Full-automatic all-in-one machine for NGS library establishment, hybridization sequencing and interpretation

Abstract

The invention relates to an NGS library building hybridization sequencing interpretation full-automatic all-in-one machine, which is used for sample adding and sequencing of a sequencing chip, and comprises a rack, and a manipulator, a library preparation instrument and a sequencing device which are arranged on the rack, the sequencing device comprises a gene sequencer, a sample adding clamping mechanism and a turnover mechanism, the library preparation instrument is used for sample adding of the sequencing chip, and the sample adding clamping mechanism is used for sample adding of the sequencing chip. The sample adding and clamping mechanism comprises a clamping tool and a clamping base, the clamping base is provided with a second positioning groove, the clamping tool is placed in the second positioning groove, the clamping tool clamps the sequencing chip, the overturning mechanism overturns the clamping tool to drive the sequencing chip for sample adding to overturn, the manipulator comprises an execution end and a clamping piece, the clamping piece is arranged at the execution end, and the clamping piece is arranged at the execution end. The clamping piece clamps the clamping tool, and the execution end moves among the library preparation instrument, the turnover mechanism and the gene sequencer, so that the sequencing chip is inserted into a preset position of the slot after being subjected to sample adding and turnover. The clamping tool clamps the sequencing chip, so that the sequencing chip is prevented from being overturned and falling off, automatic insertion of the sequencing chip is realized, and the sequencing efficiency is improved.

Description

Technical Field

[0001] The present invention relates to the technical field of microbiological instruments, and particularly to a fully automatic integrated machine for NGS library construction, hybridization sequencing and interpretation. Background Art

[0002] Next-generation sequencing technology (NGS), also known as high-throughput sequencing technology or second-generation sequencing technology, is characterized by the ability to simultaneously sequence hundreds of thousands to millions of DNA molecules at one time and generally having relatively short read lengths.

[0003] The detection process of high-throughput sequencing sequentially includes the following steps: sample preparation, library preparation, sequencing reaction, and data analysis. In the sequencing reaction step, it is necessary to manually load the sequencing chip with the sample, flip the sequencing chip, and then insert it into the slot of the gene sequencer for DNA molecule sequence determination. Especially on the production line, the library preparation is generally completed around 3 am, and it is necessary to specially arrange testers for sequencing on the machine, which poses a great challenge to the personnel scheduling and the human efficiency of the testing institution. The sequencing efficiency is low, and there are problems such as the sequencing chip falling off during flipping and the sequencing chip getting stuck. Therefore, there is an urgent need for a fully automatic integrated machine for NGS library construction, hybridization sequencing and interpretation to solve the above technical problems. Summary of the Invention

[0004] The purpose of the present invention is to provide a fully automatic integrated machine for NGS library construction, hybridization sequencing and interpretation to solve at least one of the above problems.

[0005] To achieve the above purpose, the present invention provides a fully automatic integrated machine for NGS library construction, hybridization sequencing and interpretation, which is used for adding samples to and sequencing a sequencing chip, and includes a frame, a manipulator, a library preparation instrument and a sequencing device arranged on the frame. The sequencing device includes a gene sequencer, a sample addition clamping mechanism and a flipping mechanism. The library preparation instrument can add samples to the sequencing chip; a slot for inserting the sequencing chip is provided on the gene sequencer;

[0006] The sample addition clamping mechanism includes a clamping tooling and a clamping base. A second positioning groove is provided on the clamping base, and the clamping tooling is placed in the second positioning groove. The clamping tooling is used to clamp the sequencing chip;

[0007] The flipping mechanism can flip the clamping tooling to drive the sequenced chip after sample addition to flip;

[0008] The manipulator includes an execution end and a clamping member. The clamping member can clamp the clamping tooling or the clamping base, and the execution end can move between the library preparation instrument, the flipping mechanism and the gene sequencer so that the sequencing chip is added with samples, flipped and then inserted into a preset position of the slot.

[0009] Further, the clamping tooling includes:

[0010] A fixing component, which includes a fixing piece and a locking and positioning piece. An installation groove is formed on the fixing piece, the locking and positioning piece is arranged in the installation groove, and a positioning part for positioning the sequencing chip is arranged on the locking and positioning piece;

[0011] An upper cover, one end of which is rotatably connected to the fixing piece and is used for switching between opening and closing the installation groove;

[0012] A reset component, which is arranged between the upper cover and the fixing component, and the reset component is used for automatically opening the unlocked upper cover;

[0013] A locking component, which is arranged between the upper cover and the fixing component, and the locking component is used for locking the closed upper cover;

[0014] When the upper cover is closed, the sequencing chip is clamped between the locking and positioning piece and the upper cover.

[0015] Further, the locking component includes:

[0016] A first locking connecting piece, which is arranged on the upper cover;

[0017] A second locking connecting piece, which is arranged on the fixing component. The first locking connecting piece and the second locking connecting piece can be buckled or opened. When the second locking connecting piece contacts the gene sequencer, the first locking connecting piece and the second locking connecting piece are opened.

[0018] Further, the first locking connecting piece includes a hook, and one end of the hook is connected to the upper cover;

[0019] The second locking connecting piece includes a hook connecting piece. A sliding groove is formed on the fixing piece below the locking and positioning piece, and one end of the hook connecting piece is slidably arranged in the sliding groove;

[0020] A card slot is formed on the hook connecting piece. When the second locking connecting piece contacts the gene sequencer, one end of the hook connecting piece slides in the sliding groove, so that the other end of the hook is separated from the card slot.

[0021] Further, the locking component further includes a locking spring, which is used for keeping the hook and the card slot in a clamped state. One end of the hook connecting piece is connected to one end of the locking spring, and the other end of the locking spring is connected to the groove wall of the sliding groove.

[0022] Furthermore, the upper cover and the fixing member are rotatably connected via a rotating shaft, and the reset assembly comprises:

[0023] A torsion spring mounting member, which is rotatably mounted on the rotating shaft, and the torsion spring mounting member is connected to the upper cover;

[0024] The torsion spring is sleeved on the rotating shaft and installed on the torsion spring mounting piece.

[0025] Furthermore, the sample adding and clamping mechanism further comprises a clamping base and a sample adding seat, the clamping base is provided with a second positioning groove, and the clamping tool is placed in the second positioning groove;

[0026] The sequencing chip is provided with a sample loading port, the sample loading seat is located on one side of the sample loading port, and the clamping tool is located on the opposite side of the sequencing chip;

[0027] A side positioning protrusion is provided on the side wall of one end of the sequencing chip extending out of the clamping tool;

[0028] The sample adding seat is placed on the clamping base, an open slot is arranged on the sample adding seat, and the side positioning protrusion is clamped in the open slot.

[0029] Furthermore, the manipulator further comprises a chip pushing mechanism, which is connected to the execution end and is used to push the stuck sequencing chip to a preset position of the slot, and the chip pushing mechanism comprises:

[0030] Push the base;

[0031] A Z-direction adjustment component, the Z-direction adjustment component is disposed on one side of the pushing base, and the Z-direction adjustment component includes a Z-direction moving component movable along the Z direction; and

[0032] A pushing component, the pushing component is fixedly arranged on a side of the Z-direction moving component away from the pushing base, and the pushing component includes:

[0033] A pushing surface, the pushing surface is located at a side of the pushing component away from the Z-moving component, and the pushing surface is perpendicular to the X direction;

[0034] A first toggle block, the first toggle block extending from one end of the pushing surface in the Z direction along the X direction and away from the Z-direction moving component; and

[0035] A second toggle block extends from the other end of the pushing surface in the Z direction along the X direction and away from the Z-direction moving component.

[0036] Furthermore, the flipping mechanism comprises:

[0037] A flipping drive assembly, the flipping drive assembly includes a rotary drive member and a clamping drive member connected to each other, the rotary drive member is configured to drive the clamping drive member to rotate around a rotation axis, the clamping drive member has a first execution end and a second execution end, and at least one of the first execution end and the second execution end is configured to be movable between a clamping position and a relaxation position;

[0038] A first jaw, the first jaw is arranged at the first execution end; and

[0039] A second jaw, the second jaw is arranged at the second execution end,

[0040] wherein, a clamping area is formed between the first jaw and the second jaw, a first clamping positioning member is arranged on a side of the first jaw facing the clamping area, and a second clamping positioning member is arranged on a side of the second jaw facing the clamping area.

[0041] Furthermore, the fully automatic integrated machine for NGS library construction hybridization sequencing interpretation further includes a low-temperature storage mechanism, and the low-temperature storage mechanism includes:

[0042] An anti-condensation water component, which includes a storage mounting seat, a pressing cover member and a slow-elastic member, the storage mounting seat is provided with a mounting surface, the pressing cover member is mounted on the mounting surface, a first end of the slow-elastic member is mounted on the mounting surface, the pressing cover member has a first state and a second state, when the pressing cover member is in the first state, both the pressing cover member and a second end of the slow-elastic member abut against a sealing surface of a consumable cartridge; when the pressing cover member is in the second state, the pressing cover member is away from the sealing surface of the consumable cartridge, and the second end of the slow-elastic member extends beyond the pressing cover member and abuts against the sealing surface of the consumable cartridge;

[0043] A refrigeration component, which includes a support frame and a refrigeration member, the support frame places the consumable cartridge, and the refrigeration member refrigerates the consumable cartridge;

[0044] A storage drive component, which drives the storage mounting seat to move up and down relative to the support frame.

[0045] The beneficial effects of the present invention are:

[0046] The fully automatic integrated machine for NGS library construction, hybridization sequencing and interpretation provided by the present invention is used for loading samples and sequencing a sequencing chip, and includes a frame, a manipulator, a sequencing device and a library preparation instrument arranged on the frame. The sequencing device includes a gene sequencer, a sample loading clamping mechanism and a flipping mechanism. The library preparation instrument can load samples for the sequencing chip. A slot for inserting the sequencing chip is provided on the gene sequencer. The sample loading clamping mechanism includes a clamping tooling and a clamping base. A second positioning groove is provided on the clamping base, and the clamping tooling is placed in the second positioning groove. The clamping tooling is used to clamp the sequencing chip. The flipping mechanism can flip the clamping tooling to drive the loaded sequencing chip to flip. The manipulator includes an execution end and a clamping member. The clamping member is arranged at the execution end. The clamping member can clamp the clamping tooling or the clamping base. The execution end can move among the library preparation instrument, the flipping mechanism and the gene sequencer so that the sequencing chip is loaded, flipped and then inserted into a preset position of the slot. First, the manipulator clamps the sample loading clamping mechanism and moves it into the library preparation instrument for sample loading. Then, the manipulator clamps the clamping base and moves it to the flipping mechanism. The clamping base drives the loaded sequencing chip together with the clamping tooling to also move to the flipping mechanism. The flipping mechanism clamps the clamping tooling so that the clamping tooling is separated from the clamping base. The flipping mechanism flips the clamping tooling so that the loaded sequencing chip follows the clamping tooling to flip. Then, the manipulator moves the flipped clamping tooling and the sequencing chip to the gene sequencer, and drives the sequencing chip to be inserted into the slot through the movement of the execution end of the manipulator. The clamping tooling clamps the sequencing chip, and the flipping mechanism flips the clamping tooling together with the sequencing chip, which can prevent the sequencing chip from falling during flipping. The cooperation of the sequencing device, the manipulator and the library preparation instrument realizes the automatic insertion of the sequencing chip, eliminates the need for specially arranging testers for manual sequencing on the machine, eliminates the need for arranging personnel shifts, and improves the sequencing efficiency. BRIEF DESCRIPTION OF THE DRAWINGS

[0047] Figure 1 is the top view of the fully automatic integrated machine for NGS library construction, hybridization sequencing and interpretation provided by an embodiment of the present invention;

[0048] Figure 2 is the structural schematic diagram of the fully automatic integrated machine for NGS library construction, hybridization sequencing and interpretation provided by an embodiment of the present invention;

[0049] Figure 3 is the schematic diagram of a partial structure of the manipulator and the sequencing device provided by an embodiment of the present invention;

[0050] Figure 4 is the structural schematic diagram of the clamping tooling in the closed state provided by an embodiment of the present invention;

[0051] Figure 5 is the structural schematic diagram of the clamping tooling in the open state at a first angle provided by an embodiment of the present invention;

[0052] Figure 6It is a schematic structural diagram of the second angle of the clamping tooling provided by the embodiment of the present invention in the open state;

[0053] Figure 7 It is a cross-sectional view of the clamping tooling provided by the embodiment of the present invention;

[0054] Figure 8 It is a schematic structural diagram of the positioning member provided by the embodiment of the present invention;

[0055] Figure 9 It is a schematic structural diagram of the first angle of the sequencing chip provided by the embodiment of the present invention;

[0056] Figure 10 It is a schematic structural diagram of the second angle of the sequencing chip provided by the embodiment of the present invention;

[0057] Figure 11 It is a schematic structural diagram of the sample loading clamping mechanism provided by the embodiment of the present invention;

[0058] Figure 12 It is a schematic structural diagram of the clamping base provided by the embodiment of the present invention;

[0059] Figure 13 It is a schematic structural diagram of the sample loading clamping mechanism with the sample loading seat removed provided by the embodiment of the present invention;

[0060] Figure 14 It is a schematic structural diagram of the first angle of the sample loading seat provided by the embodiment of the present invention;

[0061] Figure 15 It is a schematic structural diagram of the second angle of the sample loading seat provided by the embodiment of the present invention;

[0062] Figure 16 It is a cross-sectional view of the sample loading seat provided by the embodiment of the present invention;

[0063] Figure 17 It is a schematic diagram of the gene sequencer, sequencing chip and chip pushing mechanism provided by the embodiment of the present invention;

[0064] Figure 18 It is a schematic diagram of the chip pushing mechanism provided by the embodiment of the present invention;

[0065] Figure 19 It is an exploded view of the chip pushing mechanism provided by the embodiment of the present invention;

[0066] Figure 20 It is a cross-sectional view of the pushing base and the X-direction buffer assembly provided by the embodiment of the present invention;

[0067] Figure 21 It is a perspective view of the flipping mechanism provided by the embodiment of the present invention, wherein the clamping tooling is located between the first jaw and the second jaw;

[0068] Figure 22 is a right side view of the flipping mechanism provided by an embodiment of the present invention;

[0069] Figure 23 is a perspective view of a flip mechanism provided by another embodiment of the present invention;

[0070] Figure 24 is a schematic structural diagram of an anti-condensation water assembly provided in an embodiment of the present invention;

[0071] Figure 25 is an exploded view of an anti-condensation water assembly provided by an embodiment of the present invention;

[0072] Figure 26 is a cross-sectional view of a partial structure of an anti-condensation water assembly provided by an embodiment of the present invention;

[0073] Figure 27 Yes Yes Figure 26 A partial enlarged view of the middle A;

[0074] Figure 28 is a schematic structural diagram of a spring-absorbing member provided in an embodiment of the present invention;

[0075] Figure 29 is a schematic structural diagram of a fixing base provided by an embodiment of the present invention;

[0076] Figure 30 is a schematic structural diagram of a low-temperature storage mechanism provided by an embodiment of the present invention;

[0077] Figure 31 is a structural schematic diagram of a part of the structure of a low-temperature storage mechanism provided by an embodiment of the present invention;

[0078] Figure 32 It is a schematic structural diagram of a part of the low-temperature storage mechanism provided by an embodiment of the present invention from another angle.

[0079] In the figure:

[0080] 1. Frame;

[0081] 2. Manipulator; 21. Executing end; 22. Clamping member; 23. Chip pushing mechanism; 231. Pushing base; 2311. X-direction channel; 232. Z-direction adjustment assembly; 2321. Z-direction moving component; 2322. Z-direction mounting seat; 23221. First mounting block; 23222. Second mounting block; 2323. Z-direction guiding component; 2324. Z-direction elastic component; 233. Pushing component; 2331. Pushing surface; 2332. First toggle block; 23321. First toggle surface; 2333. Second toggle block; 23331. Second toggle surface; 234. X-direction buffer assembly; 2341. X-direction moving component; 2342. X-direction guiding component; 2343. X-direction elastic component;

[0082] 3. Sequencing device;

[0083] 31. Gene sequencer; 311. Slot;

[0084] 32. Sequencing chip; 321. End positioning protrusion; 322. Sampling port; 323. Side positioning protrusion;

[0085] 33. Sampling clamping mechanism; 330. Clamping tooling; 331. Fixing component; 3310. Installation groove; 3311. Fixing piece; 33111. Clamping hole; 33112. Sliding groove; 33113. Locking insertion cavity; 3312. Locking positioning piece; 33121. Positioning part; 33122. First arc surface; 33123. First positioning groove; 33124. Locking avoidance groove; 332. Upper cover; 333. Reset component; 3331. Torsion spring mounting piece; 3332. Torsion spring; 334. Locking component; 3341. First locking connecting piece; 33411. Hook; 3342. Second locking connecting piece; 33421. Hook connecting piece; 334211. Card slot; 334212. Second arc surface; 334213. Limit hole; 3343. Locking spring; 3345. Limiting piece; 336. Clamping base; 3361. Second positioning groove; 3362. First observation window; 3363. Second observation window; 3364. Positioning wall; 3365. Weight reduction hole; 337. Sampling seat; 3371. Open card slot; 3372. Sampling channel; 3373. Open positioning card slot; 338. Rotating shaft;

[0086] 34. Flipping mechanism; 341. Flipping fixed seat; 3411. Installation hole; 342. Flipping driving component; 3421. Rotation driving part; 3422. Clamping driving part; 34221. First execution end; 34222. Second execution end; 3423. Rotation axis; 343. First clamping jaw; 344. Second clamping jaw; 3441. Second clamping positioning piece; 345. Connection component; 3451. First flipping connecting piece; 3452. Second flipping connecting piece; 346. Sensor component; 3461. Groove type optoelectronic switch; 3462. Switch baffle; 3463. Switch mounting seat;

[0087] 4. Library preparation instrument; 41. Conveyor module; 42. Inlet and outlet;

[0088] 5. Storage device; 51. Room temperature storage mechanism;

[0089] 52. Low temperature storage mechanism;

[0090] 521. Anti-condensation component; 5211. Storage and installation base; 52111. Installation part; 521111. Fixed groove; 521112. First guiding groove; 521113. Installation surface; 52112. Connection part; 5212. Pressing cover component; 52121. Pressing plate; 521211. First avoidance groove; 52122. Elastic pad; 521221. Second avoidance groove; 5213. Elastic buffer component; 52131. Elastic buffer element; 521311. Guiding part; 521312. Pressing part; 52132. Elastic buffer fixing seat; 521321. Movable groove; 521322. Second guiding groove; 521323. Fastening groove; 521324. Fixing part; 521325. Protruding part; 52133. Elastic element; 5214. Buffer part; 5215. Fastening piece; 522. Storage driving component; 5221. Storage driving board; 5222. Storage driving piece; 5223. Installation board; 5224. Connection block; 523. Refrigeration component; 5231. Support frame; 5232. Refrigeration piece; 524. Machine shell;

[0091] 6. Consumable cartridge;

[0092] 7. Fluorescence quantitative detection device;

[0093] 8. Calibration device;

[0094] 9. Film sealing device. Detailed implementation manners

[0095] The technical solutions of the present invention will be further described below in conjunction with the accompanying drawings and through specific implementation manners. It can be understood that the specific embodiments described herein are only used to explain the present invention, rather than limiting the present invention. Additionally, it should be noted that for the convenience of description, only parts related to the present invention are shown in the drawings, rather than all of them.

[0096] Some orientation words are defined in the present invention. Without contrary explanations, the orientation words such as "upper", "lower", "left", "right", "inner", and "outer" are used for convenience of understanding, and thus do not constitute a limitation to the protection scope of the present invention.

[0097] In the present invention, unless otherwise clearly defined and limited, the first feature being "above" or "below" the second feature may include direct contact between the first and second features, or may include the situation where the first and second features are not in direct contact but in contact through other features between them. Moreover, the first feature being "above", "over", and "on" the second feature includes the first feature being directly above and obliquely above the second feature, or simply indicating that the first feature is at a higher horizontal height than the second feature. The first feature being "below", "under", and "beneath" the second feature includes the first feature being directly below and obliquely below the second feature, or simply indicating that the first feature is at a lower horizontal height than the second feature.

[0098] In the description of the present invention, unless otherwise clearly defined and limited, the terms "connected", "connected to", and "fixed" shall be understood in a broad sense. For example, it may be a fixed connection, a detachable connection, or integrated; it may be a mechanical connection or an electrical connection; it may be directly connected or indirectly connected through an intermediate medium, and it may be the internal communication of two components or the interaction relationship between two components. For those of ordinary skill in the art, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0099] As Figures 1 - 32 shown, this embodiment provides a fully automatic integrated machine for NGS (Next-Generation Sequencing) library construction, hybridization sequencing, and interpretation, which is used for library preparation of samples, loading sequencing chips 32, automatic sequencing, and data analysis, so as to detect genetic diseases, tumor mutations, and pathogenic microorganism infections. The whole process of the fully automatic integrated machine for NGS library construction, hybridization sequencing, and interpretation provided in this embodiment is from the sample in the nucleic acid state to the automatic output of the detection report, and the whole process is unattended.

[0100] As Figures 1 - 2 shown, the fully automatic integrated machine for library construction, hybridization sequencing, and interpretation includes a frame 1, a manipulator 2, a sequencing device 3, a library preparation instrument 4, a storage device 5, a fluorescence quantitative detection device 7, a calibration device 8, and a film sealing device 9. The manipulator 2, the sequencing device 3, the library preparation instrument 4, the storage device 5, the fluorescence quantitative detection device 7, the calibration device 8, and the film sealing device 9 are all arranged on the frame 1. Materials are stored in the storage device 5. The manipulator 2 is used to transport materials between the sequencing device 3, the library preparation instrument 4, the storage device 5, the fluorescence quantitative detection device 7, the calibration device 8, and the film sealing device 9. The fluorescence quantitative detection device 7 is used for concentration measurement. The calibration device 8 is used for position calibration. The film sealing device 9 is used for sealing the consumable cartridge 6. The preparation of the sample library is mainly realized through the manipulator 2, the library preparation instrument 4, the storage device 5, the fluorescence quantitative detection device 7, the calibration device 8, and the film sealing device 9. The sequencing device 3 cooperates with the manipulator 2 and the library preparation instrument 4 to sequence the gene fragments of the prepared library sample. Specifically, the sequencing device 3 includes a gene sequencer 31. After the sequencing chip 32 is loaded and flipped, it is inserted into the gene sequencer 31 for gene fragment sequencing. The library preparation instrument 4 is used for library preparation of samples and loading the sequencing chip 32.

[0101] In this embodiment, the consumable cartridge 6, the reagent kit, the sequencing chip 32, and the used instruments can all be called materials. The used instruments may include the sample loading clamping mechanism 33 described below. The consumable cartridge 6 can store the collected initial samples, intermediate products, and final products of the reaction, etc.

[0102] Further, the storage device 5 includes a normal-temperature storage mechanism 51 and a low-temperature storage mechanism 52. The normal-temperature storage mechanism 51 is used to store materials that do not require refrigeration, and the low-temperature storage mechanism 52 is used to store materials that require refrigeration.

[0103] Further, as Figure 3 shown, the manipulator 2 can be a multi-axis manipulator. The manipulator 2 includes a clamping member 22. The clamping member 22 is used to clamp materials. The clamping member 22 can move to any position within a three-dimensional space so that the manipulator 2 can transport materials between various devices for the purpose of detection.

[0104] Further, the library preparation instrument 4 includes a transfer module 41 and an inlet / outlet 42. The transfer module 41 extends out of the library preparation instrument 4 from the inlet / outlet 42. The transfer module 41 is used to input or output materials to / from the library preparation instrument 4, and the inlet / outlet 42 is for materials to enter and exit the library preparation instrument 4.

[0105] It should be noted that the structures and working principles of the manipulator 2, the library preparation instrument 4, the fluorescence quantitative detection device 7, the calibration device 8, and the film sealing device 9 are prior arts and can be directly purchased and used, and will not be elaborated in the present invention.

[0106] The preparation process of the sample library is specifically as follows:

[0107] Step 1 (library preparation): Manually place the consumable box 6 containing the initial sample, the reagent kit required for library preparation, and an empty consumable box 6 into the library preparation instrument 4, and place the reagent kit, the consumable box 6, and the sample loading clamping mechanism 33 equipped with the sequencing chip 32 required in the subsequent steps (such as the sequencing step) of library preparation into the storage device 5. The library preparation instrument 4 performs experiments such as pipetting, amplification, purification, hybridization, and washing on the required reagents and the initial sample, and finally injects the prepared sample library into the empty consumable box 6;

[0108] Step 2 (consumable loading and unloading): For the consumable box 6 that is no longer used in the subsequent steps of library preparation, output it from the library preparation instrument 4 through the transfer module 41. The manipulator 2 clamps the above-mentioned consumable box 6 and places it on the calibration device 8 for position calibration, and then the manipulator 2 places the calibrated consumable box 6 into the storage device 5; for the reagent kit 6, the consumable box 6, and the sample loading clamping mechanism 33 required in the subsequent steps of library preparation, the manipulator 2 clamps the above-mentioned materials from the storage device 5 and places them on the calibration device 8 for position calibration, and then the manipulator 2 places the calibrated materials into the transfer module 41 and inputs them into the library preparation instrument 4 through the transfer module 41;

[0109] Step 3 (Library Quality Control): The library preparation instrument 4 prepares a concentration detection system for the prepared library in the empty consumable cartridge 6, adds a part of the prepared library into the concentration detection system, the oscillation module mixes the concentration detection system, and then outputs the consumable cartridge 6 filled with the concentration detection system from the library preparation instrument 4 through the transfer module 41. The manipulator 2 grips the consumable cartridge 6 filled with the concentration detection system and places it on the calibration device 8 for position calibration. Then, the manipulator 2 places the calibrated consumable cartridge 6 on the fluorescence quantitative detection device 7, and the fluorescence quantitative detection device 7 detects the concentration of specific target molecules in the concentration detection system in the consumable cartridge 6;

[0110] Step 4 (Library Mixing and Preparation of DNB (DNA NanoBalls, i.e., the product to be sequenced)): The library with a known concentration after detection is pipetted in the library preparation instrument 4 for library pooling, thereby preparing a mixed product. The library preparation instrument 4 performs experiments such as pipetting and amplification on the mixed product, and finally outputs the product to be sequenced.

[0111] The consumable cartridges 6 containing the library and the product to be sequenced can be gripped by the gripper 22 of the manipulator 2 on the transfer module 41 and placed in the calibration device 8. After position calibration, the consumable cartridge 6 is gripped by the manipulator 2 and placed in the film sealing device 9 for film sealing. The manipulator 2 places the film-sealed consumable cartridge 6 back into the storage device 5.

[0112] Inject the product to be sequenced produced by the library preparation instrument 4 into the sequencing chip 32, and insert the loaded sequencing chip 32 into the gene sequencer 31 for gene fragment sequencing.

[0113] Such as Figure 3As shown, the fully automatic integrated machine for NGS library construction hybridization sequencing interpretation can be used for loading and sequencing the sequencing chip 32. The sequencing device 3 includes a gene sequencer 31, a sample loading clamping mechanism 33 and a flipping mechanism 34. A slot 311 for inserting the sequencing chip 32 is provided on the gene sequencer 31. The library preparation instrument 4 adds the library sample into the sequencing chip 32. The sample loading clamping mechanism 33 includes a clamping tooling 330 and a clamping base 336. A second positioning groove 3361 is provided on the clamping base 336. The clamping tooling 330 is placed in the second positioning groove 3361. The clamping tooling 330 is used to clamp the sequencing chip 32. The flipping mechanism 34 can flip the clamping tooling 330 to drive the loaded sequencing chip 32 to flip. The manipulator 2 further includes an execution end 21. A clamping member 22 is provided on the execution end 21. The clamping member 22 can clamp the clamping tooling 330 or the clamping base 336. The execution end 21 can move between the library preparation instrument 4, the flipping mechanism 34 and the gene sequencer 31, so that after the sequencing chip 32 is loaded and flipped, it is inserted into the preset position of the slot 311. First, the manipulator 2 clamps the sample loading clamping mechanism 33 and moves it into the library preparation instrument 4 for loading. Then, the manipulator 2 clamps the clamping base 336 and moves it to the flipping mechanism 34. The clamping base 336 drives the loaded sequencing chip 32 together with the clamping tooling 330 to also move to the flipping mechanism 34. The flipping mechanism 34 clamps the clamping tooling 330, so that the clamping tooling 330 is separated from the clamping base 336. The flipping mechanism 34 flips the clamping tooling 330, so that the loaded sequencing chip 32 follows the clamping tooling 330 to flip. Then, the manipulator 2 moves the flipped clamping tooling 330 and the sequencing chip 32 to the gene sequencer 31, and drives the sequencing chip 32 to be inserted into the slot 331 through the movement of the execution end 21 of the manipulator 2. The clamping tooling 330 clamps the sequencing chip 32, and the flipping mechanism 34 flips the clamping tooling 330 together with the sequencing chip 32, which can prevent the sequencing chip 32 from falling during flipping. The cooperation of the sequencing device 3, the manipulator 2 and the library preparation instrument 4 realizes the automatic insertion of the sequencing chip 32, eliminates the need for special arrangement of testers for manual sequencing on the machine, and eliminates the need for personnel scheduling, improving the sequencing efficiency.

[0114] The sequencing chip 32 is generally rectangular parallelepiped. In this embodiment, the length direction of the sequencing chip 32 is defined as the X direction, the width direction of the sequencing chip 32 is defined as the Y direction, and the thickness direction of the sequencing chip 32 is defined as the Z direction. Any two of the X direction, the Y direction and the Z direction are perpendicular to each other.

[0115] After the sequencing chip 32 is pre-inserted into the slot 311, the manipulator 2 drives the clamping tooling 330 to separate from the sequencing chip 32. Subsequently, the manipulator 2 drives the clamping tooling 330 separated from the sequencing chip 32 to move along the X direction, that is, the execution end 21 has at least the freedom to move along the X direction. The clamping tooling 330 will push one end of the sequencing chip 32 outside the slot 311 along the X direction, so that the sequencing chip 32 is inserted into the preset position of the slot 311. However, during the process of inserting the sequencing chip 32 into the slot 311, the gene sequencer 31 will apply a pressure along the Z direction to the surface of the sequencing chip 32, so that the sequencing chip 32 can reach the preset position after moving along the Z direction. Sometimes, only using the clamping tooling 330 to push the sequencing chip 32 along the X direction will cause the sequencing chip 32 to be stuck at a certain position in the slot 311 and cannot move along the Z direction.

[0116] To solve the problem of jamming during the insertion of the sequencing chip 32, the manipulator 2 further includes a chip pushing mechanism 23. The chip pushing mechanism 23 is arranged at the execution end 21, and the chip pushing mechanism 23 can push the jammed sequencing chip 32 to the preset position of the slot 311. When the sequencing chip 32 gets jammed, the execution end 21 drives the chip pushing mechanism 23 to move, so that the chip pushing mechanism 23 pushes the sequencing chip 32 to the preset position of the slot 311.

[0117] Specifically, as Figure 3 shown, both the clamping member 22 and the chip pushing mechanism 23 are connected to the execution end 21. When the sequencing chip 32 gets jammed, the execution end 21 rotates to make the chip pushing mechanism 23 face the slot 311, and the manipulator 2 drives the chip pushing mechanism 23 to insert the jammed sequencing chip 32 into the preset position of the slot 311.

[0118] The execution end 21 has at least the freedom to rotate around the axis extending along the Z direction, so that the clamping member 22 and the chip pushing mechanism 23 can face the slot 311 through rotation, in order to pre-insert the sequencing chip 32 clamped on the clamping tooling 330 into the slot 311, or use the chip pushing mechanism 23 to insert the jammed sequencing chip 32 into the preset position of the slot 311.

[0119] As Figures 4 - 16 shown, the sample loading clamping mechanism 33 is used for guiding the sample loading of the sequencing chip 32 and clamping the sequencing chip 32, and the sample loading clamping mechanism 33 is stored in the normal temperature storage mechanism 51. Among them, the sample loading clamping mechanism 33 further includes a sample loading seat 337, and the clamping tooling 330 is used for clamping the sequencing chip 32. Both the sample loading seat 337 and the clamping tooling 330 are arranged on the clamping base 336. When the library preparation instrument 4 loads the sample for the sequencing chip 32 clamped on the clamping tooling 330, the sample loading seat 337 plays a role in guiding the sample loading.

[0120] The clamping base 336 is provided with a second positioning groove 3361, and the clamping tooling 330 is placed in the second positioning groove 3361. The clamping tooling 330 is used to clamp the sequencing chip 32. The clamping tooling 330 is placed in the second positioning groove 3361 of the clamping base 336, and the clamping base 336 positions the clamping tooling 330, thereby ensuring the position accuracy of the sequencing chip 32. The clamping base 336 can be used as a positioning reference during sample addition of the library preparation instrument 4 to ensure the accuracy of sample addition.

[0121] The sample addition seat 337 is also placed on the clamping base 336. A side positioning protrusion 323 is provided on the side wall of one end of the sequencing chip 32 that extends out of the clamping tooling 330, and an open slot 3371 that engages with the side positioning protrusion 323 is provided on the sample addition seat 337. Through the mutual cooperation of the open slot 3371 and the side positioning protrusion 323, the position accuracy between the sample addition seat 337 and the sequencing chip 32 is ensured.

[0122] A sample addition port 322 is provided on the sequencing chip 32. The sample addition seat 337 is located on one side of the sample addition port 322, and the clamping tooling 330 is located on the opposite side of the sample addition seat 337.

[0123] After the position of the sample addition seat 337 is determined, the library preparation instrument 4 adds samples into the sequencing chip 32 through the sample addition seat 337. After sample addition is completed, the sample addition seat 337 is removed within the library preparation instrument 4, and the clamping tooling 330 clamps the sequencing chip 32 to prepare for detecting the sequencing chip 32.

[0124] Preferably, the side positioning protrusion 323 is a cylinder provided on the side surface of the sequencing chip 32.

[0125] The above-mentioned open slot 3371 is a square slot opening downward provided on the lower surface of the sample addition seat 337.

[0126] Preferably, a sample addition channel 3372 communicating with the sample addition port 322 is provided on the sample addition seat 337, and the diameter of the sample addition channel 3372 gradually decreases from the upper end opening downward. When the library preparation instrument 4 adds samples to the sequencing chip 32 clamped by the clamping tooling 330, the sample first enters the sample addition channel 3372 and then enters the sample addition port 322. The diameter of the sample addition channel 3372 gradually decreases from the upper end opening downward. Adding samples to the sample addition port 322 of the sequencing chip 32 through the sample addition channel 3372 on the sample addition seat 337 is more convenient for sample addition.

[0127] Preferably, a weight reduction hole 3365 is provided on the clamping base 336 to reduce the weight of the clamping base 336.

[0128] Preferably, a first observation window 3362 is formed on the clamping base 336. The position of the first observation window 3362 is opposite to the side positioning protrusion 323. The first observation window 3362 is used to observe whether the cooperation between the opening clamping groove 3371 of the sample adding seat 337 and the side positioning protrusion 323 is in place.

[0129] In this embodiment, two sample adding ports 322 are provided on the sequencing chip 32, and both of the two sample adding ports 322 can be used for sample addition.

[0130] Preferably, a second observation window 3363 is formed on the clamping base 336. The position of the second observation window 3363 is opposite to the sample adding detection area of the sequencing chip 32. The second observation window 3363 is used to observe whether the sample in the sample adding detection area of the sequencing chip 32 flows from one sample adding port 322 to the other sample adding port 322.

[0131] Preferably, positioning walls 3364 are symmetrically arranged on both sides of the clamping base 336. The positioning walls 3364 are located on the front side of the second positioning groove 3361. An opening positioning clamping groove 3373 is formed on the sample adding seat 337, and the opening positioning clamping groove 3373 is clamped on the positioning walls 3364.

[0132] Preferably, the clamping tooling 330 has an open state and a closed state. When the clamping tooling 330 contacts the gene sequencer 31, it will trigger the clamping tooling 330 to switch from the closed state to the open state. When the clamping tooling 330 is in the closed state, the clamping tooling 330 clamps the sequencing chip 32. The clamping tooling 330 includes a fixing component 331, an upper cover 332, a reset component 333 and a locking component 334. The fixing component 331 includes a fixing part 3311 and a locking positioning part 3312. An installation groove 3310 is formed on the fixing part 3311, the locking positioning part 3312 is arranged in the installation groove 3310, and a positioning part 33121 for positioning the sequencing chip 32 is arranged on the locking positioning part 3312.

[0133] One end of the upper cover 332 is rotatably connected to the fixing part 3311 and is used to switch between opening or closing the installation groove 3310.

[0134] The reset component 333 is arranged between the upper cover 332 and the fixing component 331, and the reset component 333 is used to drive the upper cover 332 to automatically open after the locking component 334 unlocks the upper cover 332.

[0135] The locking component 334 is arranged between the upper cover 332 and the fixing component 331, and the locking component 334 is used to lock the closed upper cover 332.

[0136] When the upper cover 332 is closed, the sequencing chip 32 is clamped between the fixing component 331 and the upper cover 332.

[0137] In this embodiment, the upper cover 332 can rotate relative to the fixed component 331 and can be opened or closed. The reset component 333 is used to automatically open the unlocked upper cover 332. When the upper cover 332 is closed, the locking component 334 locks the upper cover 332. When the upper cover 332 is locked, the sequencing chip 32 is clamped between the locking and positioning member 3312 and the upper cover 332. When the clamping tooling 330 and the sequencing chip 32 are transferred or flipped, it is ensured that the sequencing chip 32 will not fall off.

[0138] During the process of inserting the sequencing chip 32 into the slot 311 of the gene sequencer 31, the locking component 334 is triggered to unlock due to the abutment of the locking component 334 against the outer shell near the slot 311 of the gene sequencer 31. Subsequently, the upper cover 332 automatically opens under the action of the reset component 333.

[0139] In this embodiment, only after the clamping tooling 330 and the sequencing chip 32 are synchronously flipped 180° by the flipping mechanism 34 can the sequencing chip 32 be inserted into the slot 311 of the gene sequencer 31 for detection, ensuring that the position of the sequencing chip 32 will not change during the flipping process.

[0140] Preferably, the upper cover 332 and the fixing member 3311 are rotationally connected through a rotating shaft 338. Connecting the upper cover 332 and the fixing member 3311 through the rotating shaft 338 has a simple structure and is convenient for processing.

[0141] Preferably, the reset component 333 includes a torsion spring mounting member 3331 and a torsion spring 3332. Among them, the torsion spring mounting member 3331 is rotatably mounted on the rotating shaft 338, and the torsion spring mounting member 3331 is connected to the upper cover 332. The torsion spring 3332 is sleeved on the rotating shaft 338 and is mounted on the torsion spring mounting member 3331.

[0142] The torsion spring 3332 is used to push the torsion spring mounting member 3331 and the upper cover 332 to rotate synchronously along the rotating shaft 338, so that the upper cover 332 automatically opens. This structure is simple, convenient for installation, and has a low cost.

[0143] Preferably, the locking component 334 includes a first locking connecting member 3341 and a second locking connecting member 3342. Among them, the first locking connecting member 3341 is disposed on the upper cover 332, the second locking connecting member 3342 is disposed on the fixed component 331, and the first locking connecting member 3341 and the second locking connecting member 3342 can be buckled or opened. When the second locking connecting member 3342 contacts the gene detector 31, the first locking connecting member 3341 and the second locking connecting member 3342 are opened, thereby triggering the unlocking of the locking component 334. The first locking connecting member 3341 and the second locking connecting member 3342 are buckled to lock the upper cover 332. Specifically, the second locking connecting member 3342 is disposed on the fixing member 3311.

[0144] Preferably, the first locking connection member 3341 includes a hook 33411, one end of the hook 33411 is connected to the upper cover 332, the second locking connection member 3342 includes a hook connection member 33421, a sliding groove 33112 is formed in the fixing member 3311 below the locking positioning member 3312, a card slot 334211 is formed in the hook connection member 33421, the first end of the hook connection member 33421 is located outside the sliding groove 33112, the second end of the hook connection member 33421 extends into the sliding groove 33112 and can be clamped in the card slot 334211. When the second locking connection member 3342 contacts the gene detector 31, the second end of the hook connection member 33421 slides in the sliding groove 33112, so that the other end of the hook 33411 is separated from the card slot 334211, thereby triggering the unlocking of the locking assembly 334.

[0145] The locking assembly 334 further includes a locking spring 3343, the locking spring 3343 is used to keep the hook 33411 and the card slot 334211 in a clamped state, one end of the locking spring 3343 is connected to the locking spring 3343, and the other end of the locking spring 3343 is connected to the groove wall of the sliding groove 33112.

[0146] Specifically, the number of the hooks 33411 is two, the two hooks 33411 are located on both sides of the sequencing chip 32 along the Y direction, and the hooks 33411 are arranged in one-to-one correspondence with the hook connection members 33421.

[0147] Specifically, a hook groove is formed in the hook 33411, and the hook groove can be clamped on the groove side wall of the card slot 334211 (such as Figure 7 the left groove side wall). When the locking assembly 334 locks the closed upper cover 332, the locking spring 3343 is in a compressed state, and the locking spring 3343 makes the groove side wall of the card slot 334211 tightly clamped in the hook groove, so that the hook 33411 and the card slot 334211 are in a clamped state.

[0148] Specifically, the card slot 334211 is a long slot, the long slot extends along the length direction of the sliding groove 33112, and the hook 33411 can move in the long slot, so that the hook 33411 and the card slot 334211 can be switched between two states of clamping and separation. The setting of the long slot also facilitates the hook 33411 to completely separate from the card slot 334211 after being separated from the card slot 334211 and following the upward movement of the upper cover 332.

[0149] During the process of inserting the sequencing chip 32 into the slot 311 of the gene sequencer 31, the sequencing chip 32 is first partially inserted into the slot 311, and the first end of the hook connector 33421 abuts against the outer shell near the slot 311 of the gene sequencer 31 before the fixing member 3311, and the fixing member 3311 continues to approach the slot 311, and the first end of the hook connector 33421 is squeezed, so that the hook connector 33421 slides into the sliding groove 33112, and the left groove side wall of the slot 334211 retracts, so that the hook 33411 is disengaged from the slot 334211, and the upper cover 332 is no longer subject to the locking force of the locking assembly 334. The upper cover 332 is automatically opened under the action of the reset assembly 333, that is, the second locking connector 3342 contacts the outer shell near the slot 311 of the gene sequencer 31, triggering the locking assembly 334 to unlock. When the hook connector 33421 is no longer squeezed by the gene sequencer 31, the locking spring 3343 will drive the hook connector 33421 to reset. However, the upper cover 332 opens, which drives the hook 33411 to move, so that the hook 33411 is completely separated from the hook connector 33421. Before the locking spring 3343 drives the hook connector 33421 to reset, the locking spring 3343 is in a compressed state, so there is a risk that the hook connector 33421 will fall out of the sliding slot 33112 when it resets. A limiting hole 334213 is provided on the hook connector 33421, and the limiting hole 334213 is not connected to the slot 334211. The locking assembly 334 also includes a limiting member 3345, which is installed in the fixing member 3311 and inserted into the limiting hole 334213. The limiting hole 334213 is a long hole, which extends along the length direction of the sliding slot 33112, so that the limiting member 3345 can have freedom in the limiting hole 334213, so that the sliding of the hook connector 33421 in the sliding slot 33112 is not affected, that is, it does not affect the triggering of the locking assembly 334 to trigger unlocking, but the limiting member 3345 can also prevent the hook connector 33421 from escaping from the sliding slot 33112.

[0150] Preferably, a locking cavity 33113 is provided on the fixing member 3311, and a locking avoidance groove 33124 is provided on the locking positioning member 3312. The locking avoidance groove 33124 and the locking cavity 33113 are arranged vertically opposite to each other. When the hook connecting member 33421 is in a free and uncompressed state, the slot 334211 is connected with the locking cavity 33113, and the hook 33411 passes through the locking avoidance groove 33124 and the locking cavity 33113, and is engaged in the slot 334211.

[0151] Preferably, the contact surface where the catch 33411 is snap-fitted with the slot 334211 is the second arc surface 334212, and the second arc surface 334212 bends from the bottom surface to the top surface, facilitating the snap-fitting of the two. When the catch connecting member 33421 slides into the sliding slot 33112, the catch 33411 will disengage from the second arc surface 334212 for unlocking; when it is necessary to snap the catch 33411 onto the second arc surface 334212, the second locking connecting member 3342 can also be manually pressed so that the catch 33411 is inserted into the slot 334211. After removing the pressing force, the catch 33411 will be snap-fitted into the slot 334211.

[0152] Preferably, two sets of positioning portions 33121 are provided on the above-mentioned locking and positioning member 3312. The two sets of positioning portions 33121 are arranged at intervals along the axial direction of the rotating shaft 338. The sequencing chip 32 is placed between the two sets of positioning portions 33121, and the side surfaces of the sequencing chip 32 are respectively abutted against the two sets of positioning portions 33121. The side surfaces of the sequencing chip 32 are positioned by the positioning portions 33121 on both sides.

[0153] Preferably, the edge of the top surface of the positioning portion 33121 near the sequencing chip 32 is the first arc surface 33122. When the sequencing chip 32 is placed between the two positioning portions 33121, the first arc surface 33122 is provided to prevent scratching of the sequencing chip 32. In addition, it also facilitates the sequencing chip 32 to enter between the two positioning portions 33121.

[0154] Preferably, a first positioning groove 33123 is further provided on the locking and positioning member 3312, and an end positioning protrusion 321 that cooperates with the first positioning groove 33123 is provided on the sequencing chip 32.

[0155] In this embodiment, the first positioning groove 33123 and the end positioning protrusion 321 provided on the sequencing chip 32 cooperate to further ensure the position accuracy of the sequencing chip 32 on the locking and positioning member 3312.

[0156] In this embodiment, the first positioning groove 33123 is located at one end of the positioning portion 33121 close to the rotating shaft 338, and the length of the first positioning groove 33123 is arranged along the axial direction of the rotating shaft 338.

[0157] The end positioning protrusion 321 is inserted into the first positioning groove 33123 for positioning. After the upper cover 332 is closed, the sequencing chip 32 is clamped between the upper cover 332 and the locking and positioning member 3312. Through the cooperation of the end positioning protrusion 321 and the first positioning groove 33123, it is ensured that the position of the sequencing chip 32 will not change during the movement process.

[0158] Preferably, a clamping hole 33111 is formed in the fixing member 3311, and the clamping jaw of the flipping mechanism 34 or the clamping member 22 of the manipulator 2 clamps the fixing member 3311 through the clamping hole 33111.

[0159] When it is necessary to flip the sequencing chip 32, the clamping jaws of the flipping mechanism 34 (the first clamping and positioning member of the first clamping jaw 343 and the second clamping and positioning member 3441 of the second clamping jaw 344) are connected in cooperation with the clamping hole 33111 on the fixing member 3311, and the clamping tooling 330 and the sequencing chip 32 are flipped and clamped through the clamping jaws of the flipping mechanism 34; when it is necessary to move and pre-insert the flipped sequencing chip 32 into the slot 311 of the gene sequencer 31, the clamping member 22 of the manipulator 2 is in cooperation with the clamping hole 33111 of the fixing member 3311, and through the movement of the manipulator 2, the fixing member 3311 and the sequencing chip 32 are driven to move near the slot 311, and the sequencing chip 32 is pre-inserted into the slot 311.

[0160] Preferably, the clamping hole 33111 is arranged on the side wall of the positioning portion 33121, and the clamping holes 33111 are symmetrically arranged on both sides of the sequencing chip 32.

[0161] During the process of inserting the sequencing chip 32 into the slot 311 of the gene sequencer 31, the sequencing chip 32 is first partially inserted into the slot 311, and the first end of the hook connecting member 33421 abuts against the outer shell near the slot 311 of the gene sequencer 31 prior to the fixing member 3311. The fixing member 3311 continues to approach the slot 311, and the first end of the hook connecting member 33421 is squeezed, so that the hook connecting member 33421 slides into the sliding groove 33112, and the left groove side wall of the slot 334211 retracts, so that the hook 33411 is disengaged from the slot 334211, and the upper cover 332 is no longer subjected to the locking force of the locking assembly 334. The upper cover 332 is automatically opened under the action of the reset assembly 333, that is, the second locking connecting member 3342 contacts the outer shell near the slot 311 of the gene sequencer 31 to trigger the unlocking of the locking assembly 334. When the hook connecting member 33421 is no longer squeezed by the gene sequencer 31, the locking spring 3343 drives the hook connecting member 33421 to reset. However, since the opening of the upper cover 332 drives the movement of the hook 33411, the hook 33411 is completely separated from the hook connecting member 33421.

[0162] After the upper cover 332 is automatically opened, the sequencing chip 32 has been pre-inserted into the slot 311. The manipulator 2 can drive the fixing component 331 to move downward, so that the sequencing chip 32 is separated from the fixing component 331. Then, the manipulator 2 drives the fixing piece 3311 to push the sequencing chip 32 to a preset position. When the sequencing chip 32 is inserted into the preset position in place, the gene sequencer 31 will display a successful insertion; if the sequencing chip 32 gets stuck during insertion and fails to reach the preset position, the gene sequencer 31 will not detect the sequencing chip 32, and then the manipulator 2 needs to drive the chip pushing mechanism 23 to push the sequencing chip 32 so that the sequencing chip 32 is inserted into the preset position of the slot 311.

[0163] As Figure 17 shown, at least one slot 311 is provided on the gene sequencer 31, and the slot 311 is for the sequencing chip 32 to be inserted into the gene sequencer 31.

[0164] It should be noted that the respective structures and working principles of the gene sequencer 31 and the sequencing chip 32 are prior arts and will not be elaborated in the present invention.

[0165] As Figure 17 shown, when the sequencing chip 32 is aligned with the slot 311 in the Y and Z directions, one end of the sequencing chip 32 in the X direction (for example Figure 17 the left end of the sequencing chip 32 in Figure 17 ) is pre-inserted into the slot 311, and the manipulator 2 drives the chip pushing mechanism 23 to push the sequencing chip 32 at the other end in the X direction (for example

[0166] the right end of the sequencing chip 32 in

[0167] As Figure 18 and Figure 19As shown, the chip pushing mechanism 23 includes a pushing base 231, a Z-direction adjustment component 232, and a pushing member 233. The pushing base 231 is fixedly disposed on the execution end 21 of the manipulator 2 so that the manipulator 2 drives the chip pushing mechanism 23 to move. The Z-direction adjustment component 232 is disposed on one side of the pushing base 231, for example, on the side of the pushing base 231 away from the execution end 21 of the manipulator 2. The Z-direction adjustment component 232 includes a Z-direction moving member 2321 movable along the Z direction. The pushing member 233 is fixedly disposed on the Z-direction moving member 2321, and the pushing member 233 is located on the side of the Z-direction moving member 2321 away from the pushing base 231, thereby, the pushing member 233 has a Z-direction translational freedom by means of the Z-direction moving member 2321, that is, the pushing member 233 can move in the Z direction relative to the pushing base 231.

[0168] like Figure 18 As shown, the pushing component 233 includes a pushing surface 2331, a first toggle block 2332, and a second toggle block 2333. The pushing surface 2331 is located on the side of the pushing component 233 away from the Z-direction moving component 2321, and the pushing surface 2331 is perpendicular to the X direction. The pushing surface 2331 is used to push the sequencing chip 32 in the X direction. The first toggle block 2332 extends from one end of the pushing surface 2331 in the Z direction (for example, Figure 18 The second moving block 2333 extends from the other end of the pushing surface 2331 in the Z direction (for example, the upper end of the pushing surface 2331) in the X direction and away from the Z-moving component 2321. Figure 18 The lower end of the middle pushing surface 2331 extends along the X direction and away from the Z-direction moving component 2321.

[0169] Thus, a pushing groove is formed on the side of the pushing component 233 away from the Z-moving component 2321 , the pushing surface 2331 serves as the bottom surface of the pushing groove, and the first toggle block 2332 and the second toggle block 2333 serve as the side walls of the pushing groove.

[0170] When the manipulator 2 drives the base 231 to move along the X direction, the pushing surface 2331 can push the sequencing chip 32 to move along the X direction. When the manipulator 2 drives the base 231 to move along the Z direction, the first shifting block 2332 or the second shifting block 2333 can shift the sequencing chip 32 in the Z direction, so that the sequencing chip 32 moves into place after being inserted into the slot 311.

[0171] like Figure 18 As shown, a first toggle surface 23321 is provided on one side of the first toggle block 2332 close to the pushing surface 2331. The first toggle surface 23321 is one of the wall surfaces of the pushing groove, and is used to contact the sequencing chip 32 when the sequencing chip 32 is toggled. The first toggle surface 23321 is a horizontal surface or an inclined surface formed by rotating the horizontal surface along the Y axis.

[0172] like Figure 18 As shown, a second toggle surface 23331 is provided on one side of the second toggle block 2333 close to the pushing surface 2331. The second toggle surface 23331 serves as one of the wall surfaces of the pushing groove, and is used to contact the sequencing chip 32 when the sequencing chip 32 is toggled. The second toggle surface 23331 is a horizontal surface or an inclined surface formed by rotating the horizontal surface along the Y axis.

[0173] like Figure 18 and Figure 19 As shown, the Z-direction adjustment assembly 232 also includes a Z-direction mounting seat 2322, a Z-direction guide component 2323, and a Z-direction elastic component 2324. The Z-direction mounting seat 2322 is arranged on the pushing base 231 so that the execution end 21 of the manipulator 2 drives the Z-direction adjustment assembly 232 to move. The Z-direction guide component 2323 is fixedly arranged on the Z-direction mounting seat 2322 and the Z-direction guide component 2323 extends along the Z direction. Exemplarily, the Z-direction guide component 2323 can be a guide rod. The Z-direction moving component 2321 mentioned above is movably arranged on the Z-direction guide component 2323, so that the Z-direction moving component 2321 can be translated along the Z direction. Z-direction elastic components 2324 are arranged on both sides of the Z-direction moving component 2321 along the Z direction. Exemplarily, the Z-direction elastic component 2324 can be a spring, and the spring can be sleeved on the Z-direction guide component 2323.

[0174] By arranging Z-direction elastic components 2324 on both sides of the Z-direction moving component 2321, the Z-direction moving component 2321 can be kept at a preset position when not subjected to external force, such as the central position of the Z-direction guiding component 2323. When the Z-direction moving component 2321 is moved by external force, the Z-direction guiding component 2323 moves accordingly, thereby extending or compressing, so that when the external force is removed, the Z-direction guiding component 2323 drives the Z-direction moving component 2321 to return to its original position.

[0175] like Figure 19 As shown, the Z-direction mounting seat 2322 includes a first mounting block 23221 and a second mounting block 23222. The second mounting block 23222 is located on one side of the first mounting block 23221 along the Z direction, for example, the second mounting block 23222 is located below the first mounting block 23221. One end ( Figure 19 The upper and middle end of the Z-direction guide member 2323 is fixedly arranged on the first mounting block 23221, and the other end ( Figure 19 The middle and lower end) is fixedly arranged on the second mounting block 23222. In addition, a Z-direction elastic component 2324 is arranged between the first mounting block 23221 and the Z-direction moving component 2321, and between the second mounting block 23222 and the Z-direction moving component 2321.

[0176] likeFigure 18 and Figure 19 As shown in Figure 19 , the chip pushing mechanism 23 further includes an X-direction buffering component 234. The X-direction buffering component 234 is disposed between the pushing base 231 and the Z-direction mounting seat 2322, such that the Z-direction mounting seat 2322 and the pushing base 231 can move relative to each other in the X direction. Thus, when pushing the sequencing chip 32 to move in the X direction, it can provide buffering for the pushing component 233 in the X direction.

[0177] As Figure 18 and Figure 19 shown in Figure 18 and Figure 19 , the X-direction buffering component 234 includes an X-direction moving component 2341, an X-direction guiding component 2342, and an X-direction elastic component 2343. The X-direction moving component 2341 is disposed between the Z-direction mounting seat 2322 and the pushing base 231, and the Z-direction mounting seat 2322 is fixedly disposed on the X-direction moving component 2341. The X-direction guiding component 2342 (such as a guiding rod) extends in the X direction. One end of the X-direction guiding component 2342 is fixedly disposed on the X-direction moving component 2341, and the other end of the X-direction guiding component 2342 is movably disposed on the pushing base 231. The X-direction elastic component 2343 (such as a spring) is disposed between the X-direction moving component 2341 and the pushing base 231.

[0178] By setting the X-direction elastic component 2343, there is a preset distance between the X-direction moving component 2341 and the pushing base 231. When the pushing component 233 is subjected to an external force, the distance between the X-direction moving component 2341 and the pushing base 231 decreases, and the X-direction elastic component 2343 is compressed. When the external force is removed, the X-direction elastic component 2343 elongates, so that the distance between the X-direction moving component 2341 and the pushing base 231 is restored.

[0179] As Figure 19 shown in Figure 19 , in an embodiment, an X-direction channel 2311 penetrating in the X direction is provided on the pushing base 231. One end of the X-direction guiding component 2342 close to the pushing base 231 is movably disposed in the X-direction channel 2311, and one end of the X-direction guiding component 2342 close to the X-direction moving component 2341 is fixedly disposed on the X-direction moving component 2341.

[0180] As Figure 19 and Figure 20 shown in Figure 19 and Figure 20 , in an embodiment, the X-direction guiding component 2342 is a shoulder screw. One end of the shoulder screw close to the X-direction moving component 2341 is threadedly connected to the X-direction moving component 2341, and one end of the shoulder screw close to the pushing base 231 is movably disposed in the X-direction channel 2311.

[0181] The sequencing chip 32 is pre-inserted into the slot 311, and then the execution end 21 of the manipulator 2 drives the chip pushing mechanism 23 to move, so that the pushing component 233 is aligned with the sequencing chip 32 in the Y direction and the Z direction. Then the execution end 21 of the manipulator 2 drives the chip pushing mechanism 23 to move along the X direction, so that the pushing component 233 contacts one end of the sequencing chip 32 and pushes the sequencing chip 32 to move along the X direction. If the sequencing chip 32 is stuck in the Z direction during the movement, the execution end 21 of the manipulator 2 drives the chip pushing mechanism 23 to move in the Z direction, so that the first shifting block 2332 or the second shifting block 2333 contacts the sequencing chip 32 and shifts the sequencing chip 32 in the Z direction, so that the sequencing chip 32 moves into position in the Z direction.

[0182] Figure 21 and Figure 22 A turning mechanism 34 according to a first embodiment of the present invention is shown.

[0183] The flip mechanism 34 includes a flip fixing seat 341 , a flip driving assembly 342 , a first clamping jaw 343 and a second clamping jaw 344 .

[0184] The flip fixing seat 341 is arranged on the frame 1. Figure 21 and Figure 22 In the embodiment, the flip fixing seat 341 is a vertical plate, and the lower end of the vertical plate is used to connect the rack 1. Specifically, the lower end of the vertical plate can be provided with a mounting hole 3411 so as to be connected to the rack 1 by a fastener (such as a screw).

[0185] The flip driving assembly 342 may be disposed on the flip fixing seat 341, that is, the flip fixing seat 341 provides support for the flip driving assembly 342. Figure 21 and Figure 22 In the embodiment, the flip driving assembly 342 can be disposed at the upper end of the flip fixing seat 341 .

[0186] The flip driving assembly 342 is connected to the first clamping jaw 343 and the second clamping jaw 344 , and can drive the first clamping jaw 343 and the second clamping jaw 344 to move and / or rotate synchronously.

[0187] Specifically, the flip driving assembly 342 includes a rotation driving component 3421 and a clamping driving component 3422 which are connected to each other.

[0188] The rotation drive component 3421 is configured to drive the clamping drive component 3422 to rotate around the rotation axis 3423. The rotation axis 3423 may be the axis of the rotation drive component 3421 itself. Figure 21 and Figure 22 In the embodiment, the axis of the rotating driving component 3421 and the axis of the clamping driving component 3422 are collinear. Figure 21and Figure 22 in which, the rotation axis 3423 extends in the horizontal direction.

[0189] The clamping drive member 3422 has a first execution end 34221 and a second execution end 34222. The first jaw 343 is disposed at the first execution end 34221, and the second jaw 344 is disposed at the second execution end 34222. At least one of the first execution end 34221 and the second execution end 34222 is configured to be movable between a clamping position and a relaxation position, so that the first jaw 343 and the second jaw 344 can be switched between a clamping state and a relaxation state.

[0190] Specifically, in one example, the first execution end 34221 is fixedly disposed, and the second execution end 34222 is movable between a clamping position and a relaxation position. Thus, the first jaw 343 cannot move, and the second jaw 344 can move under the drive of the second execution end 34222.

[0191] In another example, both the first execution end 34221 and the second execution end 34222 are movable between a clamping position and a relaxation position. Thus, both the first jaw 343 and the second jaw 344 can move.

[0192] The distance between the first jaw 343 and the second jaw 344 is smaller in the clamping state than in the relaxation state, so that the clamping tooling 330 holding the sequencing chip 32 can be clamped between the first jaw 343 and the second jaw 344.

[0193] As Figure 21 shown, a clamping area is formed between the first jaw 343 and the second jaw 344, and the clamped clamping tooling 330 is located within the clamping area. Specifically, the first jaw 343 is located on one side of the clamping tooling 330, and the second jaw 344 is located on the other side of the clamping tooling 330, that is, the first jaw 343 and the second jaw 344 can clamp the opposite sides of the clamping tooling 330 from opposite directions.

[0194] As Figure 21 shown, a clamping hole 33111 is provided on the side wall of one side of the fixing member 3311 of the clamping tooling 330, and a clamping hole 33111 is also provided on the side wall of the other side of the clamping tooling 330. The clamping hole 33111 can be a through hole or a blind hole.

[0195] A first clamping positioning member (not shown) is provided on the side of the first jaw 343 facing the clamping area. The shape and size of the first clamping positioning member correspond to the shape and size of the clamping hole 33111. When the first jaw 343 is in the clamping state, the first clamping positioning member is inserted into the clamping hole 33111.

[0196] On one side of the second jaw 344 facing the clamping area, a second clamping and positioning member 3441 is provided (see Figure 23 ). The shape and size of the second clamping and positioning member 3441 correspond to the shape and size of the clamping hole 33111. When the second jaw 344 is in the clamping state, the second clamping and positioning member 3441 is inserted into the clamping hole 33111.

[0197] In summary, when the flipping mechanism 34 according to the first embodiment of the present invention clamps the clamping tooling 330, the first clamping and positioning member of the first jaw 343 is inserted into the clamping hole 33111 of the clamping tooling 330, and the second clamping and positioning member 3441 of the second jaw 344 is inserted into the clamping hole 33111 on the other side of the clamping tooling 330. Thus, the positioning accuracy when clamping the clamping tooling 330 is improved through the mechanical cooperation between the clamping and positioning member and the clamping hole 33111.

[0198] Optionally, the first clamping and positioning member can be detachably provided on the first jaw 343 to facilitate replacing the worn first clamping and positioning member or replacing the first clamping and positioning member with different shapes and / or sizes. For similar reasons, the second clamping and positioning member 3441 can also be detachably provided on the second jaw 344.

[0199] Optionally, the first clamping and positioning member is selected from one of a positioning protrusion and a positioning pin. The positioning protrusion can be a semi-circular protrusion. The positioning pin can be a cylindrical positioning pin or a conical positioning pin, and the shape of the clamping hole 33111 is adapted to the outer shape of the first clamping and positioning member. For example, when the positioning pin is a conical positioning pin, the clamping hole 33111 is a conical hole. For similar reasons, the second clamping and positioning member 3441 can be selected from one of a positioning protrusion and a positioning pin.

[0200] Optionally, there can be multiple first clamping and positioning members, such as two, three, etc. By providing multiple first clamping and positioning members, the positioning accuracy when clamping the clamping tooling 330 can be further improved. For similar reasons, there can also be multiple second clamping and positioning members 3441.

[0201] In Figure 21 and Figure 22 , the rotation driving member 3421 and the clamping driving member 3422 are two independent components. Specifically, the rotation driving member 3421 can be a rotary cylinder or a rotary electric cylinder. The clamping driving member 3422 can be a finger cylinder or a finger electric cylinder.

[0202] The rotation driving member 3421 and the clamping driving member 3422 can be connected to each other through a connecting component 345.

[0203] Exemplarily, the connecting component 345 includes a first flipping connecting piece 3451 and a second flipping connecting piece 3452. The first flipping connecting piece 3451 is connected to the rotating seat of the rotating flipping driving component 342. The second flipping connecting piece 3452 is connected to the first flipping connecting piece 3451, and the second flipping connecting piece 3452 is connected to the outer side wall of the clamping driving part 3422. Thus, when the rotating seat of the rotating driving part 3421 rotates, the first flipping connecting piece 3451 rotates accordingly and drives the second flipping connecting piece 3452 to rotate synchronously. Finally, the clamping driving part 3422 also rotates synchronously.

[0204] As Figure 22 shown, the flipping mechanism 34 further includes a sensor component 346, and the sensor component 346 is configured to measure the angle of rotation of the clamping driving part 3422. After the sensor component 346 detects that the clamping driving part 3422 has rotated a preset angle (such as 45 degrees, 90 degrees, 180 degrees, etc.), the rotational movement of the rotating driving part 3421 is stopped.

[0205] Exemplarily, the sensor component 346 includes a groove-type optoelectronic switch 3461 and a switch baffle 3462. The groove-type optoelectronic switch 3461 is fixedly arranged relative to the rotating driving part 3421. For example, the groove-type optoelectronic switch 3461 is fixed on the flipping fixed seat 341 through a switch mounting seat 3463. The switch baffle 3462 is arranged on the connecting component 345 (such as the first flipping connecting piece 3451). When the connecting component 345 rotates under the drive of the rotating driving part 3421, the switch baffle 3462 follows the connecting component 345 to perform a rotational movement, and the movement track of the switch baffle 3462 passes through the groove-type optoelectronic switch 3461. Thus, the groove-type optoelectronic switch 3461 can detect that the connecting component 345 has rotated a preset angle, that is, the clamping driving part 3422 has rotated a preset angle.

[0206] Figure 23 The perspective view of the flipping mechanism 34 according to the second embodiment of the present invention is shown. Different from the first embodiment, the flipping driving component 342 is a rotating jaw, that is, the rotating driving part 3421 and the clamping driving part 3422 are integrated in one component. The rotating jaw can not only drive the first jaw 343 and the second jaw 344 to move, but also drive the first jaw 343 and the second jaw 344 to rotate synchronously.

[0207] The specific process of sequencing the product to be sequenced is as follows:

[0208] Step 1: Manually assemble the sequencing chip 32 and the sample loading clamping mechanism 33 together and place them on the normal temperature storage mechanism 51: The first positioning groove 33123 cooperates with the end positioning protrusion 321, and the positioning part 33121 positions the sequencing chip 32, so that the sequencing chip 32 is clamped on the clamping tooling 330. The hook 33411 is clamped in the card slot 334211, and both the torsion spring 3332 and the locking spring 3343 are in a compressed state. Then, place the sequencing chip 32 and the clamping tooling 330 in the installation groove 3310 with the sample loading port 322 facing upward. Then, place the sample loading seat 337 on the clamping base 336 so that the positioning wall 3364 cooperates with the opening positioning card slot 3373, and the side positioning protrusion 323 of the sequencing chip 32 cooperates with the opening card slot 3371 of the sample loading seat 337;

[0209] Step 2: After the clamping part 22 of the manipulator 2 places the sample loading clamping mechanism 33 clamping the sequencing chip 32 on the calibration device 8 for position calibration, then transport it to the transfer module 41 of the library preparation instrument 4:

[0210] Step 3: The transfer module 41 transports the sample loading clamping mechanism 33 and the sequencing chip 32 into the library preparation instrument 4. The library preparation instrument 4 injects the product to be sequenced into the sample loading port 322 through the sample loading channel 3372. After the sample loading is completed, the built-in gripper of the library preparation instrument 4 takes away the sample loading seat 337. The sample loading seat 337 is recycled and sorted by the experimenter after the experiment is received. The clamping tooling 330, the clamping base 336, and the sequencing chip 32 are output from the library preparation instrument 4 by the transfer module 41;

[0211] Step 4: The clamping part 22 of the manipulator 2 grabs the clamping base 336 to transport the clamping tooling 330, the clamping base 336, and the sequencing chip 32 as a whole to the calibration device 8 for position calibration, and then the manipulator 2 transports the calibrated clamping tooling 330, the clamping base 336, and the sequencing chip 32 as a whole to the flipping mechanism 34;

[0212] Step 5: The flipping mechanism 34 grabs the clamping tooling 330 with the sequencing chip 32, separates the clamping tooling 330 from the clamping base 336. The clamping tooling 330 with the sequencing chip 32 is flipped 180° by the flipping mechanism 34. The manipulator 2 grabs the clamping base 336 and can grab the clamping base 336 to the calibration device 8 or directly to the normal temperature storage mechanism 51;

[0213] Step 6: The clamping member 22 is clamped onto the clamping hole 33111 of the flipped clamping tooling 330, and the flipped clamping tooling 330 is transported to the slot 311 of the gene sequencer 31. The execution end 21 drives the clamping member 22 and the clamping tooling 330 to move in the X direction to pre-insert the sequencing chip 32 into the slot 311. When the hook connecting member 33421 contacts the outer shell around the slot 311, the hook connecting member 33421 is triggered to unlock from the hook 33411, and the upper cover 332 opens the installation slot 3310 under the action of the reset assembly 333. The execution end 21 drives the clamping member 22 to move downward in the Y direction, so that the sequencing chip 32 is separated from the clamping tooling 330. Then, the execution end 21 drives the clamping member 22 to move in the X direction, so that the outer surface of the fixing member 3311 contacts one end of the sequencing chip 32 outside the slot 311, and then pushes the sequencing chip 32 to the preset position in the slot 311; when the sequencing chip 32 gets stuck, the execution end 21 rotates along the axis in the Z direction, so that the chip pushing mechanism 23 faces the slot 311, and then inserts the stuck sequencing chip 32 into the preset position in the slot 311;

[0214] Step 7: The clamping member 22 of the manipulator 2 sends the clamping tooling 330 separated from the sequencing chip 32 back to the storage device 5.

[0215] As Figures 24 - 29 shown, the low-temperature storage mechanism 52 includes an anti-condensation component 521. The anti-condensation component 521 includes a storage mounting base 5211, a gland component 5212, and a slow-elastic component 5213. The storage mounting base 5211 is provided with a mounting surface 521113. The gland component 5212 is mounted on the mounting surface 521113. The first end of the slow-elastic component 5213 is mounted on the mounting surface 521113. The gland component 5212 has a first state and a second state. When the gland component 5212 is in the first state, both the gland component 5212 and the second end of the slow-elastic component 5213 abut against the sealing surface of the consumable cartridge 6; when the gland component 5212 is in the second state, the gland component 5212 is away from the sealing surface of the consumable cartridge 6, and the second end of the slow-elastic component 5213 extends beyond the gland component 5212 and abuts against the sealing surface of the consumable cartridge 6. When the gland component 5212 is in the first state, the gland component 5212 abuts against the sealing surface of the consumable cartridge 6, which can prevent condensed water from entering the consumable cartridge 6 from the sealing surface; when the gland component 5212 is in the second state, the gland component 5212 is away from the sealing surface of the consumable cartridge 6, but the second end of the slow-elastic component 5213 still abuts against the sealing surface of the consumable cartridge 6, preventing the consumable cartridge 6 from moving with the gland component 5212, preventing damage to the consumable cartridge 6 and the refrigerated items on the consumable cartridge 6, extending the service life of the consumable cartridge 6, and ensuring the safety of low-temperature storage.

[0216] In this embodiment, the refrigerated object enters the consumable cartridge 6 from the opening of the consumable cartridge 6, and the plane where the opening of the consumable cartridge 6 is located is the sealing surface of the consumable cartridge 6.

[0217] Further, the elastic member 5213 includes an elastic element 52131 and an elastic component 52133. One end of the elastic component 52133 is connected to the mounting surface 521113, and the other end of the elastic component 52133 is connected to the elastic element 52131. When the pressing cover component 5212 is in the first state, the elastic element 52131 abuts against the sealing surface of the consumable cartridge 6; when the pressing cover component 5212 is in the second state, the elastic element 52131 extends beyond the pressing cover component 5212 and abuts against the sealing surface of the consumable cartridge 6. When the pressing cover component 5212 is in the first state, the elastic component 52133 is in a compressed state; when the pressing cover component 5212 is in the second state, the elastic element 52131 still abuts against the sealing surface of the consumable cartridge 6 under the action of the elastic force of the elastic component 52133. At this time, the pressing cover component 5212 has moved away from the sealing surface of the consumable cartridge 6, preventing the consumable cartridge 6 from moving with the pressing cover component 5212, preventing damage to the consumable cartridge 6 and the refrigerated object on the consumable cartridge 6, extending the service life of the consumable cartridge 6, and ensuring the safety of low-temperature storage.

[0218] Preferably, the elastic component 52133 can be a spring.

[0219] Such as Figure 24 and Figure 25 As shown, the anti-condensation water assembly 521 further includes a fastener 5215. The pressing cover component 5212 includes a pressing plate 52121. The pressing plate 52121 is connected to the mounting surface 521113 through the fastener 5215, and the pressing plate 52121 can move away from or press on the sealing surface of the consumable cartridge 6.

[0220] Further, the pressing cover component 5212 further includes an elastic pad 52122. The elastic pad 52122 is provided on the pressing plate 52121, and the elastic pad 52122 can move away from or abut against the sealing surface of the consumable cartridge 6. The setting of the elastic pad 52122 makes the contact between the pressing plate 52121 and the sealing surface of the consumable cartridge 6 a soft contact, preventing damage to the consumable cartridge 6, and the elastic pad 52122 has a better sealing effect on the sealing surface of the consumable cartridge 6, so that the anti-condensation water effect is better. At the same time, the elastic pad 52122 has a certain heat insulation effect, so that the temperature on the surface of the consumable cartridge 6 is maintained at a low level and does not change too much, thereby ensuring the refrigeration effect of the low-temperature storage mechanism 52.

[0221] Further, the anti-condensation water assembly 521 further includes a buffer member 5214. One end of the buffer member 5214 is connected to the mounting surface 521113, and the other end is connected to the pressing plate 52121. The setting of the buffer member 5214 plays a buffering role between the pressing cover component 5212 and the consumable cartridge 6, preventing damage to the consumable cartridge 6.

[0222] Specifically, the buffer member 5214 can be a spring.

[0223] Furthermore, the gland member 5212 is provided with an avoidance groove for avoiding the slow-acting elastic member 52131.

[0224] Specifically, a first avoidance groove 521211 is formed on the pressing plate 52121, and a second avoidance groove 521221 is formed on the elastic pad 52122. The first avoidance groove 521211 and the second avoidance groove 521221 are arranged opposite to each other to jointly form an avoidance groove, so as to avoid interference with the movement of the slow-acting elastic member 52131.

[0225] Furthermore, the number of the slow-acting elastic members 5213 is multiple groups. The multiple groups of slow-acting elastic members 5213 are arranged at intervals along the mounting surface 521113, and the avoidance grooves are arranged in one-to-one correspondence with the slow-acting elastic members 5213.

[0226] As Figures 26 - 29 shown, the slow-acting elastic member 5213 further includes a slow-acting fixing seat 52132. The slow-acting fixing seat 52132 is installed on the mounting surface 521113. A guiding cavity is formed by surrounding between the slow-acting fixing seat 52132 and the mounting surface 521113. The elastic member 52133 is arranged in the guiding cavity, and the slow-acting elastic member 52131 is guided by the guiding cavity. The setting of the guiding cavity can ensure the movement accuracy of the slow-acting elastic member 52131 under the elastic force of the elastic member 52133.

[0227] Furthermore, the slow-acting elastic member 52131 includes a guiding portion 521311 and a pressing portion 521312. The guiding portion 521311 protrudes from the outer side surface of the pressing portion 521312. The guiding portion 521311 is movably arranged in the guiding cavity. The pressing portion 521312 passes through the slow-acting fixing seat 52132, and can extend beyond the gland member 5212 and can abut against the sealing surface of the consumable cartridge 6. Such a setting can prevent the slow-acting elastic member 52131 from coming out of the guiding cavity.

[0228] Furthermore, a first guiding groove 521112 is formed on the mounting surface 521113, and a second guiding groove 521322 is formed on the slow-acting fixing seat 52132. When the slow-acting fixing seat 52132 is installed on the mounting surface 521113, the first guiding groove 521112 and the second guiding groove 521322 are arranged opposite to each other and jointly surround to form a guiding cavity, and the guiding portion 521311 is movably arranged in the first guiding groove 521112 and the second guiding groove 521322.

[0229] Furthermore, a movable groove 521321 is formed on the slow-acting fixing seat 52132. The movable groove 521321 is communicated with the second guiding groove 521322, and the pressing portion 521312 passes through the slow-acting fixing seat 52132 through the movable groove 521321.

[0230] Further, a fastening groove 521323 is formed on the slow-elastic fixing seat 52132, and the slow-elastic fixing seat 52132 can be fixedly connected to the storage mounting seat 5211 through the fastening groove 521323.

[0231] As Figure 26 , Figure 27 and Figure 29 shown, the slow-elastic fixing seat 52132 includes a fixing portion 521324 and a protruding portion 521325. The fixing portion 521324 is fixedly mounted on the mounting surface 521113, and the protruding portion 521325 protrudes from the fixing portion 521324 toward the direction close to the consumable cartridge 6. The pressing portion 521312 passes through the protruding portion 521325. Specifically, the movable groove 521321 is formed on the protruding portion 521325, and the fastening groove 521323 is formed on the fixing portion 521324.

[0232] Further, a fixing groove 521111 is formed on the storage mounting seat 5211, and the fixing portion 521324 is mounted in the fixing groove 521111. Specifically, the fixing groove 521111 is formed on the mounting surface 521113, and the fixing portion 521324 is placed in the fixing groove 521111 to play a limiting role. A connecting groove is formed on the bottom groove wall of the fixing groove 521111. When the fixing portion 521324 is placed in the fixing groove 521111, the connecting groove and the fastening groove 521323 are aligned and communicated, and the fastener 5215 connects the storage mounting seat 5211 and the slow-elastic fixing seat 52132 through the connecting groove and the fastening groove 521323.

[0233] As Figures 30 - 32As shown in the figure, this embodiment also provides a low-temperature storage mechanism 52, which includes an anti-condensation water component 521, a refrigeration component 523, and a storage driving component 522. The refrigeration component 523 includes a support frame 5231 and a refrigeration element 5232. A consumable cartridge 6 is placed on the support frame 5231, and the refrigeration element 5232 cools the consumable cartridge 6. The storage driving component 522 drives the storage mounting base 5211 to move up and down relative to the support frame 5231. When the storage driving component 522 drives the storage mounting base 5211 to move downward, the pressing cover member 5212 and the elastic buffer member 5213 move downward following the storage mounting base 5211. The second ends of both the pressing cover member 5212 and the elastic buffer member 5213 abut against the sealing surface of the consumable cartridge 6, that is, the pressing cover member 5212 is in the first state, which can prevent condensed water from entering the consumable cartridge 6 from the sealing surface. When the storage driving component 522 drives the storage mounting base 5211 to move upward, the pressing cover member 5212 moves upward following the storage mounting base 5211, causing the pressing cover member 5212 to move away from the sealing surface of the consumable cartridge 6. However, the second end of the elastic buffer member 5213 extends beyond the pressing cover member 5212 and still abuts against the sealing surface of the consumable cartridge 6, that is, the pressing cover member 5212 is in the second state, preventing the consumable cartridge 6 from moving following the pressing cover member 5212, preventing damage to the consumable cartridge 6 and the refrigerated items on the consumable cartridge 6, extending the service life of the consumable cartridge 6, and ensuring the safety of low-temperature storage.

[0234] Of course, in other embodiments, the storage driving component 522 can also drive the storage mounting base 5211 to rotate or translate on a horizontal plane. The movement form of the storage mounting base 5211 is not limited, as long as it can cover or move away from the consumable cartridge 6 with the anti-condensation water component 521.

[0235] In this embodiment, the low-temperature storage mechanism 52 further includes a housing 524, and the housing 524 covers the anti-condensation water component 521, the storage driving component 522, and the refrigeration component 523.

[0236] Furthermore, the storage driving component 522 includes a storage driving member 5222 and a storage driving plate 5221. The storage driving member 5222 is fixedly installed on the housing 524. The storage driving member 5222 drives the storage driving plate 5221 to move up and down relative to the support frame 5231, and the anti-condensation water component 521 is installed on the storage driving plate 5221. Specifically, the storage mounting base 5211 is fixedly installed on the storage driving plate 5221.

[0237] Further, the storage mounting base 5211 includes a mounting portion 52111 and a connecting portion 52112. The mounting portion 52111 and the connecting portion 52112 are integrally formed, and the connecting portion 52112 is located at the end of the mounting portion 52111. The mounting surface 521113 is provided on the mounting portion 52111, and the connecting portion 52112 is fixedly mounted on the storage drive board 5221. The storage drive member 5222 drives the storage drive board 5221 to descend, and the storage drive board 5221 drives the storage mounting base 5211, the gland member 5212 and the buffer elastic member 5213 to descend, so that the elastic pad 52122 in the gland member 5212 and the buffer elastic member 52131 in the buffer elastic member 5213 both press on the sealing surface of the consumable cartridge 6. During this process, the elastic member 52133 is in a compressed state; the storage drive member 5222 drives the storage drive board 5221 to ascend, and then drives the storage mounting base 5211 and the gland member 5212 to ascend, so that the elastic pad 52122 of the gland member 5212 is away from the sealing surface of the consumable cartridge 6, facilitating the taking and placing of the refrigerated items on the consumable cartridge 6. During this process, since the elastic member 52133 is in a compressed state, the buffer elastic member 52131 still presses tightly on the sealing surface of the consumable cartridge 6, preventing the consumable cartridge 6 from moving along with the gland member 5212, preventing damage to the consumable cartridge 6 and the refrigerated items on the consumable cartridge 6, prolonging the service life of the consumable cartridge 6, and ensuring the safety of low-temperature storage.

[0238] Further, the storage drive assembly 522 further includes a mounting board 5223. The mounting board 5223 is fixedly mounted on the inner wall surface of the housing 524, and the storage drive member 5222 is mounted on the mounting board 5223.

[0239] Further, the storage drive assembly 522 further includes a connecting block 5224. The output end of the storage drive member 5222 is connected to the connecting block 5224, and the storage drive board 5221 is mounted on the connecting block 5224.

[0240] In this embodiment, the number of the support frames 5231 can be multiple, and the multiple support frames 5231 can be arranged in rows and columns to facilitate the low-temperature storage of more consumable cartridges 6. In this embodiment, the specific number of the support frames 5231 in each row and each column is not limited and can be set according to the actual situation.

[0241] In this embodiment, the number of the refrigerating members 5232 is not limited. The refrigerating members 5232 can refrigerate all the consumable cartridges 6, or the refrigerating members 5232 can be arranged in one-to-one correspondence with the consumable cartridges 6, as long as a good refrigeration effect can be achieved.

[0242] Although the present invention has been described in detail above with general descriptions, specific embodiments and experiments, modifications or improvements can be made to it based on the present invention, which are obvious to those skilled in the art. Therefore, these modifications or improvements made without departing from the spirit of the present invention all fall within the scope of protection required by the present invention.

Claims

1. An all-in-one automatic machine for NGS library construction hybridization sequencing interpretation, which is used for loading samples and sequencing on a sequencing chip (32), and is characterized in that, It includes a frame (1), a manipulator (2), a sequencing device (3) and a library preparation instrument (4) provided on the frame (1). The sequencing device (3) includes a gene sequencer (31), a sample loading clamping mechanism (33) and a flipping mechanism (34). The library preparation instrument (4) can load samples for the sequencing chip (32). A slot (311) for inserting the sequencing chip (32) is provided on the gene sequencer (31). The sample loading clamping mechanism (33) includes a clamping base (336) and a clamping tooling (330). A second positioning groove (3361) is provided on the clamping base (336). The clamping tooling (330) is placed in the second positioning groove (3361), and the clamping tooling (330) is used to clamp the sequencing chip (32). The flipping mechanism (34) can flip the clamping tooling (330) to drive the sequenced chip (32) after sample loading to flip. The manipulator (2) includes an execution end (21) and a clamping member (22). The clamping member (22) is provided on the execution end (21). The clamping member (22) can clamp the clamping base (336) or the clamping tooling (330). The execution end (21) can move between the library preparation instrument (4), the flipping mechanism (34) and the gene sequencer (31) so that the sequencing chip (32) is loaded with samples, flipped and then inserted into a preset position of the slot (311).

2. The fully automatic integrated machine for NGS library construction, hybridization sequencing and interpretation according to claim 1, wherein The clamping tooling (330) includes: A fixing component (331), which includes a fixing member (3311) and a locking and positioning member (3312). An installation groove (3310) is provided on the fixing member (3311). The locking and positioning member (3312) is arranged in the installation groove (3310). A positioning portion (33121) for positioning the sequencing chip (32) is provided on the locking and positioning member (3312). An upper cover (332), one end of which is rotatably connected to the fixing member (3311) and is used to switch between opening and closing the installation groove (3310). A reset component (333), which is arranged between the upper cover (332) and the fixing component (331), and the reset component (333) is used to automatically open the unlocked upper cover (332). A locking component (334), which is arranged between the upper cover (332) and the fixing component (331), and the locking component (334) is used to lock the closed upper cover (332). When the upper cover (332) is closed, the sequencing chip (32) is clamped between the locking and positioning member (3312) and the upper cover (332).

3. The fully automatic integrated machine for NGS library construction hybridization sequencing interpretation according to claim 2, wherein The locking component (334) includes: A first locking connecting piece (3341), which is arranged on the upper cover (332). A second locking connector (3342) is provided on the fixed assembly (331). The first locking connector (3341) and the second locking connector (3342) can be latched or opened. When the second locking connector (3342) contacts the gene sequencer (31), the first locking connector (3341) and the second locking connector (3342) are opened.

4. The fully automatic integrated machine for NGS library construction, hybridization sequencing and interpretation according to claim 3, characterized in that, The first locking connector (3341) includes a hook (33411), and one end of the hook (33411) is connected to the upper cover (332); The second locking connector (3342) includes a hook connector (33421). A sliding slot (33112) is formed in the fixing member (3311) below the locking positioning member (3312), and one end of the hook connector (33421) is slidably disposed in the sliding slot (33112); A card slot (334211) is formed in the hook connector (33421). When the second locking connector (3342) contacts the gene sequencer (31), one end of the hook connector (33421) slides in the sliding slot (33112) so that the other end of the hook (33411) disengages from the card slot (334211).

5. The fully automatic integrated machine for NGS library construction, hybridization sequencing and interpretation according to claim 4, wherein The locking assembly (334) further includes a locking spring (3343). The locking spring (3343) is used to keep the hook (33411) and the card slot (334211) in a latched state. One end of the hook connector (33421) is connected to one end of the locking spring (3343), and the other end of the locking spring (3343) is connected to the groove wall of the sliding slot (33112).

6. The fully automatic integrated machine for NGS library construction, hybridization sequencing and interpretation according to claim 2, wherein The upper cover (332) and the fixing member (3311) are rotatably connected by a rotating shaft (338). The reset assembly (333) includes: A torsion spring mounting member (3331) is rotatably mounted on the rotating shaft (338), and the torsion spring mounting member (3331) is connected to the upper cover (332); A torsion spring (3332) is sleeved on the rotating shaft (338) and mounted on the torsion spring mounting member (3331).

7. The fully automatic integrated machine for NGS library construction, hybridization sequencing and interpretation according to claim 2, wherein The sample loading clamping mechanism (33) further includes a sample loading seat (337). A sample loading port (322) is provided on the sequencing chip (32). The sample loading seat (337) is located on one side of the sample loading port (322), and the clamping tooling (330) is located on the opposite side of the sample loading seat (337); A side positioning protrusion (323) is provided on the side wall of one end of the sequencing chip (32) extending out of the clamping tooling (330); The sample loading seat (337) is placed on the clamping base (336). An open card slot (3371) is provided on the sample loading seat (337), and the side positioning protrusion (323) is clamped in the open card slot (3371).

8. The fully automatic integrated machine for NGS library construction hybridization sequencing interpretation according to claim 1, characterized in that, The manipulator (2) further comprises a chip pushing mechanism (23), the chip pushing mechanism (23) being connected to the execution end (21) and being used for pushing the stuck sequencing chip (32) to a preset position of the slot (311), the chip pushing mechanism (23) comprising: Pushing the base (231); A Z-direction adjustment component (232), the Z-direction adjustment component (232) being arranged on one side of the pushing base (231), the Z-direction adjustment component (232) comprising a Z-direction moving component (2321) movable along the Z direction; and A pushing component (233), wherein the pushing component (233) is fixedly arranged on a side of the Z-direction moving component (2321) away from the pushing base (231), and the pushing component (233) comprises: A pushing surface (2331), the pushing surface (2331) being located on a side of the pushing component (233) away from the Z-direction moving component (2321), and the pushing surface (2331) being perpendicular to the X-direction; a first toggle block (2332), the first toggle block (2332) extending from one end of the pushing surface (2331) in the Z direction along the X direction and away from the Z-direction moving component (2321); and A second toggle block (2333), the second toggle block (2333) extends from the other end of the pushing surface (2331) in the Z direction along the X direction and away from the Z-direction moving component (2321).

9. The fully automatic integrated machine for NGS library construction, hybridization sequencing and interpretation according to claim 1, wherein The turning mechanism (34) comprises: A flip drive assembly (342), the flip drive assembly (342) comprising a rotation drive component (3421) and a clamping drive component (3422) connected to each other, the rotation drive component (3421) being configured to drive the clamping drive component (3422) to rotate around a rotation axis (3423), the clamping drive component (3422) having a first execution end (34221) and a second execution end (34222), at least one of the first execution end (34221) and the second execution end (34222) being configured to be movable between a clamping position and a relaxing position; A first clamping jaw (343), wherein the first clamping jaw (343) is disposed at the first execution end (34221); and a second clamping jaw (344), wherein the second clamping jaw (344) is disposed at the second execution end (34222), A clamping area is formed between the first clamping jaw (343) and the second clamping jaw (344), a first clamping positioning piece is provided on the side of the first clamping jaw (343) facing the clamping area, and a second clamping positioning piece (3441) is provided on the side of the second clamping jaw (344) facing the clamping area.

10. The fully automatic integrated machine for NGS library construction, hybridization sequencing and interpretation according to claim 1, wherein The NGS library construction, hybridization, sequencing and interpretation fully automatic integrated machine also includes a low-temperature storage mechanism (52), and the low-temperature storage mechanism (52) includes: Anti-condensation water component (521), which includes a storage mounting base (5211), a gland component (5212) and a slow-elastic component (5213). An installation surface (521113) is provided on the storage mounting base (5211). The gland component (5212) is installed on the installation surface (521113). The first end of the slow-elastic component (5213) is installed on the installation surface (521113). The gland component (5212) has a first state and a second state. When the gland component (5212) is in the first state, both the gland component (5212) and the second end of the slow-elastic component (5213) abut against the sealing surface of the consumable cartridge (6). When the gland component (5212) is in the second state, the gland component (5212) is away from the sealing surface of the consumable cartridge (6), and the second end of the slow-elastic component (5213) extends beyond the gland component (5212) and abuts against the sealing surface of the consumable cartridge (6); Refrigeration component (523), which includes a support frame (5231) and a refrigeration element (5232). The consumable cartridge (6) is placed on the support frame (5231), and the refrigeration element (5232) refrigerates the consumable cartridge (6); Storage drive component (522), which drives the storage mounting base (5211) to move up and down relative to the support frame (5231).

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