synchronous buffer magnetic plate as claimed in any one of claims 1-9.

11. A system for pre-processing of genetic sequencing, characterized in that, It comprises the library construction system as claimed in claim 10.

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