Nucleic acid extractor and library preparation device

Abstract

The invention provides a nucleic acid extractor and a library preparation device.The nucleic acid extractor comprises a box internally provided with a cavity, and the box is defined by a bottom plate, side plates and a top plate; the nucleic acid extraction instrument further comprises a storage table, a magnetic bar sleeve assembly and a magnetic bar assembly, wherein the magnetic bar sleeve assembly and the magnetic bar assembly are arranged in the cavity. The side plates are provided with openings allowing the object placing table to penetrate through. The driving piece is arranged on the lower side of the bottom plate, and drives the object placing table to move between a taking and placing position and a reaction position in the first direction; a cabin door used for opening and closing the opening is arranged on the side plate, and the opening is closed when the object placing table is located at the taking and placing position or the reaction position. By adopting the technical scheme, the problem that aerosol and the like generated in the working process of the nucleic acid extraction instrument pollute other external areas can be relieved.

Description

Technical Field

[0001] The present application relates to the field of biotechnology, and in particular to a nucleic acid extraction instrument and a library preparation device. Background Art

[0002] Most of the existing nucleic acid extraction instruments are used alone. The staff places the sample in the corresponding position of the nucleic acid extraction instrument. After the extraction is completed, the extracted nucleic acid is collected and transferred to other equipment for subsequent steps, such as library preparation devices.

[0003] In this case, the staff needs to transfer the extracted nucleic acid, which is inconvenient. If the nucleic acid extractor is integrated into the library preparation device, the aerosol generated during the nucleic acid extraction of the sample will flow to other areas of the library preparation device, causing contamination and affecting the quality of library preparation. Summary of the invention

[0004] The present application provides a nucleic acid extractor and a library preparation device to alleviate the problem of aerosols generated during the working process of the nucleic acid extractor causing pollution to other external areas.

[0005] In a first aspect, the present application provides a nucleic acid extraction instrument, comprising a box body with a cavity formed inside, wherein the box body is composed of a bottom plate, a side plate and a top plate;

[0006] The nucleic acid extractor further comprises a storage table and a magnetic rod cover assembly and a magnetic rod assembly arranged in the cavity; wherein the storage table is used to carry the sample to be extracted and the reagents required for extraction, and the magnetic rod cover assembly and the magnetic rod assembly are used to carry the sample and transfer it between different extraction processes;

[0007] The side panel is provided with an opening for the storage table to pass through;

[0008] It also includes a driving member arranged at the lower side of the bottom plate, wherein a connecting hole is opened on the bottom plate along a first direction, and the driving member is connected to the storage platform through the connecting hole, and the storage platform is driven by the driving member to move between the pick-and-place position and the reaction position along the first direction;

[0009] The side panel is provided with a door for opening and closing the opening, and the opening is closed when the storage table is located at the pick-and-place position or the reaction position;

[0010] Wherein, the pick-and-place position is located outside the cavity, and the reaction position is located inside the cavity.

[0011] In a specific possible implementation manner, a sealing tape for sealing the communicating hole is provided on the bottom plate.

[0012] In a specific possible implementation manner, a rolling member is provided on a side of the storage platform facing the driving member, and the storage platform is connected to the driving member through the rolling member;

[0013] The sealing belt cooperates with the rolling member to seal the communicating hole.

[0014] In a specific possible implementation scheme, the rolling element includes a supporting block, a connecting block and a plurality of limiting rollers;

[0015] The support blocks are provided with two, and are used to be connected with the driving member and the storage table;

[0016] The connecting block and the limiting block are located between the two supporting blocks, and both ends of the connecting block and the limiting roller are connected to the supporting blocks;

[0017] The sealing belt spans over the connecting block, and the limiting rollers are distributed on both sides of the connecting block to limit the sealing belt to remain in cooperation with the rolling member to seal the communicating hole.

[0018] In a specific possible implementation scheme, the driving member includes a driving screw rotatably connected to the base plate, a sliding block sleeved on the driving screw, a driving motor whose output end is connected to the driving screw, and a frame fixedly connected to the lower side of the base plate; the driving screw and the driving motor are connected to the frame;

[0019] The sliding block is threadedly matched with the driving screw and is fixedly connected to the storage table. In a specific implementation scheme, it also includes a support bracket and a plurality of consumables;

[0020] Wherein, the support frame is carried on the storage table;

[0021] A plurality of the consumables are arranged on the support frame along a first direction and are detachably connected to the support frame;

[0022] Each of the consumables is provided with a plurality of consumable holes along the second direction, and the plurality of consumable holes are respectively used to store samples to be extracted and reagents required for extraction;

[0023] The first direction is perpendicular to the second direction.

[0024] In a specific possible implementation scheme, a mounting frame is fixedly connected to the bottom plate, and a displacement component is provided on the mounting frame;

[0025] The shift assembly comprises a shift plate slidably connected to the mounting frame along the second direction and a shift driving member arranged on the mounting frame, wherein the shift driving member is connected to the shift plate to drive the shift plate to slide;

[0026] The magnetic rod sleeve assembly and the magnetic rod assembly are both arranged on the shift plate;

[0027] The first direction is perpendicular to the second direction.

[0028] In a specific possible implementation scheme, the magnetic rod sleeve assembly includes a magnetic rod sleeve frame and a plurality of magnetic rod sleeves arranged on the magnetic rod sleeve frame, and the magnetic rod sleeve frame is slidably connected to the shift plate along the third direction;

[0029] The shift plate is also provided with a lifting drive member for driving the magnetic rod sleeve to slide relative to the shift plate;

[0030] The magnetic rod assembly comprises a magnetic rod frame and a plurality of magnetic rods arranged on the magnetic rod frame, and the magnetic rod frame is slidably connected with the magnetic rod sleeve frame along a third direction;

[0031] The magnetic rod frame is provided with a secondary driving member for driving the magnetic rod frame to slide relative to the magnetic rod sleeve frame;

[0032] Wherein, the third direction is perpendicular to the bottom plate, and the plurality of magnetic rods correspond to the plurality of magnetic rod sleeves one by one.

[0033] In a specific possible implementation scheme, the secondary driving member includes a screw rod threadedly matched with the magnetic rod sleeve and a motor fixed relative to the magnetic rod frame, and the motor is used to drive the screw rod to rotate;

[0034] The screw rod passes through the magnetic rod frame and is rotationally connected to the magnetic rod frame, and the magnetic rod frame and the screw rod are relatively fixed in the third direction.

[0035] In a specific possible implementation scheme, it also includes a controller, a photoelectric sensor and a warning element;

[0036] Wherein, a photoelectric sensor is arranged in the box body and is used to detect the position of the magnetic rod sleeve relative to the magnetic rod sleeve frame;

[0037] The controller is signal-connected to the photoelectric sensor and the warning element, and is used to trigger the warning element to send an alarm signal when the photoelectric sensor detects that the magnetic rod sleeve is offset relative to the magnetic rod sleeve frame.

[0038] In a specific possible implementation scheme, a pressing piece is detachably connected to the support bracket;

[0039] The pressing member cooperates with the supporting bracket to clamp the consumable material to limit the position of the consumable material.

[0040] In a specific possible implementation manner, the consumable is provided with an identification mark for identifying the sample on the consumable.

[0041] In a specific implementation manner, the identification mark is an identification code for scanning by an identification device.

[0042] In a specific implementation manner, a plurality of ultraviolet lamps are provided in the box.

[0043] In a specific implementation scheme, the nucleic acid extractor further includes a ventilation module, and the ventilation module includes an air inlet, an air outlet, and a fan arranged on the box body;

[0044] The air inlet and the air outlet are located at two locations on the box body that are far away from each other;

[0045] The internal space of the box body is connected to the outside through the air inlet and the air outlet;

[0046] The fan is located at the air outlet to form an air flow from the air inlet to the air outlet and flows through the experimental area in the box.

[0047] In a specific possible implementation manner, the ventilation module further includes a filter disposed at the air outlet for filtering the airflow.

[0048] In a second aspect, the present application also provides a library preparation device, comprising a nucleic acid extraction instrument as described in any one of the above items. BRIEF DESCRIPTION OF THE DRAWINGS

[0049] Figure 1 A schematic diagram of the overall structure of a nucleic acid extraction instrument provided in an embodiment of the present application;

[0050] Figure 2 A schematic diagram of a magnetic rod sleeve assembly and a magnetic rod assembly of a nucleic acid extractor provided in an embodiment of the present application;

[0051] Figure 3 A schematic diagram of the matching relationship between the sealing belt and the rolling member provided in the embodiment of the present application;

[0052] Figure 4 A schematic diagram of the structure of a driving member and a rolling member provided in an embodiment of the present application;

[0053] Figure 5 A schematic diagram of the structure of the support frame and consumables provided in the embodiment of the present application;

[0054] Figure 6 A schematic diagram of the structure of a displacement assembly driving a magnetic rod sleeve and a magnetic rod provided in an embodiment of the present application;

[0055] Figure 7 A schematic diagram of the working principle of the photoelectric sensor provided in the embodiment of the present application;

[0056] Figure 8A perspective schematic diagram showing a ventilation module provided in an embodiment of the present application. DETAILED DESCRIPTION

[0057] 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.

[0058] 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.

[0059] To facilitate understanding of the nucleic acid extractor provided in the embodiment of the present application, its application scenario is first explained. The nucleic acid extractor provided in the embodiment of the present application is used for the extraction of nucleic acids. Most of the existing nucleic acid extractors are used alone. The staff places the sample in the corresponding position in the nucleic acid extractor. After the extraction is completed, the nucleic acid obtained in the extraction is collected and transferred to other equipment for subsequent other steps, such as a library preparation device. In this case, the staff is required to transfer the extracted nucleic acid, which is inconvenient; if the nucleic acid extractor is integrated into the library preparation device, the aerosol generated during the nucleic acid extraction of the sample will flow to other areas of the library preparation device, causing pollution and affecting the quality of library preparation. To this end, the embodiment of the present application provides a nucleic acid extractor, a library preparation device and a nucleic acid extraction process to overcome the current problem of waste of resources. The following is a detailed description of it in conjunction with specific drawings and embodiments.

[0060] First reference Figure 1 and Figure 2, which shows the main structural schematic diagram of the nucleic acid extractor, which is used to extract nucleic acid from samples to obtain target nucleic acid. The nucleic acid extractor includes a box 1 with a cavity formed inside, and the box 1 is composed of a bottom plate 11 and a side plate and a top plate, and one of the side plates is provided with an opening and a hatch 12 for opening and closing the opening to achieve the operation of taking and placing samples, reagents and other items; the bottom plate 11 is provided with a storage table 2, a magnetic rod sleeve assembly 3 and a magnetic rod assembly 4. Among them, the storage table 2 is used to carry the sample to be extracted, and the magnetic rod sleeve assembly 3 and the magnetic rod assembly 4 are used to carry the sample between different extraction processes through magnetic beads.

[0061] refer to Figure 1 and Figure 2 , the placing table 2 is slidably connected to the bottom plate 11 along a first direction, and can stop at a corresponding position relative to the bottom plate 11; in addition, the nucleic acid extractor also includes a driving member 21 disposed on the lower side of the bottom plate 11 for driving the placing table 2 to move, and the driving member 21 drives the placing table 2 to pass through the opening on the box body 1 and slide in the direction of the inside and outside of the box body 1. When placing the sample on the placing table 2, and when the extraction work is completed and the target nucleic acid is taken away, the placing table 2 is located outside the box body 1, which reduces the influence of factors such as narrow space, and makes the taking and placing operation more convenient.

[0062] A connecting hole extending in the first direction is provided on the bottom plate 11, the storage table 2 is located on the upper side of the bottom plate 11, the driving member 21 is located on the lower side of the bottom plate 11, and the driving end of the driving member 21 is connected to the storage table 2 through the connecting hole to drive the storage table 2, and drive the storage table 2 to move between the pick-and-place position and the reaction position in the first direction. The pick-and-place position is located outside the cavity of the box body 1, and the objects on the storage table 2 are picked up and placed; the reaction position is located inside the cavity of the box body 1, and the sample is extracted.

[0063] For example, reference Figure 3 and Figure 4 The driving member 21 is a screw slider structure, including a driving motor 211, a driving screw 212 and a sliding block 213. The driving screw 212 extends along the first direction and is rotatably connected to the lower side of the base plate 11. A threaded hole for the driving screw 212 to pass through is provided on the sliding block 213. The driving screw 212 is inserted into the threaded hole, and the two are threadedly matched. In addition, the sliding block 213 passes through the connecting hole and is fixedly connected to the storage table 2; the driving motor 211 is fixedly connected relative to the base plate 11, and the driving motor 211 is connected to the driving screw 212 to drive the driving screw 212 to rotate.

[0064] The bottom side of the bottom plate 11 is fixedly connected with a frame 111, a driving motor 211 is fixedly connected in the frame 111, and a driving lead screw 212 is rotatably connected to the frame 111. In addition, a limit block 112 is also provided in the frame 111, the limit block 112 is attached to the inner side wall of the frame 111, and a sliding block 213 is fixedly connected to the limit block 112, which can improve the stability of the sliding block 213 sliding under the driving lead screw 212.

[0065] In this way, the position of the storage table 2 can be adjusted more conveniently by setting the driving member 21, and the driving member 21 is set at the lower side of the bottom plate 11, which reduces the occupation of the internal space of the box body 1 and improves the internal space utilization.

[0066] In addition, in the nucleic acid extractor, the drive member 21 is arranged on the lower side of the bottom plate 11, which will not occupy the space of the internal cavity of the box 1, and when the drive member 21 drives the storage table 2 to move to the pick-up position or the reaction position, the hatch 12 can be used to close the opening on the box 1, so as to keep the internal cavity of the box 1 isolated from the external environment, reduce the diffusion of aerosols generated by the reaction process into the surrounding environment, and reduce the pollution problems caused to the surrounding environment. In this way, when the nucleic acid extractor is integrated into the library preparation device, it is not easy to cause pollution to other areas, which is conducive to improving the quality of library preparation and reducing the problem that the nucleic acid extractor and the library preparation device cannot be integrated due to pollution problems.

[0067] In order to ensure that the cavity in the box body 1 has better sealing performance, a sealing belt 13 for sealing the communication hole is provided on the bottom plate 11.

[0068] By setting the sealing belt 13, a good sealing effect is maintained inside the box 1, and the connecting hole prevents the box 1 from always being connected to the outside, which makes the space inside the box 1 easily contaminated, avoids the contamination of the finally extracted nucleic acid, and achieves a better extraction effect.

[0069] Specifically, a rolling member 22 is provided on the side of the storage table 2 facing the driving member 21, and the storage table 2 is connected to the driving member 21 through the rolling member 22; and the sealing belt 13 cooperates with the rolling member 22 to seal the connecting hole, thereby improving the sealing of the box body 1 and further reducing the problem of pollution caused by the aerosol spreading outward.

[0070] refer to Figure 4The rolling element 22 includes a support block 221, a connection block 222 and a limiting roller 223, wherein two support blocks 221 are provided and fixedly connected to the storage platform 2, the connection block 222 and the limiting roller 223 are located between the two support blocks 222, and both ends of the connection block 222 and the limiting roller 223 are connected to the two support blocks 222, so that the rolling element 22 forms a whole, and a gap is left between the connection block 222, the limiting roller 223 and the storage platform 2. The sealing belt 13 crosses the connection block 222, and the position of the sealing belt 13 is limited by the limiting roller 223, so that the sealing belt 13 cooperates with the rolling element 22 to seal the communication hole.

[0071] Exemplarily, there are two limiting rollers 223, which are rotatably connected to the support block 221, and the two limiting rollers 223 are respectively located on both sides of the connection block 222 in the extension direction of the sealing belt 12; the sealing belt 13 extends from the lower side of one limiting roller 223 to the upper side of the connection block 222, and passes through the lower side of the other limiting roller 223. The limiting roller 223 limits the sealing belt 13, which can ensure that the sealing belt 13 has a relatively stable sealing performance on the connecting hole.

[0072] In addition, an arc transition is provided on the edge of the connecting block 222 that is connected to the sealing belt 13. The sealing belt 13 crosses the connecting block 222 and remains in contact with the arc surface on the upper side of the connecting block 222. In this way, in the process of driving the storage table 2 to slide, the sealing belt 13 slides more smoothly relative to the connecting block 222, reducing the wear on the sealing belt 13.

[0073] The rolling piece 22 is provided to achieve stable positioning of the sealing belt 13. During the sliding process of the storage table 2, the sealing belt 13 and the rolling piece 22 are always kept in cooperation with each other to seal the connecting hole, and the overall sealing effect of the box body 1 is better.

[0074] refer to Figure 1 The bottom plate 11 has an extension section 14 on one side of the opening facing away from the cavity in the box body 1, so that the storage table 2 can slide to the outside of the box body 1. When the storage table 2 slides onto the extension section 14, it is in the pick-up and place position.

[0075] In this way, in addition to closing the hatch 12 when performing nucleic acid extraction, so that the space inside the box 1 remains isolated from the outside world and avoids contamination of the outside world during nucleic acid extraction; before the extraction operation and after the extraction is completed, the storage table 2 slides onto the extension section 14, and the hatch 12 can be closed. Then, the samples, nucleic acids, etc. placed on the storage table 2 can be taken and placed, thereby reducing the contamination of the external environment, reagents, etc. caused by the reagents in the nucleic acid extractor.

[0076] refer to Figure 1The hatch 12 is sealed with the box 1, and an opening and closing drive 15 is provided between the box 1 and the hatch 12, which is used to drive the hatch 12 to move relative to the box 1 to open and close the opening of the box 1. The opening and closing drive 15 can be a linear drive structure such as a cylinder, a hydraulic cylinder, an electric push rod, or a transmission structure such as a screw slider, a gear rack, a chain, a worm gear, etc.; Figure 1 Only a partial structure of the opening and closing drive member 15 is shown. When actually set, it can be designed according to the existing structure in the relevant field, and it only needs to be able to open and close the cabin door 12.

[0077] The automation level of the nucleic acid extractor is further improved, and the use is more convenient. In addition, through this setting, it is convenient to integrate the nucleic acid extractor with other equipment.

[0078] Exemplarily, the nucleic acid extractor is integrated into other nucleic acid detection experimental equipment. During the process, the staff only needs to manually place the sample on the corresponding consumables 6. After that, the staff does not need to manually operate. The storage table 2 can be automatically moved to the corresponding position inside the box 1, and the hatch 12 is closed to perform the extraction operation; after the extraction is completed, the hatch 12 automatically opens, and the storage table 2 is moved outside the box 1, and then the extracted target nucleic acid is transferred to the subsequent detection process by setting a mechanical arm. In the above process, except for the staff who need to place the sample, the remaining process can be completed automatically, which greatly improves the convenience of use. In addition, since the intermediate process does not require manual operation by the staff, the corresponding steps can always be completed in an environment isolated from the outside world, further reducing the risk of contamination of samples, target nucleic acids, etc. during the process, and the extraction effect is better.

[0079] refer to Figure 5 The nucleic acid extraction instrument also includes a support frame 5 and a plurality of consumables 6, and the support frame 5 is carried on the storage table 2; illustratively, the support frame 5 can be directly placed on the storage table 2, or the position of the support frame 5 relative to the storage table 2 can be limited by structures such as buckles, slots, and limit plates.

[0080] The support frame 5 is provided with placement holes for accommodating the consumables 6. When actually set, the number of placement holes set on the support frame 5 can be adjusted according to actual needs; Figure 5 The support frame 5 is provided with four placement holes, each of which accommodates a group (plurality) of consumables 6.

[0081] Among them, the main part of the consumable material 6 is located in the placement hole, and the two ends of the consumable material 6 that are far away from each other are integrally formed with overlapping edges, which are overlapped on the supporting frame 5. Specifically, the overlapping edges overlap the edge part of the placement hole.

[0082] In one embodiment, a clamping member 51 is detachably connected to the support frame 5, and the clamping member cooperates with the support frame to clamp the overlapping edge of the consumable 6 to limit the position of the consumable; the clamping member 51 and the support frame 5 can be connected by means of snaps, magnets, etc. In actual use, the consumable 6 may be pasted with a sealing film for sealing each consumable hole 61, and the position of the consumable 6 relative to the support frame 5 is limited by the provided clamping member 51, so that when the sealing film on the consumable 6 is torn off, the consumable 6 is prevented from lifting from the support frame 5, and the operation is more convenient; it can also avoid problems such as the consumable 6 lifting and then falling, causing the internal sample to splash out.

[0083] Exemplarily, a limiting portion is provided on the inner side surface of the placement hole, and the position of each consumable is determined by the limiting portion, which can ensure the accuracy of the position of the consumable 6 relative to the support frame 5 and avoid position deviation that interferes with the subsequent extraction process.

[0084] A plurality of consumable holes 61 are provided on the consumable 6 along the second direction, respectively used to store samples to be extracted and various reagents required for extraction. Exemplarily, the plurality of consumable holes 61 are divided into a sample slot, a magnetic bead slot, a lysis slot, a rinse slot, and an elution slot, wherein the number of rinse slots can be set as needed to perform multiple rinse processes during the extraction process, which is beneficial to improving the purity of the target nucleic acid obtained by elution.

[0085] For the convenience of subsequent description, the following explanation is made: the first direction is the moving direction when the object is placed into the box 1 or taken out of the box 1 through the opening on the box 1, which is located in the horizontal plane; the second direction is also located in the horizontal plane and is perpendicular to the first direction. In addition, a third direction is set, which is perpendicular to the plane where the first direction and the second direction are located, that is, the up and down direction of the nucleic acid extraction instrument reagent in the use state.

[0086] During actual use, according to the number of samples to be extracted, the corresponding number of consumables 6 is installed on the support frame 5, and samples, magnetic beads or various corresponding reagents are placed in different consumable holes 61. Then, the support frame 5 equipped with consumables 6 is placed on the storage table 2, and then the subsequent extraction process is carried out. It can be seen that when the nucleic acid extractor is used for nucleic acid extraction, the corresponding number of consumables 6 can be used according to the number of samples to be extracted, and there is no limitation that only 16 copies (or 8 copies or other specified numbers) of samples can be extracted at one time. It can be more conveniently applied to the extraction operation of different numbers of samples such as one copy, two copies, and three copies. In addition, when extracting different numbers of samples, there is no contamination of reagents in other holes corresponding to where samples should be placed for extraction operations, which reduces the problem of reagent waste.

[0087] The consumable 6 is provided with an identification mark for identifying the sample on the corresponding consumable 6. In actual use, the identification mark is provided to facilitate the distinction between different samples. Exemplarily, the identification mark is an identification code for scanning by an identification device, such as a barcode, a QR code, etc. When performing nucleic acid extraction, scanning the identification code on the consumable 6 can conveniently distinguish different consumables 6 (samples).

[0088] In addition, a number of ultraviolet lamps are provided in the box 1, which can disinfect the space in the box 1 before and after the experiment to prevent contamination, improve the purity of the extracted nucleic acid, and reduce the risk of low experimental accuracy due to contamination.

[0089] refer to Figure 6 , a mounting frame 16 is fixedly connected to the bottom plate 11 inside the box body 1, and a shift assembly 7 is arranged on the mounting frame 16. The magnetic rod sleeve assembly 3 and the magnetic rod assembly 4 are both mounted on the shift assembly 7, and the magnetic rod sleeve assembly 3 and the magnetic rod assembly 4 are driven to move in the second direction by the shift assembly 7. The shift assembly 7 includes a shift plate 71 slidably connected to the mounting frame 16 along the second direction and a shift drive member 72 fixedly connected to the mounting frame 16, and the shift drive member 72 is connected to the shift plate 71 to drive the shift plate 71 to slide in the second direction; the magnetic rod sleeve assembly 3 and the magnetic rod assembly 4 are both arranged on the shift plate 71. Exemplarily, the shift drive member 72 is a lead screw slider structure, and can refer to the way in which the drive member 21 drives the storage table 2 to move, so as to drive the shift plate 71 to slide relative to the mounting frame 16, and its structure is not described in detail here.

[0090] The shifting assembly 7 drives the magnetic rod sleeve assembly 3 and the magnetic rod assembly 4 to move in the second direction so as to correspond to different consumable holes 61 on the consumable 6 , thereby driving the transfer of magnetic beads between different consumable holes 61 .

[0091] refer to Figure 6 The magnetic rod sleeve assembly 3 includes a magnetic rod sleeve frame 31 and a plurality of magnetic rod sleeves 32 installed on the magnetic rod sleeve frame 31. The installation here refers to the detachable fixed connection between the magnetic rod sleeve 32 and the magnetic rod sleeve frame 31; wherein the magnetic rod sleeve frame 31 is slidably connected to the shift plate 71 along the third direction, and a lifting drive member 74 is fixedly connected to the shift plate, and the lifting drive member 74 is connected to the magnetic rod sleeve frame 31 to drive the magnetic rod sleeve frame 31 to slide relative to the shift plate 71.

[0092] Exemplarily, the lifting drive 74 includes a lifting plate that is slidably connected to the shift plate 71 along the third direction, and the magnetic rod sleeve assembly 3 is fixed on the lifting plate; the lifting drive 74 drives the lifting plate to slide by means of belt transmission. Specifically, the lifting drive 74 also includes two pulleys that are rotatably connected to the shift plate 71, a belt that is tensioned on the two pulleys, and a motor that is fixedly connected to the shift plate 71. The lifting plate is fixedly connected to one side of the belt, and the motor drives the belt to rotate, driving the lifting plate to slide and lift along the third direction. In actual use, in order to ensure the stability of driving the magnetic rod sleeve 31 to slide, the belt is set as a synchronous belt, that is, the inner side of the belt and the pulley are provided with toothed structures that cooperate with each other.

[0093] The magnetic rod assembly 4 includes a magnetic rod frame 41, a plurality of magnetic rods 42 mounted on the magnetic rod frame 41, and a secondary driving component 43 arranged on the lifting plate, wherein the secondary driving component 43 is used to keep the magnetic rod frame 41 stationary relative to the lifting plate and the magnetic rod sleeve frame 31, or to drive the magnetic rod frame 41 and the magnetic rods 42 to slide relative to the lifting plate and the magnetic rod sleeve 32; wherein the magnetic rod sleeve 32 is used to extend into different placement holes, and the plurality of magnetic rods 42 correspond to the plurality of magnetic rod sleeves 32 one by one.

[0094] The secondary drive member 43 includes a screw threadedly matched with the magnetic rod sleeve 31 and a motor fixedly connected to the lifting plate, and the motor is used to drive the screw to rotate; the screw passes through the magnetic rod frame 41, is rotationally connected to the magnetic rod frame 41, and the magnetic rod frame 41 and the screw are relatively fixed in the third direction. Here, the magnetic rod frame 41 and the screw are relatively fixed in the third direction, which means that the two only rotate relative to each other, but do not slide relative to each other in the third direction. In this way, the motor drives the screw to rotate, driving the magnetic rod frame 41 to slide relative to the magnetic rod sleeve 31 in the third direction, thereby completing the adjustment of the relative position of the magnetic rod 42 and the magnetic rod sleeve 32.

[0095] When nucleic acid extraction is performed, it specifically includes processes such as mixing and magnetic adsorption. In the mixing stage, the magnetic rod cover 32 needs to move alone to mix the nucleic acid and magnetic beads. In the magnetic adsorption stage, the magnetic rod 42 is inserted into the magnetic rod cover 32 to keep the combination of magnetic beads and nucleic acid adsorbed on the surface of the magnetic rod cover 32. The magnetic rod cover 32 and the magnetic rod 42 move synchronously to transfer the combination of magnetic beads and nucleic acid to the subsequent washing and elution holes to complete the corresponding washing and elution process. That is, in the above-mentioned mixing stage, the magnetic rod cover 32 moves alone, and in the magnetic adsorption stage, the magnetic rod cover 32 and the magnetic rod 42 move synchronously.

[0096] Through the technical solution provided in the present application, in the mixing stage, the magnetic rod sleeve 32 is driven to move by the lifting drive 74. In the magnetic adsorption stage, the magnetic rod 42 is first driven by the secondary drive 43 to be inserted into the magnetic rod sleeve 32, and the magnetic rod 42 is kept stationary relative to the magnetic rod sleeve 32, so that the combination of magnetic beads and nucleic acids is adsorbed on the surface of the magnetic rod sleeve 32; subsequently, the lifting drive 74 drives the magnetic rod sleeve 32 and the magnetic rod 42 to move synchronously, carrying the combination of magnetic beads and nucleic acids for subsequent washing and elution.

[0097] It can be seen that in the technical solution of the present application, during the magnetic adsorption stage, the combination of magnetic beads and nucleic acids is kept adsorbed on the surface of the magnetic rod sleeve 32, and the magnetic rod sleeve 32 and the magnetic rod 42 are driven to move synchronously by the lifting drive member 74. Compared with the method of driving the magnetic rod sleeve 32 and the magnetic rod 42 to move separately through a separate driving structure, the difficulty of operation is reduced, and the problem of equipment damage or unstable adsorption caused by the asynchronous movement of the magnetic rod sleeve 32 and the magnetic rod 42 is avoided.

[0098] It should be noted that the specific structures of the driving member 21, the shifting driving member 72, the lifting driving member 74 and the secondary driving member 43 in the present application are only illustrative descriptions in the above descriptions. In actual use, different driving structures can be set and selected as needed, as long as the corresponding driving functions can be stably realized. The purpose is to achieve the required functions.

[0099] refer to Figure 7 The nucleic acid extraction instrument also includes a controller 8, a photoelectric sensor 81 and a warning element 82, wherein the photoelectric sensor 81 is fixedly connected to the box body 1 and can be selectively installed on the cabin door 12 or the inner wall of the box body 1, and is used to detect the relative position of the magnetic rod sleeve 32 relative to the magnetic rod sleeve frame 31; the controller 8 is signal-connected to the photoelectric sensor 81 and the warning element 82, and is used to trigger the warning element 82 to send an alarm signal when the photoelectric sensor 81 detects that the magnetic rod sleeve 32 is offset relative to the magnetic rod sleeve frame 31.

[0100] A plurality of magnetic rod sleeves 32 are grouped together and inserted into the magnetic rod sleeve frame 31. The position of the magnetic rod sleeve 32 is detected by the photoelectric sensor 81 to determine whether it is inserted in place. When it is detected that the magnetic rod sleeve 32 is not inserted into the specified position, the controller 8 triggers the warning element 82 to send an alarm signal, and the staff adjusts the position of the magnetic rod sleeve 32. This avoids the problem of collision between the magnetic rod sleeve 32 and the consumable 6, and collision between the magnetic rod 42 and the magnetic rod sleeve 32 when nucleic acid extraction is performed without being inserted into the specified position.

[0101] Among them, the warning element 82 can be a warning light, a buzzer, a display screen and other elements to prompt the staff when the alarm signal is triggered; when the alarm element is a display screen, the installation position of the magnetic rod sleeve 32 can also be displayed in real time on the display screen. If there is a position deviation when the magnetic rod sleeve 32 is installed for the first time, it can be corrected in one go, which is more convenient.

[0102] In addition, in actual settings, the controller 8 is also connected to the drive member 21, the shift drive member 72, the lifting drive member 74, and the secondary drive member 43 by signal. Of course, other sensors can also be set to be connected to the controller 8 by signal. The controller 8 controls the actions of each component according to the set program or the information detected by the sensor. This part is an existing design in the relevant field, and those skilled in the art can selectively set it according to actual needs. This part will not be repeated in the embodiments of this application.

[0103] refer to Figure 8 The nucleic acid extractor is also provided with a ventilation module 9, through which an air duct of the experimental area for the extraction process is formed in the box 1. Specifically, the ventilation module 9 includes an air inlet 91 and an air outlet 92, through which the internal and external spaces of the box 1 are connected; a fan 93 is provided at the air outlet 92 to drive the gas flow, forming an airflow from the air inlet 91 to the air outlet 92, and flowing through the experimental area inside the box 1; the air inlet 91 and the air outlet 92 are located at two places on the box 1 that are far away from each other, and the height of the air inlet 91 is lower than the height of the air outlet 92.

[0104] Exemplarily, the air inlet 91 is located at the lower side of one of the side walls of the box body 1 adjacent to the side where the opening is located, the air outlet 92 is located at the upper side of the side wall of the box body 1 opposite to the opening, and the air outlet 92 is located on the side away from the side wall where the air inlet 91 is located.

[0105] The air duct formed above drives the gas flow in the box 1, avoiding the gas volatilized during the experiment from generating eddy currents inside the box 1 and causing gas aerosol contamination, which is beneficial to improving the purity of the extracted nucleic acid and improving the extraction quality.

[0106] In addition, a filter is provided at the air outlet 92 to filter the airflow in the box 1 to avoid pollution to the outside.

[0107] In actual configuration, the air outlet 92 can also be set to two, and the fan 93 and the filter are also set corresponding to the air outlet 92; for example, the two air outlets 92 are located on the side wall of the box body 1 away from the opening, and are arranged in the direction close to and away from the side wall where the air inlet 91 is located. Alternatively, the air outlet 92 can also be set on the side wall away from the side wall where the air outlet 91 is located.

[0108] The present application also provides a library preparation device, which includes the above-mentioned nucleic acid extractor, and the nucleic acid extractor is integrated into the library preparation device. Compared with the prior art, the independent setting of the nucleic acid extractor improves the convenience of use and reduces the risk of contamination.

[0109] The present application also provides a nucleic acid extraction method, which is implemented based on the above-mentioned nucleic acid extraction instrument and mainly includes the following steps.

[0110] The hatch 12 is opened, and the drive member 21 drives the storage platform 2 to slide from the reaction position inside the box body 1 to the pick-up and place position outside the box body 1;

[0111] Close the hatch 12;

[0112] Place the sample to be extracted on the storage table 2, open the door 12, and the driving member 21 drives the storage table 2 loaded with the sample to slide to the reaction position;

[0113] Close the hatch 12;

[0114] After the reaction is completed, the door 12 is opened, the driving member 21 drives the storage table 2 loaded with the extracted nucleic acid to slide to the loading and unloading position, and the door 12 is closed.

[0115] Among them, placing the samples to be extracted on the storage table 2 specifically includes the following steps: determining the number of samples to be extracted, installing a corresponding number of consumables 6 on the support frame 5 according to the number of samples to be extracted, and placing the samples and reagents required for extraction in each consumable hole 61 of the consumable 6. The magnetic beads required in the process of extracting nucleic acid can be placed in one of the consumable holes 61, or a structure for placing magnetic beads can be set up to store the magnetic beads. In the embodiment of the present application, placing the magnetic beads in one of the consumable holes 61 is used as an example for explanation.

[0116] At this time, the storage table 2 is located inside the box 1, and the opening of the box 1 is in a state of being closed by the hatch 12. After the hatch 12 is opened, the driving member 21 drives the storage table 2 to move from the opening to the outside of the box 1, and then places the supporting frame 5 loaded with consumables 6 at the corresponding position on the storage table 2.

[0117] During the execution of the above steps, the storage table 2 is always located outside the box body 1, and the door 12 is in a closed state, so that the internal cavity of the box body 1 is isolated from the outside.

[0118] After completing the above steps, open the door 12, drive the storage table 2 to slide to the reaction position inside the box 1 through the driving member 21, and close the door 12 to isolate the inside of the box 1 from the outside, so as to avoid the aerosol generated during the extraction of nucleic acid from diffusing to the external area and causing contamination.

[0119] After the loading support bracket 5 of the storage table 2 moves to the reaction position, the shift drive 72 drives the shift plate 71 to slide along the second direction, so that the magnetic rod sleeve 32 moves to the position corresponding to the consumable hole 61 where the magnetic beads are placed; then the lifting drive 74 drives the magnetic rod sleeve 31 to slide along the third direction, driving the magnetic rod sleeve 32 and the magnetic rod 42 to move synchronously. During this process, the magnetic rod 42 remains stationary relative to the magnetic rod sleeve 32, and the two are in a state of separation from each other, driving the magnetic rod sleeve 32 to extend into the consumable hole 61 where the magnetic beads are stored, and driving the magnetic rod sleeve 32 to slide back and forth up and down to mix the magnetic beads; then the secondary drive 43 drives the magnetic rod 42 to slide relative to the magnetic rod sleeve 32, drives the magnetic rod 42 to be inserted into the corresponding magnetic rod sleeve 32, adsorbs the magnetic beads on the magnetic rod sleeve 32, and transfers the magnetic beads through the magnetic rod sleeve 32.

[0120] The lifting drive 74 drives the magnetic rod sleeve 32 and the magnetic rod 42 to move out of the consumable hole 61 for storing the magnetic beads. In the subsequent stage, the magnetic rod 42 and the magnetic rod sleeve 32 remain relatively still, and the magnetic beads are stably adsorbed on the surface of the magnetic rod sleeve 32. Driven by the lifting drive 74 and the shifting drive 72, the magnetic rod 42 and the magnetic rod sleeve 32 move synchronously in the third direction and the second direction.

[0121] After the magnetic beads are adsorbed on the surface of the magnetic rod sleeve 32, the magnetic beads are driven to move to the sample position, the magnetic rod sleeve 32 carries the magnetic beads and moves into the sample, the magnetic rod 42 is extracted from the magnetic rod sleeve 32 and remains separated, the magnetic rod sleeve 32 moves to oscillate and mix, and the sample is lysed; then the magnetic rod 42 moves, is inserted into the magnetic rod sleeve 32, and remains stationary with the magnetic rod sleeve 32, and the combination of magnetic beads and nucleic acids is kept adsorbed on the magnetic rod sleeve 32. In the process of shaking up and down and mixing, the temperature required for lysis is provided by the heating structure, and the temperature can be adaptively adjusted according to the different samples to be extracted in the actual operation; illustratively, the lysis temperature is adjusted to room temperature-120°C.

[0122] When actually performing oscillation mixing, the height of the magnetic rod sleeve 32 during mixing and different mixing amplitudes are set according to different sample volumes to achieve the best mixing effect. How to calculate the mixing height and the oscillation frequency during mixing according to the sample volume can be determined by those skilled in the art based on known techniques, and the present application embodiment will not specifically introduce the determination method.

[0123] Afterwards, the magnetic beads bound with nucleic acid are kept adsorbed on the magnetic rod sleeve 32 and transferred to the rinsing hole for up and down shaking and rinsing, and then the magnetic beads are driven to move in the air to dry; in this process, the magnetic beads can be rinsed multiple times according to actual needs to achieve a better rinsing effect.

[0124] Finally, the rinsed magnetic beads are carried to the elution wells, so that the nucleic acids on the magnetic beads are eluted and temporarily stored in the elution wells, waiting to be used in subsequent processes.

[0125] It should be explained that the above-mentioned lysis holes, rinsing holes and elution holes refer to the consumable holes 61 corresponding to lysis, rinsing and elution, and corresponding accommodation structures are provided at the corresponding hole positions. They are not simply open hole structures. For the sake of convenience of description, they are referred to as lysis holes, rinsing holes and elution holes for short.

[0126] In the above steps, the nucleic acid after elution is temporarily stored in the consumable hole 61 of the consumable 6, the hatch 12 is opened, and the driving member 21 drives the storage table 2 to slide to the access position outside the box 1, waiting for the subsequent other processes to use the extracted nucleic acid; and after the storage table 2 moves to the access position, the hatch 12 is closed, so that the internal cavity of the box 1 is sealed to reduce the contamination problem with the surrounding area.

[0127] 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.

[0128] 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 extraction instrument, characterized in that: It comprises a box body with a cavity formed inside, and the box body is composed of a bottom plate, side plates and a top plate; The nucleic acid extractor further comprises a storage table and a magnetic rod cover assembly and a magnetic rod assembly arranged in the cavity; wherein the storage table is used to carry the sample to be extracted and the reagents required for extraction, and the magnetic rod cover assembly and the magnetic rod assembly are used to carry the sample and transfer it between different extraction processes; The side panel is provided with an opening for the storage table to pass through; It also includes a driving member arranged at the lower side of the bottom plate, wherein a connecting hole is opened on the bottom plate along a first direction, and the driving member is connected to the storage platform through the connecting hole, and the storage platform is driven by the driving member to move between the pick-and-place position and the reaction position along the first direction; The side panel is provided with a door for opening and closing the opening, and the opening is closed when the storage table is located at the pick-and-place position or the reaction position; Wherein, the pick-and-place position is located outside the cavity, and the reaction position is located inside the cavity.

2. The nucleic acid extractor according to claim 1, characterized in that: The bottom plate is provided with a sealing belt for sealing the communicating hole.

3. The nucleic acid extractor according to claim 2, characterized in that: A rolling member is provided on one side of the storage platform facing the driving member, and the storage platform is connected to the driving member through the rolling member; The sealing belt cooperates with the rolling member to seal the communicating hole.

4. The nucleic acid extractor according to claim 3, characterized in that: The rolling member comprises a supporting block, a connecting block and a plurality of limiting rollers; The support blocks are provided with two, and are used to be connected with the driving member and the storage table; The connecting block and the limiting block are located between the two supporting blocks, and both ends of the connecting block and the limiting roller are connected to the supporting blocks; The sealing belt spans over the connecting block, and the limiting rollers are distributed on both sides of the connecting block to limit the sealing belt to remain in cooperation with the rolling member to seal the communicating hole.

5. The nucleic acid extractor according to any one of claims 1 to 4, characterized in that: The driving member includes a driving screw rotatably connected to the base plate, a sliding block sleeved on the driving screw, a driving motor connected to the driving screw at its output end, and a frame fixedly connected to the lower side of the base plate; the driving screw and the driving motor are connected to the frame; The sliding block is threadably matched with the driving lead screw and is fixedly connected to the storage table.

6. The nucleic acid extractor according to claim 1, characterized in that: Also included is a support frame and a number of consumables; Wherein, the support frame is carried on the storage table; A plurality of the consumables are arranged on the support frame along a first direction and are detachably connected to the support frame; Each of the consumables is provided with a plurality of consumable holes along the second direction, and the plurality of consumable holes are respectively used to store samples to be extracted and reagents required for extraction; The first direction is perpendicular to the second direction.

7. The nucleic acid extractor according to claim 1, characterized in that: The bottom plate is fixedly connected with a mounting frame, and the mounting frame is provided with a shifting component; The shift assembly comprises a shift plate slidably connected to the mounting frame along the second direction and a shift driving member arranged on the mounting frame, wherein the shift driving member is connected to the shift plate to drive the shift plate to slide; The magnetic rod sleeve assembly and the magnetic rod assembly are both arranged on the shift plate; The first direction is perpendicular to the second direction.

8. The nucleic acid extractor according to claim 7, characterized in that: The magnetic rod sleeve assembly comprises a magnetic rod sleeve frame and a plurality of magnetic rod sleeves arranged on the magnetic rod sleeve frame, and the magnetic rod sleeve frame is slidably connected with the shift plate along the third direction; The shift plate is also provided with a lifting drive member for driving the magnetic rod sleeve to slide relative to the shift plate; The magnetic rod assembly comprises a magnetic rod frame and a plurality of magnetic rods arranged on the magnetic rod frame, and the magnetic rod frame is slidably connected with the magnetic rod sleeve frame along a third direction; The magnetic rod frame is provided with a secondary driving member for driving the magnetic rod frame to slide relative to the magnetic rod sleeve frame; Wherein, the third direction is perpendicular to the bottom plate, and the plurality of magnetic rods correspond to the plurality of magnetic rod sleeves one by one.

9. The nucleic acid extractor according to claim 8, characterized in that: The secondary driving member includes a screw rod threadedly matched with the magnetic rod sleeve frame and a motor fixed relative to the magnetic rod frame, and the motor is used to drive the screw rod to rotate; The screw rod passes through the magnetic rod frame and is rotatably connected to the magnetic rod frame, and the magnetic rod frame and the screw rod are relatively fixed in the third direction.

10. A library preparation device, characterized in that: It comprises the nucleic acid extraction instrument as described in any one of claims 1 to 9.

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