Nucleic acid extraction device and nucleic acid extraction method

Abstract

The invention provides a nucleic acid extraction device and a nucleic acid extraction method, the nucleic acid extraction device is used for carrying out nucleic acid extraction on a large-volume sample, the device comprises a biological sample processing device bearing assembly used for bearing a biological sample processing device, and the biological sample processing device comprises a plurality of chambers and at least one cracking chamber; the magnetic particle transfer assembly drives the magnetic rod and the magnetic rod sleeve to move, so that the magnetic particles are transferred among the plurality of cavities; the auxiliary magnetic attraction assembly drives the magnetism gathering magnet to move, so that the magnetic particles are gathered at a preset part of at least one cavity of the multiple cavities; and the controller is used for controlling the magnetic bar and the magnetic bar sleeve to move to a preset part so as to transfer the magnetic particles. According to the nucleic acid extraction device, the magnetic particles in the cracking cavity are subjected to auxiliary aggregation, so that the magnetic particles are aggregated in a preset part of the cracking cavity, and the transfer efficiency of the magnetic particles from a large-volume cracking solution to an eluent which is less than hundreds of times of the large-volume cracking solution is improved.

Description

[0001] Cross - Reference to Related Applications

[0002] This application claims the priority of Chinese Patent Application No. CN202311815491.0, titled "Nucleic Acid Extraction Device and Nucleic Acid Extraction Method", filed on December 27, 2023. The content of the above application is incorporated herein by reference. Technical Field

[0003] The present invention relates to the technical field of nucleic acid extraction, and particularly to a nucleic acid extraction device and a nucleic acid extraction method. Background Art

[0004] An automated nucleic acid extractor is an instrument that uses a supporting nucleic acid extraction reagent to automatically complete the nucleic acid extraction work of samples. It is widely used in various fields such as disease control centers, clinical disease diagnosis, blood transfusion safety, forensic identification, environmental microorganism detection, food safety detection, animal husbandry, and molecular biology research.

[0005] Existing automated nucleic acid extractors mostly use 96-well deep plates as reaction carriers to process small-volume samples of 200 - 300 μl. Currently, there is a need to extract nucleic acids from larger-volume samples, such as extracting nucleic acids from samples with a volume of 1 ml or even 3 ml, for example, extracting free nucleic acids.

[0006] The traditional nucleic acid extraction steps by the magnetic particle method include: lysis - binding - washing - elution. The extraction methods include the magnetic rod method and the pipetting method. Among them, the magnetic rod method, also called the magnetic bar method, realizes nucleic acid extraction by fixing the liquid and transferring magnetic particles; the pipetting method realizes nucleic acid extraction by fixing magnetic particles and transferring the liquid.

[0007] Different steps of nucleic acid extraction from samples require different proportions of reaction reagents. For example, a 3-ml sample may require about twice the amount of lysis buffer, so the reaction system during the lysis process can reach 9 ml. The above two traditional nucleic acid extraction methods by the magnetic particle method are suitable for nucleic acid extraction of small-volume samples. However, for a large-volume reaction system with a larger lysis chamber volume and more liquid placed therein, problems such as extraction speed, the volume of self-developed reaction carriers, magnetic aggregation efficiency, and magnetic particle loss rate also need to be considered.

[0008] The present invention aims to solve various problems in nucleic acid extraction from large-volume samples. Summary of the Invention

[0009] To solve at least one of the above technical problems, the present invention provides a nucleic acid extraction device and a nucleic acid extraction method.

[0010] The first aspect of the present invention provides a nucleic acid extraction device for extracting nucleic acids from large-volume samples, which includes:

[0011] A carrier assembly for a biological sample processing device, which is used to carry the biological sample processing device. The biological sample processing device includes a plurality of chambers, and at least includes a lysis chamber;

[0012] A magnetic particle transfer assembly, which is used to drive the magnetic rod and the magnetic rod sleeve to move, so that the magnetic particles are transferred between the plurality of chambers;

[0013] An auxiliary magnetic attraction assembly, which is used to drive the magnetic aggregation magnet to move, so that the magnetic particles are aggregated at a preset position in at least one of the plurality of chambers;

[0014] A controller, which is used to control the magnetic rod and the magnetic rod sleeve to move to a preset position for magnetic particle transfer.

[0015] In one embodiment, the lysis chamber is used to store the lysis reagent and provide a reaction site for the lysis of biological samples and the binding of nucleic acids and magnetic particles.

[0016] In one embodiment, the nucleic acid is free nucleic acid.

[0017] In one embodiment, the preset position is located at the bottom of the chamber.

[0018] In one embodiment, the preset position is located at the bottom of the lysis chamber.

[0019] In one embodiment, the magnetic rod is used to be inserted into the magnetic rod sleeve, so that the magnetic particles are adsorbed on the outer surface of the bottom of the magnetic rod sleeve.

[0020] In one embodiment, the chambers of the biological sample processing device further include at least one washing chamber, one magnetic rod sleeve storage chamber, one magnetic particle storage chamber and one elution chamber, and the magnetic rod sleeve storage chamber pre-stores the magnetic rod sleeve.

[0021] In one embodiment, the diameter of the part of the magnetic rod sleeve in contact with the liquid in the chamber is 5.5 mm - 6.5 mm.

[0022] In one embodiment, the opening cross-section of the lysis chamber is waist-shaped.

[0023] In one embodiment, the cross-sectional width of the lysis chamber is 1 mm - 3 mm greater than the diameter of the part of the magnetic rod sleeve in contact with the liquid.

[0024] In one embodiment, the auxiliary magnetic attraction assembly includes a magnetic aggregation magnet and a magnetic aggregation magnet driving mechanism. The magnetic aggregation magnet driving mechanism drives the magnetic aggregation magnet to move along the outer wall of the chamber to aggregate the magnetic particles at the preset position of the chamber.

[0025] In one embodiment, the magnetic focusing magnet moves along the length direction of the outer wall of the bottom of the chamber.

[0026] In one embodiment, the magnetic focusing magnet driving mechanism includes a magnetic focusing magnet driving motor, a driving gear connected to the magnetic focusing magnet driving motor, and a driving rack engaged with the driving gear. A magnetic focusing magnet fixing seat is arranged on the driving rack, and the magnetic focusing magnet is fixed on the magnetic focusing magnet fixing seat. The magnetic focusing magnet driving motor drives the driving gear to drive the driving rack to move along the length direction of the outer wall of the bottom of the chamber, thereby driving the magnetic focusing magnet to move along the length direction of the outer wall of the bottom of the chamber to quickly gather magnetic particles at the bottom of the chamber.

[0027] In one embodiment, the magnetic particle transfer assembly includes a magnetic rod, a magnetic rod sleeve fixing member, a magnetic rod moving mechanism and a magnetic rod sleeve moving mechanism for respectively driving the magnetic rod and the magnetic rod sleeve to move. The magnetic rod sleeve fixing member is used for connecting with the magnetic rod sleeve, and the magnetic rod moving mechanism and the magnetic rod sleeve moving mechanism drive the magnetic rod and the magnetic rod sleeve to move respectively, so that the magnetic rod and the magnetic rod sleeve cooperate to transfer the magnetic particles between the plurality of chambers.

[0028] In one embodiment, the magnetic rod moving mechanism and the magnetic rod sleeve moving mechanism drive the magnetic rod and the magnetic rod sleeve to move in the vertical direction and the length direction of the chamber respectively.

[0029] In one embodiment, the nucleic acid extraction device further includes a heating assembly, and the heating mode of the heating assembly is metal bath heating.

[0030] The nucleic acid extraction device further includes a first driving device for driving the heating assembly to approach and move away from the lysis chamber, or for driving the biological sample processing device bearing assembly to approach and move away from the heating assembly.

[0031] In one embodiment, before performing metal bath heating on the lysis chamber, the controller controls the heating assembly to heat the temperature to a preset temperature, and then controls the first driving device to act so that the heating assembly approaches the lysis chamber.

[0032] In one embodiment, the preset temperature is higher than the target temperature required for liquid lysis in the lysis chamber.

[0033] In one embodiment, the metal bath heating is in a manner of covering the outer wall of the side surface of the lysis chamber.

[0034] In one embodiment, the heating assembly includes at least one heating cavity for fitting the outer wall of the side surface of the lysis chamber, and the top and bottom of the heating cavity are open.

[0035] In one embodiment, the heating component uses a ceramic heating sheet as a heat source.

[0036] In one embodiment, the pipetting component is used to transfer a biological sample and a part of a reagent into the lysis chamber;

[0037] In one embodiment, the pipetting component includes a second driving device and a pipettor. The second driving device drives the pipettor to pick up a pipetting tip from the tip head loading area and move in the X, Y, and Z directions, so as to add the biological sample and a part of the reagent required for extraction into the lysis chamber.

[0038] In one embodiment, the magnetic focusing magnet moves along the height direction of the outer wall of the wider side of the chamber.

[0039] In one embodiment, multiple magnetic focusing magnets are provided, and one magnetic focusing magnet is provided between the chambers of every two adjacent biological sample processing devices. The magnetic focusing magnets are respectively connected to the magnetic focusing magnet driving mechanism and move along the height direction of the outer wall of the wider side of the chamber under the drive of the magnetic focusing magnet driving mechanism.

[0040] In one embodiment, the auxiliary magnetic attraction component further includes a magnet mounting plate. The magnetic focusing magnets are evenly arranged on the magnet mounting plate. Magnet movement guide rails and magnet power transmission parts arranged in the vertical direction are respectively provided at both ends of the magnet mounting plate. The magnet power transmission parts are respectively connected to the magnet movement guide rails and the magnetic focusing magnet driving mechanism. Both ends of the magnet mounting plate are respectively fixed on the magnet power transmission parts, and the magnet power transmission parts are fixed on the magnet movement guide rails through sliders.

[0041] In one embodiment, the magnetic focusing magnet driving mechanism includes a magnetic focusing magnet driving motor, magnet driving couplings arranged at both ends of the magnetic focusing magnet driving motor, and a conveyor belt transmission component. The conveyor belt transmission component moves in the vertical direction. One end of the magnet driving coupling is connected to the magnetic focusing magnet driving motor, and the other end is connected to the pulley of the conveyor belt transmission component. The magnet power transmission part is fixedly connected to the conveyor belt of the conveyor belt transmission component.

[0042] In one embodiment, the nucleic acid extraction device further includes a heating component. The heating component includes at least one heating cavity for attaching to the outer wall of the lysis chamber to heat the lysis chamber. Wherein, the top of the heating cavity and the side surface close to the magnetic focusing magnet are open.

[0043] In one embodiment, the heating method of the heating component is metal bath heating, and the heating component uses a ceramic heating sheet as a heat source.

[0044] The second aspect of the present invention provides a nucleic acid extraction method, which uses the nucleic acid extraction device described in any one or more of the above, and includes the following steps:

[0045] S1. Transfer the sample and part of the reagents required for lysis to the lysis chamber of the biological sample processing device;

[0046] S2. Use the magnetic rod and the magnetic rod sleeve to transfer the magnetic microparticles required for lysis to the lysis chamber, and at the same time perform metal bath heating on the lysis chamber to promote lysis;

[0047] S3. After lysis is completed, use the auxiliary magnetic attraction component to move along the outer wall of the lysis chamber to gather the magnetic microparticles in the lysis chamber at a preset position of the lysis chamber, and transfer the magnetic microparticles at the preset position to the cleaning chamber through the cooperation of the magnetic rod and the magnetic rod sleeve for cleaning;

[0048] S4. After cleaning is completed, transfer the magnetic microparticles in the cleaning chamber to the elution chamber through the cooperation of the magnetic rod and the magnetic rod sleeve, and at the same time perform metal bath heating on the elution chamber to complete elution.

[0049] In an optional embodiment, in step S2, using the magnetic rod and the magnetic rod sleeve to transfer the magnetic microparticles required for lysis includes:

[0050] S21. Place the magnetic rod sleeve into the magnetic microparticle storage chamber, and perform rapid up-and-down movement to mix the magnetic microparticles and their magnetic microparticle preservation solution;

[0051] S22. After mixing is completed, lower the magnetic rod into the magnetic rod sleeve, and slowly lower the magnetic rod and the magnetic rod sleeve from the liquid level of the magnetic microparticle storage chamber so that the magnetic microparticles gather at the bottom of the magnetic rod sleeve.

[0052] Compared with the prior art, the nucleic acid extraction device and extraction method of the present invention assist in gathering the magnetic microparticles in the chambers of the biological sample processing device through the auxiliary magnetic attraction component, so that the magnetic microparticles gather at a preset position of the chamber. Especially after lysis is completed, the magnetic microparticles in the lysis chamber are assisted in magnetic gathering, and after the magnetic microparticles at the preset position of the lysis chamber are gathered, the magnetic microparticles are transferred. This improves the transfer efficiency of magnetic microparticles from a large-volume lysis solution to an elution solution less than a hundred times its volume during large-volume nucleic acid extraction. At the same time, the biological sample processing device and the biological sample carrying device are small in volume and the magnetic loss rate is reduced.

[0053] The above technical features can be combined in various technically feasible ways to produce new embodiments as long as the object of the present invention can be achieved. BRIEF DESCRIPTION OF THE DRAWINGS

[0054] Hereinafter, the present invention will be described in more detail based on non-limiting examples only and with reference to the drawings. Among them:

[0055] Figure 1 Shows a schematic structural diagram of the nucleic acid extraction device according to the present invention;

[0056] Figure 2 Shows Figure 1 a schematic structural diagram of the auxiliary magnetic attraction component of the nucleic acid extraction device in

[0057] Figure 3 Shows Figure 1 a top view structural diagram of the biological sample processing device of the nucleic acid extraction device in

[0058] Figures 4 - 5 Shows Figure 1 a schematic structural distribution diagram of the sample loading area in

[0059] Figures 6 - 7 Shows Figure 1 a schematic structural diagram of the magnetic particle transfer component of the nucleic acid extraction device in

[0060] Figure 8 Shows Figure 1 a schematic structural diagram of the automatic sleeve-taking structure of the nucleic acid extraction device in

[0061] Figure 9 Shows a sectional view of the automatic sleeve-taking structure;

[0062] Figure 10 Shows Figure 8 an enlarged view of part A in

[0063] Figures 11 - 12 Shows Figure 1 a schematic structural diagram of the pipetting component in the nucleic acid extraction device in

[0064] Figure 13 Shows Figure 12 a schematic structural diagram of the pitch cam in

[0065] Figures 14 - 17 Shows Figure 1 a schematic structural diagram of the heating component in the nucleic acid extraction device in

[0066] Figure 18 Shows a schematic diagram of the temperature curve of the heating component;

[0067] Figure 19 Shows a schematic diagram of the process of auxiliary magnetic aggregation and magnetic transfer during the nucleic acid extraction of the present invention;

[0068] Figure 20 Shows a schematic structural diagram of a traditional die-repairing deep well plate;

[0069] Figure 21 Shows a schematic structural diagram of the die-repairing deep well plate of the present invention;

[0070] Figure 22 shows a sectional view of the deep well plate heating assembly structure;

[0071] Figure 23 shows a schematic structural diagram of another embodiment of the nucleic acid extraction device of the present invention;

[0072] Figures 24 - 26 shows a schematic structural diagram of another embodiment of the auxiliary magnetic attraction assembly of the nucleic acid extraction device of the present invention;

[0073] Figure 27 shows Figures 24 - 26 a schematic diagram of the process of the auxiliary magnetic attraction assembly assisting in magnetic aggregation and magnetic transfer;

[0074] Figure 28 shows a schematic structural diagram of another embodiment of the magnetic particle transfer assembly of the nucleic acid extraction device of the present invention;

[0075] Figures 29 - 31 shows a schematic structural diagram of another embodiment of the heating assembly of the nucleic acid extraction device of the present invention.

[0076] In the figure, the same components are labeled with the same reference numerals. The drawings are not drawn to actual scale.

[0077] Among them, the reference numerals are:

[0078] 1. Pipetting component; 2. Carrier component for biological sample processing device; 21. Biological sample processing device; 211. Lysis chamber; 212. First storage chamber for magnetic rod sleeve; 213. Magnetic particle storage chamber; 214. First cleaning chamber; 215. Second cleaning chamber; 216. Third cleaning chamber; 217. Second storage chamber for magnetic rod sleeve; 218. Elution chamber; 22. Placement area for biological sample processing device; 3, 3'. Magnetic particle transfer component; 31. X-axis movement mechanism; 32. Magnetic rod sleeve movement mechanism; 321, 321'. Magnetic rod sleeve drive motor; 322. Magnetic rod sleeve drive synchronous belt; 323, 323'. Magnetic rod sleeve movement lead screw; 324, 324'. First magnetic rod sleeve fixing plate; 325. First magnetic rod sleeve fixing piece; 326, 326'. First magnetic rod sleeve; 33. Magnetic rod movement mechanism; 331, 331'. Magnetic rod drive motor; 332. Magnetic rod drive synchronous belt; 333, 333'. Magnetic rod movement lead screw; 334, 334'. First magnetic rod fixing plate; 335, 335'. First magnetic rod; 34. Magnetic rod switching mechanism; 341. Magnetic rod switching synchronous belt fixing plate; 342. Magnetic rod switching synchronous belt; 343. Second magnetic rod; 344. Second magnetic rod fixing plate; 345. Second magnetic rod sleeve; 346. Second magnetic rod sleeve fixing plate; 35. First automatic magnetic rod sleeve picking mechanism; 351. First magnetic rod sleeve fixing piece; 352. Pressure spring; 353. Second magnetic rod sleeve fixing piece; 354. Pressure spring pressure plate; 355. First magnetic rod sleeve locking piece; 356. First magnetic rod sleeve locking drive piece; 357. Eccentric wheel; 36'. Y-axis movement mechanism; 361'. Y-axis movement drive motor; 362'. Y-axis movement belt assembly; 363'. Y-axis movement slide rail; 364'. Y-axis movement transmission seat; 365'. Y-axis slider; 4, 4'. Auxiliary magnetic attraction component; 41, 41'. Magnetic concentrating magnet; 42, 42'. Magnetic concentrating magnet fixing seat; 43, 43'. Magnetic concentrating magnet drive motor; 44. Driving gear; 44'. Magnet drive coupling; 45. Driving rack; 45'. Belt transmission assembly; 451' Transmission idler wheel; 452' Belt pulley; 453' Belt; 46' Magnet mounting plate, 47' Magnet power transmission part; 471' Slide block; 48' Magnet movement guide rail; 5. First driving device; 6. Deep well plate carrier component; 61. Modified deep well plate; 611. Lysis bin; 612. Magnetic particle storage bin; 613. First cleaning bin; 614. Second cleaning bin; 615. Third cleaning bin; 616. Elution bin; 617. Cavity; 62. Deep well plate placement area; 7. Octuplet tube loading area; 8. Partial reagent loading area; 9. Tip head loading area; 10. Sample area; 11. Three-axis X-axis drive component; 111. Three-axis X-axis drive motor; 112. Three-axis X-axis synchronous belt; 12. Three-axis Y-axis drive component; 121. Three-axis Y-axis drive motor; 122. Three-axis Y-axis synchronous belt; 123. Three-axis Y-axis transmission shaft; 13. Pipetting module;131. Z-axis drive assembly; 132. Pipettor; 133. Pipette tip; 134. Mounting backplane; 135. Z-axis drive motor; 136. Drive lead screw; 137. Spacing cam; 138. Spacing motor; 139. Spacing groove; 14, 14'. Heating assembly; 141. Ceramic heating element; 142, 142'. Heating cavity; 143'. Gap; 15. Elution heating assembly; 151. Magnetic rod sleeve drying chamber; 152. Elution chamber heating chamber; 16. Deep well plate heating assembly; 161. Lysis chamber heating chamber; 162. Elution chamber heating chamber; 17. Tip waste area; 18'. Heat dissipation assembly; 181'. Heat dissipation fan; Detailed implementation manners

[0079] The present invention will be further described in detail below with reference to the accompanying drawings of the specification and specific embodiments. It should be noted that as long as there is no conflict, the various embodiments in the present invention and the various features in each embodiment can be combined with each other, and the formed technical solutions are all within the protection scope of the present invention.

[0080] The parts not described in the present invention can be implemented by adopting or referring to the existing technologies.

[0081] Noun definitions

[0082] Modified deep well plate: A deep well plate whose structure is modified directly on the basis of the existing 96-well deep well plate.

[0083] Reaction system: A mixed solution of a sample and a lysis reagent.

[0084] Large-volume sample: A sample with a volume greater than 1 ml.

[0085] Medium-volume sample: A sample with a volume equal to 1 ml.

[0086] Small-volume sample: A sample with a volume less than 1 ml.

[0087] In nucleic acid extraction, the volume ratio of the sample to the lysis solution is about 1:2, which means that a 3-ml sample requires 6 ml of lysis solution, and the combined reaction system is 9 ml.

[0088] In one scenario, when extracting a small-volume nucleic acid sample from a large-volume reaction system, for example, extracting a 60-μl small-volume nucleic acid sample from 9 ml of large-volume liquid, if the pipetting method is used, the magnetic particles will be adsorbed on the side wall and then the liquid will be sucked away. Depending on the volume of each pipetting, the pipetting method requires multiple operations and is very time-consuming; if the magnetic transfer method is used to transfer the magnetic particles with a magnetic rod, since the volume of the lysis cavity becomes larger, a too-large magnetic rod will increase the volume of the self-developed reaction carrier, and if the magnetic rod is too small, it is difficult to quickly and completely aggregate the magnetic particles in the large-volume reaction system.

[0089] To solve this problem, through a large number of tests and research, the present invention proposes a large-volume nucleic acid extraction device, which uses an auxiliary magnetic attraction component to first gather magnetic particles at a preset position in the chamber of the biological sample processing device, and then transfers the magnetic particles gathered at the preset position through the cooperation of a magnetic rod and a magnetic rod sleeve, thereby improving the transfer efficiency of magnetic particles during large-volume nucleic acid extraction.

[0090] In addition, the magnetic rod and the magnetic rod sleeve mentioned in the process of large-volume nucleic acid extraction below are described by the first magnetic rod 335 and the first magnetic rod sleeve 326, and the magnetic rod and the magnetic rod sleeve mentioned in the process of nucleic acid extraction using a 96-well deep plate or a modified deep plate are described by the second magnetic rod 343 and the second magnetic rod sleeve 345.

[0091] Reference Figures 1 - 4 , the nucleic acid extraction device of the present invention is used for nucleic acid extraction of a large-volume sample, and at least includes:

[0092] A biological sample processing device carrier assembly 2 for carrying a biological sample processing device 21, the biological sample processing device 21 is formed as a strip-shaped consumable cartridge, including a plurality of chambers, and at least includes a lysis chamber 211. Among them, the lysis chamber 211 is mainly used to store lysis reagents and provide a reaction site for the lysis of biological samples and the binding of nucleic acids and magnetic particles.

[0093] A magnetic particle transfer assembly 3 for driving the first magnetic rod 335 and the first magnetic rod sleeve 326 to move, so as to transfer magnetic particles between the plurality of chambers;

[0094] An auxiliary magnetic attraction assembly 4 for driving the magnetic aggregation magnet 41 to move, so as to gather magnetic particles at a preset position in at least one of the plurality of chambers;

[0095] A pipetting assembly 1 for transferring biological samples and some reagents into the lysis chamber 211 of the biological sample processing device;

[0096] A controller for controlling the magnetic rod and the magnetic rod sleeve to move to a preset position for magnetic particle transfer.

[0097] The nucleic acid extraction device of the present application is provided with an auxiliary magnetic attraction component, which can assist in aggregating magnetic particles in the chamber of the biological sample processing device 21, enabling the magnetic particles to aggregate at a preset position in the chamber, and improving the transfer efficiency of magnetic particles during large-volume nucleic acid extraction. Especially when assisting in magnetic aggregation of the magnetic particles in the lysis chamber after lysis is completed, allowing the magnetic particles to aggregate at the preset position in the lysis chamber before transferring the magnetic particles, it improves the transfer efficiency of magnetic particles from a relatively large volume of lysate to an eluent that is less than a hundred times its volume. In this way, it no longer solely relies on the cooperation of a magnetic rod and a magnetic rod sleeve to complete the aggregation of magnetic particles in the chamber. Under the condition of ensuring the transfer efficiency of magnetic particles, the present application can use a magnetic rod and a magnetic rod sleeve with a smaller diameter, thereby making the biological sample processing device and the nucleic acid extraction device smaller in size. Moreover, through auxiliary magnetic aggregation, the magnetic particles in the chamber aggregate more completely, thereby reducing the magnetic loss rate.

[0098] In some alternative embodiments, the preset position is at the bottom of the chamber. In some more specific embodiments, the preset position is at the bottom of the lysis chamber 211. As Figure 2 and Figure 3 shown, in this embodiment, the lysis chamber of the biological sample processing device is flat and has a relatively large capacity. If simply using a magnetic rod and a magnetic rod sleeve to transfer magnetic particles results in a low transfer efficiency of magnetic particles, or requires a magnetic rod and a magnetic rod sleeve with a larger diameter, increasing the volume of the biological sample processing device and the nucleic acid extraction device, by using the auxiliary magnetic attraction component 4 to aggregate the magnetic particles at the bottom of the lysis chamber 211, the aggregation rate and transfer efficiency of the magnetic particles in the lysis chamber can be greatly improved.

[0099] In some specific embodiments, the nucleic acid is cell-free nucleic acid.

[0100] Cell-Free Circulating DNA (cfDNA) refers to DNA fragments that are released from apoptotic or necrotic cells and are free in the extracellular space. It is widely present in human serum, plasma, cerebrospinal fluid, urine, or saliva, and its concentration changes with tissue damage, cancer, and inflammatory responses. Cell-free nucleic acid can be used as a biomarker for predicting disease risk. We can screen, diagnose prenatal conditions in pregnant women, and screen, treat, and monitor the prognosis of major diseases such as tumors by detecting the dynamic changes in the levels of cell-free nucleic acid in plasma / serum. For example, in the bodies of pregnant mothers and tumor patients, some nucleic acid fragments come from the fetus and tumor tissues. By detecting this part of the cell-free nucleic acid, we can understand the genetic traits of the fetus and the disease conditions of tumor patients, providing non-invasive diagnoses for related detections, such as some congenital genetic diseases of the fetus and gene mutations in tumor patients. In more than 90% of healthy people, the cfDNA content in each milliliter of plasma is approximately 10 - 30 ng.

[0101] Although the application scope of cell-free nucleic acids is wide, due to reasons such as their low content in blood and the complexity of biological samples, the extraction of cell-free nucleic acids is not easy. How to quickly and completely extract cell-free nucleic acids from a large-volume sample has become the problem we are studying. And the nucleic acid extraction device of this application helps to quickly and completely extract cell-free nucleic acids.

[0102] In some alternative embodiments, the first magnetic rod 335 is used to be inserted into the first magnetic rod sleeve 326 so that magnetic particles are adsorbed on the outer surface of the bottom of the first magnetic rod sleeve 326.

[0103] In some alternative embodiments, such as Figure 2 and Figure 3 As shown, on the biological sample processing device 21, there are at least provided a lysis chamber 211, a washing chamber, a magnetic rod sleeve storage chamber, a magnetic particle storage chamber 213, and an elution chamber 218. Among them, the magnetic rod sleeve storage chamber pre-stores the first magnetic rod sleeve 326. One first magnetic rod sleeve 326 can be stored in one magnetic rod sleeve storage chamber. The lysis chamber 211, the washing chamber, and the elution chamber 218 are respectively pre-sealed with a lysis solution, a washing solution, and an elution solution for nucleic acid extraction, and the magnetic particle storage chamber is sealed with magnetic particles and a magnetic particle preservation solution. Specifically, the number of the washing chamber and the magnetic rod sleeve storage chamber can be set according to actual needs.

[0104] Figure 2 and Figure 3 shows a specific embodiment of a biological sample processing device 21. In the biological sample processing device 21 in this embodiment, there is provided a lysis chamber 211, a first washing chamber 214, a second washing chamber 215, a third washing chamber 216, a magnetic particle storage chamber 213, a first magnetic rod sleeve storage chamber 212, a second magnetic rod sleeve storage chamber 217, and an elution chamber 218 along the first direction. The first magnetic rod sleeve 326 is pre-stored in both the first magnetic rod sleeve storage chamber 212 and the second magnetic rod sleeve storage chamber 217. In the following description, for convenience of description, the biological sample processing device with this structure is taken as a specific example.

[0105] Preferably, the biological sample processing device 21 is formed as a strip-shaped consumable cartridge. Its lysis chamber 211 is a flat chamber and extends along the length direction of the strip-shaped consumable cartridge, so that there is a space for the magnetic rod sleeve to move horizontally in the length direction of the lysis chamber. The cross-section of the orifice of the lysis chamber 211 is a waist-shaped or a rectangle with large R corners at the four corners. As Figure 5 shown, the length direction is the X-axis direction when the biological sample processing device 21 is placed in the biological sample processing device placement area 22.

[0106] The cracking cavity structure of the flat cavity is conducive to temperature rise during cracking heating, and the design of the cross-sectional shape of the cavity opening can improve the capillary phenomenon in the cracking cavity, while avoiding that the magnetic particles suspended at the corners of the cracking cavity cannot be completely adsorbed by the magnetic rod sleeve, which helps to improve the recovery rate of magnetic particles.

[0107] In some alternative embodiments, in order to use a magnetic rod sleeve with a smaller diameter while ensuring the mixing effect of the magnetic rod sleeve in the cracking cavity and the magnetic focusing effect at the bottom of the magnetic rod sleeve, the diameter of the part of the first magnetic rod sleeve 326 in contact with the liquid in each chamber is 5.5 mm - 6.5 mm.

[0108] In some alternative embodiments, the opening cross-section of the cracking cavity 211 is waist-shaped. The width of the cross-section of the cracking cavity 211 is 1 mm - 3 mm greater than the diameter of the part of the first magnetic rod sleeve 326 in contact with the liquid, which is conducive to facilitating the movement of the magnetic rod sleeve in the vertical direction and the length direction of the cracking cavity during cracking, so as to promote cracking and achieve a mixing effect.

[0109] In some alternative embodiments, the auxiliary magnetic attraction assembly 4 at least includes a magnetic focusing magnet 41 and a magnetic focusing magnet driving mechanism. The magnetic focusing magnet driving mechanism drives the magnetic focusing magnet 41 to move along the outer wall of the corresponding chamber to quickly gather the magnetic particles at the bottom of the corresponding chamber, facilitating the accurate and rapid positioning of the magnetic rod sleeve and the magnetic rod to remove the magnetic particles.

[0110] In some preferred embodiments, the magnetic focusing magnet 41 moves along the length direction of the outer wall at the bottom of the corresponding chamber.

[0111] More specifically, as Figure 2 shown, the auxiliary magnetic attraction assembly 4 is arranged below the biological sample processing device 21. The magnetic focusing magnet driving mechanism includes a magnetic focusing magnet driving motor 43, a driving gear 44 connected to the magnetic focusing magnet driving motor 43, and a driving rack 45 engaged with the driving gear 44. A magnetic focusing magnet fixing seat 42 is arranged on the driving rack 45, and the magnetic focusing magnet 41 is fixed on the magnetic focusing magnet fixing seat 42. The magnetic focusing magnet driving motor 43 drives the driving gear 44 to drive the driving rack 45 to move along the length direction of the outer wall at the bottom of the chamber, especially the cracking cavity 211, so as to drive the magnetic focusing magnet 41 to move along the length direction of the outer wall at the bottom of the cracking cavity 211 to quickly gather the magnetic particles at a preset position at the bottom of the cracking cavity 211.

[0112] In some alternative embodiments, the magnetic focusing magnet 41 can move along the height direction of the side wall of the corresponding chamber. Specifically, the magnetic focusing magnet 41 can move along the height direction of the wider side wall of the cracking cavity 211 (such as the side of the cracking cavity shown in Figure 27 ).

[0113] Compared with the way of setting the magnetic concentrating magnet at the bottom, the way of setting the magnetic concentrating magnet on the side will make the magnetic concentrating speed faster and the magnetic concentrating effect better. Because at the same horizontal level (especially for the magnetic particles closer to the liquid surface), compared with the magnetic concentration at the bottom, the magnetic field is closer to the magnetic particles on the side, and the magnetic force received by the magnetic particles will be greater, so the magnetic concentration speed is faster and the magnetic concentration effect is better.

[0114] As Figures 23 - 26 shown, a replaceable auxiliary magnetic attraction assembly 4' is provided. In this embodiment, the auxiliary magnetic attraction assembly 4' is provided with a plurality of magnetic concentrating magnets 41'. And a magnetic concentrating magnet 41' is arranged between every two adjacent lysis chambers 211 of the biological sample processing device 21. The magnetic concentrating magnets 41' are respectively connected to the magnetic concentrating magnet driving mechanism and move along the height direction of the outer wall of the wider chamber under the drive of the magnetic concentrating magnet driving mechanism.

[0115] By using a single magnetic concentrating magnet to simultaneously perform magnetic attraction on the side walls of the chambers (especially the lysis chambers) of two biological sample processing devices, excellent magnetic attraction performance can be maintained while reducing the number of magnets and costs.

[0116] Specifically, as Figure 25 and Figure 26 shown, the auxiliary magnetic attraction assembly 4' further includes a magnet mounting plate 46'. The magnet mounting plate 46' extends along the X-axis direction (the arrangement direction of multiple biological sample processing devices 21). The magnetic concentrating magnets 41' can be uniformly arranged on the magnet mounting plate 46' through the magnetic concentrating magnet fixing seats 42'. The magnetic concentrating magnets 41' and the magnetic concentrating magnet fixing seats 12' extend into the space between adjacent biological sample processing devices 21. At both ends of the magnet mounting plate 46', there are respectively provided a magnet movement guide rail 48' and a magnet power transmission member 47' arranged in the vertical direction. The magnet power transmission member 47' is respectively connected to the magnet movement guide rail 48' and the magnetic concentrating magnet driving mechanism. Both ends of the magnet mounting plate 46' are respectively fixed on the magnet power transmission member 47'. The magnet power transmission member 47' is fixed on the magnet movement guide rail 48' through the slider 471'.

[0117] When the magnetic concentrating magnet driving mechanism acts, it drives the magnet power transmission member 47' to move in the vertical direction along the magnet movement guide rail 48', thereby driving the magnetic concentrating magnets 41' on the magnet mounting plate 46' to move along the height direction of the outer wall of the chamber of the biological sample processing device.

[0118] In some alternative embodiments, two magnet movement guide rails 48' can also be selected to be arranged on each side. The magnet power transmission member 47' is perpendicular to the magnet movement guide rail 48'. Both ends of the magnet power transmission member 47' are respectively fixed on the magnet movement guide rail 48' through the slider 471'.

[0119] Continue to refer to Figure 25 andFigure 26 In this embodiment, the magnetic flux concentrating magnet driving mechanism may include a magnetic flux concentrating magnet driving motor 43', a magnet driving coupling 44' disposed at both ends of the magnetic flux concentrating magnet driving motor 43', and a conveyor belt transmission assembly. The conveyor belt transmission assembly 45' moves in the vertical direction (i.e., the height direction of the chamber). The conveyor belt transmission assembly 45' includes a driving idler pulley 451', a conveyor belt driving pulley 452', and a conveyor belt 453'. One end of the magnet driving coupling 44' is connected to the magnetic flux concentrating magnet driving motor 43', and the other end is connected to the driving pulley 452' of the conveyor belt transmission assembly 45'. The magnet power transmission member 47' is fixedly connected to the conveyor belt 45'. The torque of the magnetic flux concentrating magnet driving motor 43' is transmitted to the driving pulley 452' through the magnet driving coupling 44'. The driving pulley 452' cooperates with the driving idler pulley 451' to drive the conveyor belt 453' to move in the vertical direction, thereby driving the magnet power transmission member 47' to move along the magnet movement guide 48'.

[0120] In some alternative embodiments, referring to Figure 6 and Figure 7 , the magnetic particle transfer assembly 3 includes a first magnetic rod 335, a first magnetic rod sleeve fixing member 325, a magnetic rod movement mechanism 33 and a magnetic rod sleeve movement mechanism 32 for respectively driving the first magnetic rod 335 and the first magnetic rod sleeve 326 to move. The first magnetic rod sleeve fixing member 325 is used to connect to the first magnetic rod sleeve 326. The magnetic rod movement mechanism 33 and the magnetic rod sleeve movement mechanism 32 respectively drive the first magnetic rod 335 and the first magnetic rod sleeve 326 to move, so that the first magnetic rod 335 and the first magnetic rod sleeve 326 cooperate to transfer magnetic particles between multiple chambers.

[0121] To avoid the electromagnet increasing the power of the instrument and the influence of the electromagnet heating on cleaning, the magnetic rod in this application is preferably made of a permanent magnet material.

[0122] Preferably, the magnetic rod movement mechanism 33 and the magnetic rod sleeve movement mechanism 32 respectively drive the first magnetic rod 335 and the first magnetic rod sleeve 326 to move in the vertical direction and the length direction of the chamber.

[0123] Optionally, referring to Figure 6 and Figure 7 , the magnetic particle transfer assembly 3 further includes an X-axis movement mechanism 31. The X-axis movement mechanism drives the magnetic rod sleeve movement mechanism 32 and the magnetic rod movement mechanism 33 to move in the X-axis direction. The magnetic rod movement mechanism 33 and the magnetic rod sleeve movement mechanism 32 respectively drive the first magnetic rod 335 and the first magnetic rod sleeve 326 to move in the Z-axis direction, so as to realize the movement cooperation of the first magnetic rod 335 and the first magnetic rod sleeve 326 in the X-axis and Z-axis directions, so as to drive the first magnetic rod 335 and the first magnetic rod sleeve 326 to move in the vertical direction and the length direction of the chamber.

[0124] Optionally, the magnetic rod sleeve movement mechanism 32 is connected to the first magnetic rod sleeve fixing plate 324. A first magnetic rod sleeve fixing member 325 is provided below the first magnetic rod sleeve fixing plate 324. The magnetic rod movement mechanism 33 is connected to the first magnetic rod fixing plate 334. A first magnetic rod 335 is provided below the first magnetic rod fixing plate 334. The first magnetic rod fixing plate 334 is arranged parallel to the upper side of the first magnetic rod sleeve fixing plate 324, and the first magnetic rod 335 corresponds to the first magnetic rod sleeve fixing member 325 and passes through the first magnetic rod sleeve fixing member 325.

[0125] In some specific embodiments, the magnetic rod sleeve movement mechanism 32 and the magnetic rod movement mechanism 33 are respectively fixed on the X-axis movement mechanism. The magnetic rod sleeve movement mechanism 32 further includes a magnetic rod sleeve driving motor 321 and a magnetic rod sleeve movement lead screw 323. The magnetic rod sleeve driving motor 321 is connected to the magnetic rod sleeve movement lead screw 323 through a magnetic rod sleeve driving synchronous belt 322. One end of the magnetic rod sleeve movement lead screw 323 is connected to the magnetic rod sleeve driving synchronous belt 322, and the other end is fixed on the X-axis movement mechanism 31. Similarly, the magnetic rod movement mechanism 33 further includes a magnetic rod driving motor 331 and a magnetic rod movement lead screw 333. The magnetic rod driving motor 331 is connected to the magnetic rod movement lead screw 333 through a magnetic rod driving synchronous belt 332. One end of the magnetic rod movement lead screw 333 is connected to the magnetic rod driving synchronous belt 332, and the other end is fixed on the X-axis movement mechanism 31.

[0126] A first magnetic rod sleeve fixing plate 324 is fixed on the magnetic rod sleeve movement lead screw 323. First magnetic rod sleeve fixing members 325 are respectively fixed below the first magnetic rod sleeve fixing plate 324. The first magnetic rod sleeve fixing members 325 are used to pick up the first magnetic rod sleeve 326. The first magnetic rod sleeve fixing plate 324 moves in the Z-axis direction along with the magnetic rod sleeve movement lead screw 323 driven by the magnetic rod sleeve driving motor 321, thereby driving the first magnetic rod sleeve 326 to move up and down in the Z-axis direction.

[0127] A first magnetic rod fixing plate 334 is fixed on the magnetic rod movement lead screw 333. The first magnetic rod fixing plate 334 is located above the first magnetic rod sleeve fixing plate 324 and corresponds to the first magnetic rod sleeve fixing member 325. A first magnetic rod 335 is provided below the first magnetic rod fixing plate 334. The first magnetic rod 335 passes through the first magnetic rod sleeve fixing member 325. The first magnetic rod fixing plate 334 can move in the Z-axis direction along with the magnetic rod movement lead screw 333 driven by the magnetic rod driving motor 331, thereby driving the first magnetic rod 335 to move up and down in the Z-axis direction, so that the first magnetic rod 335 extends into the first magnetic rod sleeve 326 or moves away from the first magnetic rod sleeve 326.

[0128] In some alternative embodiments, such as Figure 28As shown in the figure, this embodiment provides a replaceable magnetic particle transfer assembly 3'. The magnetic particle transfer assembly 3' in this embodiment is an improvement based on the above-mentioned magnetic particle transfer assembly 3. Different from the magnetic particle transfer assembly 3 in the above embodiment, the magnetic particle transfer assembly 3' in this embodiment is provided with a Y-axis movement mechanism 36' and a Z-axis movement mechanism. The magnetic rod sleeve movement mechanism 32 and the magnetic rod movement mechanism 33 in this embodiment drive the magnetic rod sleeve and the magnetic rod to move along the Z-axis direction ( Figure 1 the Z-axis direction in Figure 1 ), and the magnetic rod sleeve and the magnetic rod move along the Y-axis direction (

[0129] the Y-axis direction in

[0130] under the drive of the Y-axis movement mechanism. Figure 28 Specifically, referring to

[0131]

[0132]

[0133]

[0134] the magnetic rod sleeve movement mechanism 32 further includes a magnetic rod sleeve drive motor 321', a magnetic rod sleeve movement lead screw 323', and the magnetic rod sleeve drive motor 321' is connected to the magnetic rod sleeve movement lead screw 323' through a magnetic rod sleeve synchronous belt drive mechanism. A first magnetic rod sleeve fixing plate 324' is fixed on the magnetic rod sleeve movement lead screw 323'. Below the first magnetic rod sleeve fixing plate 324', first magnetic rod sleeve fixing members are respectively fixed. The first magnetic rod sleeve fixing members are used to pick up the first magnetic rod sleeve 326'. The first magnetic rod sleeve fixing plate 324' moves up and down in the Z-axis direction along with the magnetic rod sleeve movement lead screw 323' under the drive of the magnetic rod sleeve drive motor 321', thereby driving the first magnetic rod sleeve 326' to move up and down in the Z-axis direction. Similarly, the magnetic rod movement mechanism 33 further includes a magnetic rod drive motor 331', a magnetic rod movement lead screw 333', and the magnetic rod drive motor 331' is connected to the magnetic rod movement lead screw 333' through a magnetic rod synchronous belt drive mechanism. A first magnetic rod fixing plate 334' is fixed on the magnetic rod movement lead screw 333'. The first magnetic rod fixing plate 334' is located above the first magnetic rod sleeve fixing plate 324'. A first magnetic rod 335 is provided below the first magnetic rod fixing plate 334' corresponding to the first magnetic rod sleeve fixing member 325'. The first magnetic rod 335' passes through the first magnetic rod sleeve fixing member. The first magnetic rod fixing plate 334' is slidably connected to the Y-axis movement transmission seat 364' through a Y-axis slider 365'. The first magnetic rod fixing plate 334' can move up and down in the Z-axis direction along with the magnetic rod movement lead screw 333' under the drive of the magnetic rod drive motor 331', thereby driving the first magnetic rod 335' to move up and down in the Z-axis direction.

[0134] Further, the Y-axis movement mechanism 36' includes a Y-axis movement driving motor 361', a Y-axis movement belt assembly 362', a Y-axis movement slide rail 363' and a Y-axis movement transmission seat 364'. Among them, the Y-axis movement transmission seat 364' is respectively connected to the Y-axis movement belt assembly 362' and the Y-axis movement slide rail 363'. Specifically, the Y-axis movement transmission seat 364' is slidably arranged on the Y-axis movement slide rail 363' and is fixedly connected to the Y-axis movement belt assembly 362' through a connecting block (not shown in the figure). In this way, when the Y-axis movement driving motor 361' operates, it drives the Y-axis movement belt assembly 362' to drive the Y-axis movement transmission seat 364' to slide on the Y-axis movement slide rail 363'. The magnetic bar movement mechanism 33 and the magnetic bar sleeve movement mechanism are respectively fixedly connected to the Y-axis movement transmission seat 364', so as to move along the Y-axis direction with the Y-axis movement transmission seat 364'.

[0135] Compared with the prior art in which the user still needs to manually load the magnetic bar sleeve, the magnetic particle transfer assembly of the large-volume nucleic acid extraction device of the present invention further includes a first magnetic bar sleeve automatic sleeve-taking mechanism 35, as Figures 8 - 10 shown. The first magnetic bar sleeve automatic sleeve-taking mechanism includes a first magnetic bar sleeve fixing member 351 and a second magnetic bar sleeve fixing member 353. The first magnetic bar sleeve fixing member 351 is fixed on the first magnetic bar sleeve fixing plate 324 through an external thread. The second magnetic bar sleeve fixing member 353 is used to pick up the first magnetic bar sleeve 326. Among them, the second magnetic bar sleeve fixing member 353 is sleeved inside the first magnetic bar sleeve fixing member 351. A pressure spring 352 is arranged between the second magnetic bar sleeve fixing member 353 and the first magnetic bar sleeve fixing member 351, so that the second magnetic bar sleeve fixing member 353 can move inside the first magnetic bar sleeve fixing member 351 after being pressed. Further, the first magnetic bar sleeve 326 and the second magnetic bar sleeve fixing member 353 are in interference fit.

[0136] As Figures 8 - 10 shown, the pressure spring 352 extends upward to a pressure spring pressure plate 354 located on the upper surface of the first magnetic bar sleeve fixing plate 324. After the second magnetic bar sleeve fixing member 353 is pressed, it can move inside the first magnetic bar sleeve fixing member 351, so as to eliminate the influence of the height difference between individuals on the instability of picking up some of the first magnetic bar sleeves when picking up multiple first magnetic bar sleeves at the same time.

[0137] Meanwhile, to prevent the magnetic rod sleeve from falling off, the automatic magnetic rod sleeve picking mechanism 35 further includes a locking assembly, which includes a first magnetic rod sleeve locking drive 356, a first magnetic rod sleeve locking member 355, an eccentric wheel drive motor, and an eccentric wheel 357 disposed on the first magnetic rod sleeve fixing plate 324. After the first magnetic rod sleeve 326 is clamped on the second magnetic rod sleeve fixing member 353, the eccentric wheel drive motor drives the eccentric wheel 357 to drive the first magnetic rod sleeve locking drive 356 to the locking position to link the first magnetic rod sleeve locking member 355, and the first magnetic rod sleeve 326 is further locked by the first magnetic rod sleeve locking member 355.

[0138] As Figure 9 shown, the first magnetic rod sleeve locking member 355 is in a hook shape or an L shape, and the locking position of the first magnetic rod sleeve locking member 355 is below the pipe orifice of the first magnetic rod sleeve 326, and the magnetic rod sleeve is locked by abutting against the step at the pipe orifice of the first magnetic rod sleeve 326.

[0139] The specific process of picking up the sleeve and locking the magnetic rod sleeve is as follows: The drive motor of the X-axis movement mechanism drives the magnetic particle movement assembly to move above the magnetic rod sleeve storage cavity (such as the first magnetic rod sleeve storage cavity 212). The magnetic rod sleeve drive motor 321 drives the first magnetic rod sleeve fixing member 325 into the interior of the magnetic rod sleeve storage cavity, and continues to move downward. The first magnetic rod sleeve 326 is fixed on the first magnetic rod sleeve fixing member 325 by an interference tensioning method. Then, the magnetic rod sleeve drive motor 321 drives the magnetic rod sleeve movement mechanism 32 to move upward, and at the same time drives the first magnetic rod sleeve fixing member 325 to lift the first magnetic rod sleeve 326 upward. Then, the eccentric wheel motor drives the eccentric wheel 357 to drive the first magnetic rod sleeve locking drive 356 to the locking position to link the first magnetic rod sleeve locking member 355, so that the first magnetic rod sleeve locking member 355 is stuck at the step of the first magnetic rod sleeve 326, locking the connection between the first magnetic rod sleeve 326 and the first magnetic rod sleeve fixing member 325, preventing the risk of the first magnetic rod sleeve 326 falling off during the operation of the instrument, avoiding cross-contamination between samples, and ensuring the accuracy of the nucleic acid detection result after nucleic acid extraction.

[0140] As described above, the picking and locking of the first magnetic rod sleeve 326 are completed. Conversely, when the magnetic rod moves downward, the first magnetic rod sleeve is removed, which will not be elaborated here.

[0141] Preferably, the joint between the first magnetic rod sleeve and the second magnetic rod sleeve fixing member 353 can also be locked by interference with a hemispherical structure.

[0142] As Figure 4 and Figure 5As shown, the nucleic acid extraction device of the present invention further includes an eight-well tube loading area 7, a partial reagent loading area 8, a tip head loading area 9, a sample area 10, and a tip head waste area 17 in the sample bearing area. Among them, the partial reagent loading area 8 is used to load partial reagents, such as proteinase K, the eight-well tube loading area 7 is used to load eight-well tubes, the tip head loading area 9 is used to load disposable pipette tip heads 133 required for pipetting, the tip head waste area 17 is used to place discarded disposable tip heads, and the sample area 10 is used to load a sample rack that can hold multiple sample tubes.

[0143] In some alternative embodiments, such as Figure 14 and Figure 15 shown, the nucleic acid extraction device further includes a heating component 14, and the heating method of the heating component 14 is metal bath heating.

[0144] The nucleic acid extraction device further includes a first driving device 5, which is used to drive the heating component 14 to approach and move away from the lysis chamber 211, or to drive the biological sample processing device bearing component 2 to approach and move away from the heating component 14. The first driving device 5 can be a cam device or other liftable driving devices, such as synchronous belt lifting, rack and pinion lifting, crank slider lifting, link mechanism lifting, etc. Here, it is not limited thereto. Specifically, before performing metal bath heating on the lysis chamber 211, the controller controls the heating component 14 to heat the temperature to a preset temperature, which is higher than the target temperature required for lysis in the lysis chamber, and then controls the first driving device 5 to act so that the heating component 14 approaches the lysis chamber 211.

[0145] Since the liquid volume in the lysis chamber is much larger than the small volume of traditional microliters, the traditional solution of directly attaching the heating sheet and its metal bath to the heated body and then driving the heating sheet to heat is inefficient. The heating mode of using a metal bath reduces the cost of the heating sheet, and compared with the solution of directly attaching and then heating in the prior art, the heating rate is higher, and the heat source power used under the same heating rate is lower and the cost is also lower.

[0146] In other alternative embodiments, it is also possible to select a setting method in which the biological sample processing device 21 and the heating component 14 are relatively fixed. After the biological sample processing device 21 is loaded in place, it is directly located in the heating cavity 142 of the heating component 14.

[0147] Such as Figure 14 and 15 shown, the heating component 14 preferably includes at least one heating cavity 142 for attaching to the outer wall of the side of the lysis chamber 211, and preferably heats in a way that only covers the outer wall of the side of the lysis chamber 211.

[0148] Such as Figure 14 and 15As shown, the top and bottom of the heating cavity 142 are open. The top is open, which facilitates the entry of the cracking cavity 211 into the heating cavity 142 and its fitting with the heating cavity 142. The bottom is open, which facilitates the movement of the magnetic focusing magnet 41 along the length direction at the bottom of the cracking cavity 211 without interfering with the auxiliary magnetic focusing effect.

[0149] As Figure 16 and 17 shown, the heating assembly 14 preferably uses a ceramic heating sheet 141 as the heat source. The ceramic heating sheet 141 is arranged on the outer wall of the heating cavity 142, making the heat distribution more uniform, and there is no need for a heat dissipation device, which can further reduce the volume of the instrument.

[0150] In other alternative solutions, the heat source of the metal bath can also be a Peltier, a resistance heating rod, a resistance wire heating belt, etc.

[0151] More specifically, before starting the metal bath heating of the cracking cavity 211, that is, during the process of adding the sample and part of the reagent to the cracking cavity 211, the heating assembly 14 has already preheated the temperature to above the target temperature of the lysis solution. During lysis, through the first driving device 5, for example, it can be a lifting cam as in Figure 4 or Figure 5 to control the placement rack of the biological sample processing device to descend into the heating cavity 142 of the heating assembly 14 for heating, so that the temperature inside the lysis solution in the cracking cavity 211 starts to be heated directly without waiting for the metal bath to heat up, and the metal bath heating completely wraps the liquid below the liquid surface. In this way, even when the power of the heating sheet is not high, it can well meet the requirement of heating the large-volume liquid as a whole.

[0152] By restricting the heating cavity of the cracking cavity at a certain angle, it can be closely attached to the surface wall of the cracking cavity of the biological sample processing device, making the heat conversion efficiency higher. At the same time, a driving device is designed in this reaction area. By controlling the lifting of the placement rack of the biological sample processing device or the metal bath heating assembly, it is possible to heat the heating cavity to the target temperature, and at the same time, it will not affect the biological sample processing device during the heating stage. It can also control the self-developed consumables to be heated simultaneously in multiple channels, improving the uniformity of the reaction, and can avoid premature lysis of some samples, resulting in the degradation of nucleic acid molecules and affecting subsequent amplification detection.

[0153] The reason for improving the uniformity is that in the case of having multiple heating cavities, it is difficult to ensure that the heating rate of each heating cavity is the same. By using heating, multiple heating cavities can reach the same target temperature and then be attached to each cracking cavity, thus improving the uniformity of the reaction.

[0154] As Figure 18As shown in the figure, at time T0, the metal bath has been heated to the preheating temperature of the metal bath by the built-in heat source (ceramic heating sheet). At this time, the placement rack of the biological sample processing device descends to the heating position to start heating the lysis solution. When heated to time T2, the metal bath starts to descend to the target temperature value inside the liquid. At the same time, since the temperature of the metal bath is still higher than the temperature inside the liquid at this time, the temperature inside the liquid will still gradually increase, and the temperature of the metal bath will gradually decrease until it finally reaches the equilibrium temperature, which is also the target temperature inside the liquid.

[0155] Compared with the temperature curve of heating the metal bath and the liquid simultaneously, it can be seen that by heating the metal bath first and then heating the liquid, it is relatively simple to avoid temperature overshoot, reduce the impact of too high temperature on the extract, and the time for the metal bath to rise from room temperature to the target temperature can also be subtracted. Moreover, the preheating time of the metal bath is sufficient, and it only needs to be ensured that it can be heated to the preheating temperature of the metal bath within the time period from the start of the operation of the nucleic acid extraction device to the transfer of the magnetic particles into the lysis chamber. Therefore, the power of the heat source used does not need to be too high, and it can also well meet the requirement of heating a large volume of liquid as a whole. Therefore, using this method can reduce the power of the heat source and cost, and at the same time improve the heating rate of the temperature inside the liquid.

[0156] As Figures 29 - 31 shown, an embodiment of a replaceable heating component 14' is also provided. The heating component 14' in this embodiment is an improvement based on the heating component 14 in the above embodiment. The heating component 14' in this embodiment is particularly applicable to Figures 23 - 26 the auxiliary magnetic attraction component 4' shown in the figure.

[0157] Referring to Figures 29 - 31 , different from the heating component 14 in the above embodiment, the heating component 14' in this embodiment includes at least one heating cavity 142' for fitting against the outer wall of the lysis chamber 211 to heat the lysis chamber 211. Among them, the top of the heating cavity 142' and the side surface close to the magnetic aggregation magnet 41' are open.

[0158] As Figure 29 shown, the heating cavity 14' includes a plurality of the above-mentioned heating cavities 142'. The plurality of heating cavities 142' are connected to each other as a whole. A gap 143' for the movement of the magnetic aggregation magnet 41' is provided between every two adjacent heating cavities 142'. More specifically, the gap 143' is adapted to the thickness of the magnetic aggregation magnet 41' and the magnetic aggregation magnet fixing seat 42', so as to facilitate the movement of the magnetic aggregation magnet 41' along the height direction of the outer wall of the wider side of the lysis chamber 211 without interfering with the magnetic aggregation effect of the auxiliary magnetic aggregation magnet 41'.

[0159] In some alternative embodiments, the heating component 14' may further include a heating sheet pressing plate (not shown in the figure) to apply pressure to the ceramic heating sheet 141' so that it further adheres to the heating metal bath, thereby improving the usage efficiency of the ceramic heating sheet 141'. Optionally, the heating sheet pressing plate and the ceramic heating sheet 141' may be selectively disposed on the side wall of the closed side of the heating cavity 142' and the bottom of the heating cavity 142'.

[0160] In some preferred embodiments, the pipetting assembly includes a second driving device and a pipettor 132. The second driving device drives the pipettor 132 to pick up the pipetting tip 133 and move in the X-axis, Y-axis, and Z-axis directions to add the required biological sample and part of the reagent to the lysis chamber 211.

[0161] In some specific embodiments, as Figures 11 - 13 shown, the pipetting assembly 1 includes a three-axis X-axis driving assembly 11, a three-axis Y-axis driving assembly 12, and a pipetting module 13. Among them, the three-axis X-axis driving assembly includes a three-axis X-axis driving motor 111 and a three-axis X-axis synchronous belt 112 moving along the X-axis. The three-axis Y-axis driving assembly 12 includes a three-axis Y-axis driving motor 121, a three-axis Y-axis synchronous belt 122, and a three-axis Y-axis transmission shaft 123. The three-axis Y-axis driving motor 121 drives the three-axis Y-axis synchronous belt 122 to move along the Y-axis direction through the three-axis Y-axis transmission shaft 123. The three-axis X-axis driving assembly 11 is fixedly connected to the three-axis Y-axis synchronous belt 122 and can move synchronously with the three-axis Y-axis synchronous belt 122. The pipetting module 13 is fixedly connected to the three-axis X-axis synchronous belt 112 and can move synchronously with the three-axis X-axis synchronous belt 112. Among them, the pipetting module 13 includes a Z-axis driving assembly 131, a pipettor 132, and a pipetting tip 133. The pipettor 132 moves up and down along the Z-axis direction under the drive of the Z-axis driving assembly 131.

[0162] More specifically, the pipetting module 13 includes a mounting back plate 134. The Z-axis driving assembly 131 is mounted on the mounting back plate 134. The Z-axis driving assembly 131 includes a Z-axis driving motor 135 and a driving lead screw 136. The pipettor 132 is fixedly connected to the driving lead screw 136.

[0163] In other alternative embodiments, other combinations may also be selected for the driving assembly, not limited to the combination of a driving motor, a driving lead screw, and a synchronous belt. Similarly, a driving method such as a rack and pinion or a cam can also be selected.

[0164] Further, as Figure 12 and Figure 13 shown, since the hole pitch between each consumable (including the biological sample processing device and the deep well plate) is different, the pipetting module 13 includes at least two pipettors 132, and the two pipettors 132 are controlled for pitch adjustment through a pitch adjustment cam 137 and a pitch adjustment motor 138.

[0165] Specifically, the spacing action of the spacing control is completed by the spacing motor 138, the spacing cam 137 and the spacing cam bearing together. As Figure 13 shown, an arc-shaped spacing groove 139 is provided in the spacing cam 137. The two arc-shaped spacing grooves 139 are arranged oppositely, and the two ends of the arc part are staggered radially.

[0166] The rotation of the spacing cam 137 is controlled by the spacing motor 138, and the two pipettes 132 are pushed to separate or close by the spacing groove 139, so as to complete the purpose of the spacing movement, and any spacing adjustment between 9 mm and 54 mm can be satisfied.

[0167] Through this structural design, the pipetting module 13 is compact and saves space, and can meet the corresponding hole spacing requirements. Thus, the pipette 132 can move in the X, Y, and Z axes in the nucleic acid extraction device to perform pipetting work.

[0168] As Figure 14 and Figure 15 shown, the nucleic acid extraction device of the present invention further includes an elution heating component 15. The elution heating component 15 includes a magnetic rod sleeve drying cavity 151 and an elution cavity heating cavity 152, which are respectively used to fit the outer walls of the magnetic rod sleeve storage cavity (the second magnetic rod sleeve storage cavity 217) and the elution cavity 218 for metal bath heating.

[0169] Preferably, the elution heating component 15 further includes at least one heating source, and the magnetic rod sleeve drying cavity 151 and the elution cavity heating cavity 152 share a heating source.

[0170] The magnetic rod sleeve storage cavity transfers heat to the first magnetic rod sleeve 326 by means of heat conduction.

[0171] In some specific embodiments, the top and bottom of the magnetic rod sleeve drying cavity 151 are provided with openings, and the cross-section of the opening of the magnetic rod sleeve drying cavity 151 is an incomplete circle. The purpose of this is to avoid the adjacent chambers of the magnetic rod sleeve storage cavity and improve the heating efficiency.

[0172] As Figure 14 and 15As shown, since the drying chamber 151 of the magnetic rod sleeve is relatively close to the chamber of the biological sample processing device on the other side. Specifically, the drying chamber 151 of the magnetic rod sleeve is close to the cleaning chamber of the biological sample processing device, and the distance between the drying chamber 151 of the magnetic rod sleeve and the cleaning chamber is about 2.97 mm. As a result, the heating metal chamber at the position of the drying chamber 151 of the magnetic rod sleeve can only be an incomplete circle, that is, the heating metal chamber can only be arranged on the side far from the cleaning chamber. If the bottom of the drying chamber is closed on the basis of the incomplete circle, it will cause an increase in the mass of the drying chamber 151 of the magnetic rod sleeve, and correspondingly, the heating rate will decrease, reducing the heating efficiency. Therefore, this problem is avoided by arranging an opening at the bottom of the drying chamber.

[0173] In some other specific embodiments, the elution chamber heating chamber 152 is attached to the bottom outer wall and the side outer wall of the elution chamber 218.

[0174] Preferably, the drying chamber 151 of the magnetic rod sleeve and the elution chamber heating chamber 152 are arranged adjacent to each other. More preferably, they are designed as an integral unit. The drying chamber 151 of the magnetic rod sleeve and the elution chamber heating chamber 152 share a heating source. Therefore, preferably, there is a height difference between the drying chamber 151 of the magnetic rod sleeve and the elution chamber heating chamber 152, so as to avoid the elution chamber heating chamber coming into contact with the elution chamber prematurely when drying the magnetic rod sleeve, resulting in excessive evaporation of the liquid in the elution chamber and affecting the elution effect. At the same time, it can make the drying chamber 151 of the magnetic rod sleeve cover a larger area of the magnetic rod sleeve storage chamber, and the drying efficiency is higher.

[0175] By drying the magnetic rod storage chamber and the magnetic rod sleeve in the chamber, the dried magnetic microparticles and magnetic rod sleeve are moved into the elution chamber, avoiding the contamination of the elution liquid by the cleaning liquid, improving the nucleic acid recovery rate, and enhancing the reliability and accuracy of the subsequent amplification detection results. At the same time, the drying of the magnetic rod sleeve borrows the original heat source of the elution, and no additional cost will be incurred. During the large-volume automated extraction process, even under the sharp change of the liquid volume, the efficiency of magnetic microparticle aggregation can still be maintained, ensuring the nucleic acid recovery rate and purification degree.

[0176] As Figure 16 shown, the ceramic heating sheet 141 of the elution heating assembly 15 is arranged on the side wall of the drying chamber 151 of the magnetic rod sleeve close to the elution chamber heating chamber, so as to ensure the heating effects of the two chambers.

[0177] More preferably, a plurality of counterbores for placing temperature sensors are opened in the elution chamber heating chamber 152 and the drying chamber 151 of the magnetic rod sleeve. Through the temperature sensors, the temperature of different positions of the heat-conducting metal groove can be monitored, so as to realize the precise temperature control of the entire heat-conducting metal groove.

[0178] In some alternative embodiments, the nucleic acid extraction device of the present invention may further include a heat dissipation assembly 18', which includes a heat dissipation fan 181', to dissipate heat from the heating assembly 14 (heating assembly 14') and the elution heating assembly 15 after heating ends.

[0179] The heat dissipation assembly 18' is optionally disposed at the bottom of the heating assembly 14 (heating assembly 14') and the elution heating assembly 15, so as to help reduce the floor area of the nucleic acid extraction device.

[0180] In some alternative embodiments, the nucleic acid extraction device of the present invention further includes a nucleic acid extraction reaction area for medium and small volume samples, which includes a deep well plate carrier assembly for carrying a 96-well deep well plate and / or a modified deep well plate. The biological sample processing device serves as the nucleic acid extraction reaction area for large volume samples, and the 96-well deep well plate and / or the modified deep well plate serve as the nucleic acid extraction reaction areas for medium and small volume samples. Among them, the modified deep well plate serves as the nucleic acid extraction reaction area for medium volume samples, and the 96-well deep well plate serves as the nucleic acid extraction reaction area for small volume samples. The deep well plate carrier assembly 6 and the biological sample processing device carrier assembly 2 are arranged side by side along the placement direction of the multiple cavities of the biological sample processing device 21. As Figure 5 shown, they are arranged side by side along the X direction.

[0181] The movement range of the X-axis movement mechanism covers the biological sample processing device carrier assembly 2 and the deep well plate carrier assembly 6.

[0182] As Figure 5 shown, at least one biological sample processing device placement area 22 and a deep well plate placement area 62 are arranged side by side in sequence in the X-axis direction. Among them, multiple biological sample processing devices 21 are arranged side by side along the Y-axis direction in the biological sample processing device placement area 22, and at least one modified deep well plate 61 or 96-well deep well plate is arranged side by side along the Y-axis direction in the deep well plate placement area 62. The short side of the modified deep well plate or the 96-well deep well plate is along the X-axis direction.

[0183] Such an arrangement makes the spatial layout of the biological sample processing device and the deep well plate more reasonable, makes the internal layout of the nucleic acid extraction device more compact, has a higher space utilization rate, and the magnetic particle transfer assemblies for large volume, medium volume or small volume samples can share a set of shaft systems to save costs.

[0184] In some alternative embodiments, the modified deep well plate 61 has multiple holes, and the multiple holes form multiple sets of a lysis chamber 611, at least one washing chamber, and an elution chamber 616 arranged in sequence. More preferably, the modified deep well plate includes multiple sets of a lysis chamber 611, a magnetic particle storage chamber 612, at least one washing chamber, and an elution chamber 616 arranged in sequence along the width direction of the modified deep well plate.

[0185] In a specific embodiment, a lysis chamber is formed by connecting three adjacent holes, and at least one washing chamber refers to three washing chambers.

[0186] As Figure 20 and Figure 21 shown, Figure 20 The usage mode of the traditional die repair deep well plate is that the lysis chamber 611, magnetic particle storage chamber 612, washing chambers (the first washing chamber 613, the second washing chamber 614, the third washing chamber 615), and elution chamber 616 are arranged along the length direction of the 96-well deep well plate. When multiple lysis chambers 611, washing chambers, and elution chambers 616 are arranged along the width direction of the 96-well deep well plate, a single deep well plate can only satisfy a maximum of 8 samples for simultaneous extraction. Moreover, there are empty cavities 617 in the last 4 rows in the 96-well deep well plate that cannot be used, resulting in waste of the biological sample processing device.

[0187] Figure 21 The die repair deep well plate 61 in the embodiment of the present application, when using the layout as Figure 21 shown, that is, the lysis chamber 611, magnetic particle storage chamber 612, washing chambers (the first washing chamber 613, the second washing chamber 614, the third washing chamber 615), and elution chamber 616 of the die repair deep well plate 61 are arranged along the width direction (X-axis direction) of the die repair deep well plate, and multiple lysis chambers, washing chambers, and elution chambers are arranged along the length direction (Y-axis direction) of the 96-well deep well plate or the die repair deep well plate (when used vertically), a single die repair deep well plate can satisfy a maximum of 12 samples for simultaneous extraction.

[0188] In this embodiment, the lysis chamber, washing chambers, and elution chamber of the die repair deep well plate are arranged along the width direction of the deep well plate, and multiple lysis chambers, washing chambers, and elution chambers are arranged along the length direction of the deep well plate. Compared with the traditional die repair deep well plate arranged or used horizontally, it can maximize the utilization of the empty spaces in the deep well plate, avoid waste of some holes, save resources, and at the same time, it can also match the layout of the biological sample processing device. In this way, only one set of shaft systems can be used to be compatible with two different volume biological sample processing devices, reducing the instrument cost.

[0189] As Figure 4 and Figure 5As shown, in the nucleic acid extraction device of the present invention, in order to combine the modified deep well plate 61 and the biological sample processing device 21, while also controlling costs, reducing the overall power and size of the instrument, etc. The present invention vertically places the modified deep well plate 61 inside the nucleic acid extraction device. Since the nucleic acid extraction process inside the biological sample processing device is to gradually move the magnetic particles from the lysis chamber to the elution chamber, therefore, the magnetic particle transfer assembly only needs to have the X and Z axis movement directions to meet the design requirements. Thus, in this application, the modified deep well plate is placed vertically (such that each lysis chamber 611, magnetic particle storage chamber 612, cleaning chamber, and elution chamber 616 of the modified deep well plate 61 are located on the X axis), so that the magnetic particle transfer assembly can simultaneously perform magnetic particle transfer actions on the modified deep well plate 61 in the X and Z axes, enabling the two to use only one set of axis systems, reducing the instrument cost.

[0190] Due to the different spacing of different reaction holes between the biological sample processing device and the 96 - deep well plate and / or the modified deep well plate, in order to be compatible and used between the biological sample processing device and the deep well plate, the nucleic acid extraction device of the present invention provides two sets of magnetic rods and corresponding magnetic rod sleeves, and uses the magnetic rod switching mechanism 34 to switch between the two sets of magnetic rods and magnetic rod sleeves for use, so as to be respectively applied between the biological sample processing device and the deep well plate.

[0191] As Figure 6 and Figure 7 As shown, the magnetic rod switching mechanism 34 includes a magnetic rod switching synchronous belt fixing plate 341, a second magnetic rod fixing plate 344, and a second magnetic rod sleeve fixing plate 346. The magnetic rod switching synchronous belt fixing plate 341 is fixedly connected to the first magnetic rod sleeve fixing plate 324. On the magnetic rod switching synchronous belt fixing plate 341, there is a magnetic rod switching synchronous belt 342 and a moving slide rail arranged along the vertical direction, that is, the Z - axis direction.

[0192] Among them, the first magnetic rod fixing plate 334 can be connected to one end of the magnetic rod switching synchronous belt 342 through sheet metal. The second magnetic rod sleeve fixing plate 346 is connected to the first magnetic rod sleeve fixing plate 324. The second magnetic rod sleeve fixing plate 346 is provided with a second magnetic rod sleeve loading position for fixing the multi - joint magnetic rod sleeve (i.e., the second magnetic rod sleeve 345). The second magnetic rod fixing plate 344 is arranged parallel to the second magnetic rod sleeve fixing plate 346 above and is connected to the other end of the magnetic rod switching synchronous belt 342 through sheet metal, and the second magnetic rod 343 is provided on the second magnetic rod fixing plate 344 corresponding to the multi - joint magnetic rod sleeve.

[0193] When performing nucleic acid extraction, first, the X-axis motion mechanism 31 drives the magnetic rod sleeve motion mechanism 32 and the magnetic rod motion mechanism 33 to move to a suitable working position, and the magnetic rod switching mechanism switches the corresponding magnetic rod to descend. The magnetic rod sleeve motion mechanism 32 and the magnetic rod motion mechanism 33 cooperate to perform magnetic particle aspiration, gathering the magnetic particles inside the biological sample processing device at the bottom of the magnetic rod sleeve. Then, the magnetic rod sleeve and the magnetic rod are lifted and moved to the next reaction chamber, thus completing the transfer action of the magnetic particles.

[0194] When the magnetic rod drive motor 331 operates, the magnetic rod sleeve drive motor 321 is locked. At this time, there is a relative displacement between the first magnetic rod fixing plate 334 and the first magnetic rod sleeve fixing plate 324. The first magnetic rod fixing plate 334 drives the magnetic rod switching synchronous belt 342 to move. Relatively, the second magnetic rod 343 will be driven by the magnetic rod switching synchronous belt 342 to move in the opposite direction of the movement direction of the first magnetic rod fixing plate 334, thereby realizing the switching between the first and second magnetic rods. Similarly, when the magnetic rod drive motor 331 is locked and the magnetic rod sleeve drive motor 321 operates, the switching between the first and second magnetic rods can also be realized, and the process is similar to the above and will not be elaborated here.

[0195] In other alternative embodiments, the magnetic rod switching mechanism can also be driven by means of a gear rack or a cam, etc. Here, no limitation is imposed on it.

[0196] As Figure 22 shown, the nucleic acid extraction device of the present invention further includes a deep well plate heating assembly 16 for a modified deep well plate or a 96-well deep well plate. The deep well plate heating assembly 16 is a metal bath heating method. The deep well plate heating assembly 16 includes a lysis chamber heating chamber 161 and an elution chamber heating chamber 162. Among them, the lysis chamber heating chamber 161 heats in a way that completely covers the bottom of the lysis chamber. More preferably, the lysis chamber heating chamber 161 heats in a way that completely covers each well of the lysis chamber.

[0197] When processing small-volume samples, the lysis chamber, magnetic particle storage chamber, washing chamber, and elution chamber of the 96-well deep well plate are respectively arranged in the length direction of the 96-well deep well plate. Only one of the first 3 well positions corresponding to the lysis chamber of the modified deep well plate 61 of the present application in the width direction is selected to place the lysis solution, and the remaining 2 are vacant. For the 3 well positions corresponding to the washing chamber of the modified deep well plate 61 of the present application, if the small-volume sample only needs to wash the magnetic particles 2 times, then 2 washing chamber well positions are filled with the washing solution and 1 well position is vacant. Such an arrangement can process 12 samples. Compared with the traditional use of a 96-well deep well plate that can process 16 samples, in this embodiment, in order to ensure the nucleic acid extraction of the instrument for various volume samples, the deep well plate is utilized as fully as possible to reduce waste.

[0198] The second aspect of the present invention proposes a method for large-volume nucleic acid extraction using the above nucleic acid extraction device, including the following steps:

[0199] S1. Transfer the sample and some reagents required for lysis to the lysis chamber of the biological sample processing device;

[0200] Specifically, after loading the biological sample processing device 21 onto the biological sample processing device carrier assembly 2, the pipetting assembly 1 drives the pipette 132 to pick up the pipetting tip 133 and transfer the sample and some reagents (such as proteinase K required to promote lysis) required for lysis into the lysis chamber 211.

[0201] During this process, the proportion of the lysis solution in the lysis chamber is about 80%. This proportion can ensure that when the biological sample processing device 21 is used in, for example, the maximum system - 9ML system (3ml sample + 6ml lysis solution), there is still 20% of the remaining space to accommodate the volume of the magnetic rod sleeve and ensure that the magnetic rod sleeve will not cause the liquid to splash out of the lysis chamber when performing the mixing action.

[0202] S2. Use the first magnetic rod 335 and the first magnetic rod sleeve 326 to transfer the magnetic microparticles required for lysis to the lysis chamber, and at the same time perform metal bath heating on the lysis chamber to promote lysis; preferably, before performing metal bath heating on the lysis chamber 211, first heat the lysis metal bath of the heating assembly 14 to a preset temperature and higher than the target temperature in the liquid in the lysis chamber 211 required for lysis.

[0203] Specifically, the magnetic rod sleeve movement mechanism 32 moves above the first magnetic rod sleeve storage chamber 212 in cooperation with the X - axis movement mechanism. The first magnetic rod sleeve automatic sleeve - taking mechanism 35 extracts the first magnetic rod sleeve 326 from the first magnetic rod sleeve storage chamber 212 and locks it. After extracting the magnetic rod sleeve, the X - axis movement mechanism 31 drives the magnetic rod sleeve movement mechanism 32 to move to the magnetic microparticle storage chamber 213, puts the first magnetic rod sleeve 326 into the magnetic microparticle storage chamber 213, and performs rapid up - and - down movement to mix the magnetic microparticles and their magnetic microparticle preservation solution; after mixing is completed, lower the first magnetic rod 335 into the first magnetic rod sleeve 326, and slowly lower the first magnetic rod 335 and the first magnetic rod sleeve 326 from the liquid surface in the magnetic microparticle storage chamber 213 so that the magnetic microparticles gather at the bottom of the first magnetic rod sleeve 326.

[0204] The reason for using the first magnetic rod sleeve 326 to mix the magnetic microparticles and their magnetic microparticle preservation solution is that nanoscale magnetic microparticles are prone to agglomeration at the bottom of the magnetic microparticle storage chamber 213. If the magnetic microparticles are directly sucked away by the first magnetic rod sleeve 326 and transferred to the lysis chamber 211 of the large - volume reaction system, it is very difficult to disperse the magnetic microparticles. However, by adopting the method of first mixing the magnetic microparticles in the small - volume magnetic microparticle storage chamber 213 and then adsorbing the magnetic microparticles, the way of magnetic microparticle aggregation at the bottom of the magnetic rod sleeve is different from the way of directly adsorbing the agglomerated magnetic microparticles. The method of first mixing the magnetic microparticles and then adsorbing the magnetic microparticles is easier to disperse the magnetic microparticles when the magnetic microparticles are transferred to the lysis chamber of the large - volume reaction system.

[0205] After the mixing is completed, the magnetic bar driving motor 331 drives the first magnetic bar 335 to descend to the inner bottom surface of the first magnetic bar sleeve 326 through the magnetic bar movement lead screw 333. Then, the magnetic bar sleeve driving motor 321 and the magnetic bar driving motor 331 move together to drive the first magnetic bar sleeve 326 and the first magnetic bar 335 to move downward uniformly together and enter the magnetic particle storage cavity 213. When the first magnetic bar sleeve 326 enters the magnetic particle storage cavity 213 and contacts the liquid surface, the first magnetic bar sleeve 326 and the first magnetic bar 335 are continuously moved downward slowly together to gather the magnetic particles in the magnetic particle storage cavity 213 on the lower surface of the first magnetic bar sleeve 326. Subsequently, the magnetic bar movement mechanism 33 and the magnetic bar sleeve movement mechanism 32 drive the first magnetic bar 335 and the first magnetic bar sleeve 326 to rise together and move to the inside of the lysis cavity 211 under the cooperation of the X-axis movement mechanism. When the first magnetic bar sleeve 326 extends into the lysis liquid surface in the lysis cavity 211, the first magnetic bar 335 starts to move upward, leaves the first magnetic bar sleeve 326, and returns to the reset point, where the reset point can be the maximum displacement position where the first magnetic bar 335 moves vertically upward. At this time, the first magnetic bar sleeve 326 performs vertical up-and-down movement in the lysis liquid to mix and disperse the magnetic particles on the first magnetic bar sleeve 326 in the lysis liquid.

[0206] Meanwhile, the heating assembly is used to perform metal bath heating on the lysis cavity 211. During the heating process, the magnetic bar sleeve movement mechanism 32 drives the first magnetic bar sleeve 326 to perform rapid up-and-down and left-and-right mixing actions in the lysis liquid to mix the liquid in the lysis liquid. During this process, the temperature in the liquid is kept at a stable temperature until the lysis is completed.

[0207] Specifically, during the process of adding the sample and part of the reagent to the lysis cavity 211, the temperature has been preheated to be higher than the target temperature of the lysis liquid. During lysis, through the first driving device 5, for example, it can be the lifting cam as in Figure 4 or Figure 5 to control the placement rack of the biological sample processing device to descend into the heating cavity 142 of the heating assembly 14 for heating, so that the metal bath completely wraps the liquid below the liquid surface to promote lysis.

[0208] S3. After the lysis is completed, the auxiliary magnetic attraction assembly 4 is used to move along the outer wall of the lysis cavity 211 to gather the magnetic particles in the lysis cavity 211 at a preset position inside the lysis cavity 211, and transfer the magnetic particles at the preset position to the cleaning cavity through the cooperation of the first magnetic bar 335 and the first magnetic bar sleeve 326 for cleaning; further, preheating can also be performed on the elution metal bath.

[0209] As in Figure 19As shown, a schematic process of the magnetic particle concentrating magnet driving motor 43 during magnetic particle concentration is schematically shown. The magnetic particles therein are only schematically shown, not specifically referring to only one magnetic particle, nor reflecting the comparison of the diameter of one magnetic particle with the magnetic rod sleeve. The magnetic particles are at the nanoscale.

[0210] After the lysis is completed, the magnetic rod moving mechanism 33 moves the first magnetic rod 335 to the reset point, and the magnetic rod sleeve moving mechanism 32 drives the first magnetic rod sleeve 326 to move above the lysis solution level. The auxiliary magnetic particle concentrating magnet driving motor 43 drives the magnetic particle concentrating magnet 41 to slowly move along the length direction of the bottom of the lysis chamber 211 in the lysis chamber 211 ( Figure 19 as shown in ① therein), so as to gather the magnetic particles at the inner bottom of the lysis chamber 211 through magnetic attraction, facilitating the subsequent transfer of the magnetic particles using the first magnetic rod 335 and the first magnetic rod sleeve 326.

[0211] After the concentration is completed, move the magnetic particle concentrating magnet 41 to the reset origin. It should be noted that the magnetic force at the reset point will not affect the lysis chamber 221. Use the first magnetic rod 335 and the first magnetic rod sleeve 326 to transfer the magnetic particles to the cleaning chamber. The transfer process is similar to the process of transferring the magnetic particles from the magnetic particle storage chamber 213 to the lysis chamber 211. The magnetic rod driving motor 331 drives the first magnetic rod 335 to descend to the inner bottom surface of the first magnetic rod sleeve 326 through the magnetic rod moving lead screw 333. Then, the magnetic rod sleeve driving motor 321 and the magnetic rod driving motor 331 move together to drive the first magnetic rod sleeve 326 and the first magnetic rod 335 to move downward uniformly together and enter the lysis chamber 211. When the first magnetic rod sleeve 326 enters the lysis chamber 213 and contacts the liquid surface, continue to slowly move the first magnetic rod sleeve 326 and the first magnetic rod 335 downward together to gather the magnetic particles in the lysis chamber 211 on the lower surface of the first magnetic rod sleeve 326 ( Figure 19 as shown in ② therein), and then the magnetic rod moving mechanism 33 and the magnetic rod sleeve moving mechanism 32 drive the first magnetic rod 335 and the first magnetic rod sleeve 326 to rise together ( Figure 19 as shown in ③ therein), and move to the cleaning chamber under the cooperation of the X-axis moving mechanism for 2 to 3 times of cleaning ( Figure 19 as shown in ④ therein).

[0212] In the implementation mode of this embodiment, after the concentration is completed, move the magnetic particle concentrating magnet 41 to the reset point so that the magnetic attraction of the magnetic particle concentrating magnet 41 no longer affects the magnetic particles in the lysis chamber 211. In other implementation modes, it is also possible to move the biological sample processing device 21, or use the first driving device to move the biological sample processing device bearing assembly 2 to make the magnetic particles away from the magnetic field range of the magnetic particle concentrating magnet 41. Or adopt a combination of both to shorten the lateral moving distance of the magnetic particle concentrating magnet 41 and save the space occupied by the auxiliary magnetic particle concentrating magnetic component.

[0213] After the cleaning is completed, the magnetic particles in the cleaning chamber are aggregated at the bottom of the first magnetic rod sleeve 326 through the cooperation of the first magnetic rod 335 and the first magnetic rod sleeve 326, and the magnetically aggregated magnetic particles are transferred to the elution chamber 218 through the cooperation of the first magnetic rod 335 and the first magnetic rod sleeve 326. At the same time, the elution chamber 218 is heated by a metal bath to complete the elution.

[0214] Preferably, after the cleaning is completed, the first magnetic rod sleeve 326 is replaced with a new first magnetic rod sleeve 326 extracted from the second storage chamber 217 of the magnetic rod sleeve. The magnetic particles in the third cleaning chamber 216 (or the cleaning chamber where the last cleaning is performed) are aggregated at the bottom of the first magnetic rod sleeve 326 through the cooperation of the first magnetic rod 335 and the replaced first magnetic rod sleeve 326, and the magnetically aggregated magnetic particles are transferred to the elution chamber 218 through the cooperation of the first magnetic rod 335 and the replaced first magnetic rod sleeve 326. The transfer process is similar to the process of transferring magnetic particles from the magnetic particle storage chamber 213 to the lysis chamber 211, which will not be elaborated here. At the same time, the placement rack of the biological sample processing device is controlled to descend, and the elution chamber 218 is lowered to the elution chamber heating chamber 152 for metal bath heating to complete the elution.

[0215] After the elution is completed, the separated magnetic particles are transferred to the second storage chamber 217 of the magnetic rod sleeve through the cooperation of the first magnetic rod 335 and the first magnetic rod sleeve 326. The pipette is controlled by the pipetting assembly 1 to pick up the pipette tip 133 to transfer the extract in the elution chamber 218 to the corresponding octagonal tube for subsequent detection or storage.

[0216] In an alternative embodiment, step S4 specifically further includes:

[0217] S41. After the magnetic particle cleaning is completed, a new first magnetic rod sleeve 326 is replaced. Through the cooperation of the replaced first magnetic rod sleeve 326 and the first magnetic rod 335, the magnetic particles in the cleaning chamber are aggregated at the bottom of the first magnetic rod sleeve 326 and transferred from the cleaning chamber to the magnetic rod sleeve storage chamber (the second storage chamber 217 of the magnetic rod sleeve), and the first magnetic rod sleeve 326 and the magnetic particles aggregated on the outer surface of its bottom are dried by an elution metal bath.

[0218] Specifically, after the last cleaning of the magnetic particles is completed, the first magnetic rod sleeve 326 is driven to move above the first storage chamber 212 of the magnetic rod sleeve. The first magnetic rod 335 is driven by the magnetic rod driving motor 331 to move downward, ejecting the first magnetic rod sleeve 326 from the first magnetic rod sleeve fixing member 325 and falling back into the first storage chamber 212 of the magnetic rod sleeve. Then, the first magnetic rod 335 is driven to move above the second storage chamber 217 of the magnetic rod sleeve, and a new first magnetic rod sleeve 326 is taken out from the second storage chamber 217 of the magnetic rod sleeve through the first magnetic rod sleeve automatic sleeve taking mechanism 35. It is moved above the third cleaning chamber and cooperates with the first magnetic rod 335 to transfer the magnetic particles from the cleaning chamber to the second storage chamber 217 of the magnetic rod sleeve.

[0219] The transfer process of the magnetic particles is similar to the above-mentioned transfer process and will not be elaborated here.

[0220] After the magnetic particles are transferred to the second storage cavity 217 of the magnetic rod sleeve, the placement rack of the biological sample processing device is lowered by the first driving device 5, so that the second storage cavity 217 of the magnetic rod sleeve enters the magnetic rod sleeve drying cavity 151 of the elution metal bath for heating. At this time, the elution cavity 218 is kept separated from the elution cavity heating cavity 152 of the elution metal bath. At this time, the first magnetic rod sleeve 326 is controlled to descend and extend into the heated section of the second storage cavity 217 of the magnetic rod sleeve to dry the cleaning liquid remaining on its surface, so that the magnetic particles and the magnetic rod sleeve transferred into the elution cavity 218 are dry.

[0221] S42. After the drying is completed, the first magnetic rod sleeve 326 after drying transfers the magnetic particles aggregated on the outer surface of its bottom to the elution cavity 218. At the same time, the placement rack of the biological sample processing device is lowered by the first driving device 5, so that the elution cavity 218 enters the elution cavity heating cavity 152 of the elution metal bath, and the elution metal bath continues to heat for elution to separate the nucleic acid from the magnetic particles.

[0222] Two first magnetic rod sleeves are provided in the magnetic rod storage cavity of the biological sample processing device. After cleaning, the magnetic rod sleeve is replaced and dried, which can avoid the contamination of the subsequent results caused by the lysate and cleaning liquid remaining on the first magnetic rod sleeve, thereby improving the reliability and accuracy of the detection results, improving the purity of the extract and the recovery rate of nucleic acid. At the same time, the drying of the magnetic rod sleeve borrows the original heat source of the elution metal bath and does not increase additional costs.

[0223] The third aspect of the present invention also provides a method for extracting large-volume nucleic acid by using the above nucleic acid extraction device, including the following steps:

[0224] S1. Transfer the sample and part of the reagents required for lysis to the lysis cavity 211 of the biological sample processing device 21;

[0225] S2. Transfer the magnetic particles required for lysis to the lysis cavity 211 by using the first magnetic rod 335' and the first magnetic rod sleeve 326', and at the same time heat the lysis cavity 211 by metal bath to promote lysis; preferably, before heating the lysis cavity 211 by metal bath, first heat the lysis metal bath of the heating component 14' to a preset temperature and higher than the target temperature in the liquid required for lysis in the lysis cavity 211.

[0226] S3. After the lysis is completed, the auxiliary magnetic attraction assembly 4' is used to move along the height direction of the outer wall of the wider side of the lysis chamber 211, so as to gather the magnetic particles in the lysis chamber 211 at a preset position inside the lysis chamber 211, and transfer the magnetic particles at the preset position to the cleaning chamber through the cooperation of the first magnetic rod 335' and the first magnetic rod sleeve 326' for cleaning; further, the elution metal bath can be preheated.

[0227] As Figure 27 shown, a schematic process of the magnetic aggregation magnet driving motor 43' during magnetic aggregation is schematically shown. The magnetic particles therein are only schematically shown, not specifically referring to only one magnetic particle, nor reflecting the comparison between the diameter of one magnetic particle and the magnetic rod sleeve. The magnetic particles are at the nanometer level.

[0228] After the lysis is completed, the heating function of the heating assembly 14' is turned off. The magnetic rod movement mechanism 33 moves the first magnetic rod 335' to the reset point, the magnetic rod sleeve movement mechanism 32 drives the first magnetic rod sleeve 326' to move above the lysis liquid level, and the auxiliary magnetic aggregation magnet driving motor 43' drives the magnetic aggregation magnet 41' to move upward from the bottom of the lysis chamber 211 along the height direction of the lysis chamber 211 to the lysis liquid level ( Figure 27 as shown by ① in the figure), and then slowly descends to the bottom of the lysis chamber 211 ( Figure 27 as shown by ② in the figure). During the slow descent, the magnetic particles are enriched on the inner wall surface of the lysis chamber 211. Through the movement of the magnetic aggregation magnet 41', the magnetic particles are driven to slowly move downward and gather at the inner bottom of the bottom edge of the lysis chamber 211. At the same time, the magnetic aggregation magnet 41' stays at this position. This is because after the magnetic aggregation magnet 41' completes magnetic aggregation, before the magnetic rod descends, it is necessary for the magnetic aggregation magnet 41' to temporarily adsorb the magnetic particles at the bottom of the lysis chamber 211 to prevent the disturbance of the liquid flow during the descent of the magnetic rod sleeve, which may cause the magnetic particles to be brought back into the liquid, thus affecting the magnetic aggregation efficiency.

[0229] After the aggregation is completed, the magnetic particles are transferred to the cleaning chamber by the first magnetic rod 335' and the first magnetic rod sleeve 326'. The magnetic rod driving motor 331' drives the first magnetic rod 335' to descend to the inner bottom surface of the first magnetic rod sleeve 326' through the magnetic rod movement lead screw 333'. Then, the magnetic rod sleeve driving motor 321' and the magnetic rod driving motor 331' move together to drive the first magnetic rod sleeve 326' and the first magnetic rod 335' to move downward uniformly to the bottom of the lysis chamber 211 ( Figure 27 as shown by ③ in the figure). At this time, the magnetic aggregation magnet 41' moves downward to the reset point, and the first magnetic rod sleeve 326' and the first magnetic rod 335' start to move slowly back and forth left and right to gather the magnetic particles in the lysis chamber 211 on the outer surface of the first magnetic rod sleeve 326 ( Figure 27 as shown by ④ in the figure), and then the first magnetic rod 335 and the first magnetic rod sleeve 326 cooperate to move the magnetic particles into the cleaning chamber for cleaning ( Figure 27as shown in ⑤-⑨ in the figure).

[0230] S4. After the cleaning is completed, the elution chamber 218 is heated by a metal bath, and the magnetic particles in the cleaning chamber are aggregated at the bottom of the first magnetic rod sleeve 326' through the cooperation of the first magnetic rod 335' and the first magnetic rod sleeve 326', and the magnetically aggregated magnetic particles are transferred to the elution chamber 218 through the cooperation of the first magnetic rod 335' and the first magnetic rod sleeve 326'. Preferably, after the cleaning is completed, the elution metal bath heating function is turned on to preheat the elution chamber 218, and at the same time, the first magnetic rod sleeve 326' is replaced with a new first magnetic rod sleeve 326' extracted from the second storage chamber 217 of the magnetic rod sleeve. The magnetic particles in the third cleaning chamber 216 (or the cleaning chamber where the last cleaning is performed) are aggregated at the bottom of the first magnetic rod sleeve 326' through the cooperation of the first magnetic rod 335 and the replaced first magnetic rod sleeve 326', and the magnetically aggregated magnetic particles are transferred to the elution chamber 218 through the cooperation of the first magnetic rod 335' and the replaced first magnetic rod sleeve 326'. The transfer process is similar to the process of transferring magnetic particles from the magnetic particle storage chamber 213 to the lysis chamber 211, and will not be described in detail here.

[0231] After the elution is completed, the separated magnetic particles are transferred to the second storage chamber 217' of the magnetic rod sleeve through the cooperation of the first magnetic rod 335' and the first magnetic rod sleeve 326', and the extract in the elution chamber 218 is extracted for subsequent detection or storage.

[0232] The remaining steps not described in detail are similar to the steps of the above method and will not be described in detail here.

[0233] Unless otherwise defined, the technical terms or scientific terms used in the present invention shall have the ordinary meanings understood by those of ordinary skill in the art to which the present invention pertains. The terms "first", "second" and similar words used in the present invention do not denote any order, quantity or importance, but are only used to distinguish different components. Words such as "comprising" or "including" mean that the elements or objects appearing before this word cover the elements or objects listed after this word and their equivalents, without excluding other elements or objects. Words such as "connected" or "coupled" are not limited to physical or mechanical connections, but may include electrical connections, whether direct or indirect. In the description of the present invention, the orientation or positional relationship indicated by terms such as "vertical", "X-axis", "Y-axis" and "Z-axis" is based on the orientation or positional relationship shown in the drawings, and is only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation. When the absolute position of the object being described changes, the relative position relationship may also change accordingly. Therefore, it should not be construed as a limitation to the present invention.

[0234] At this point, those skilled in the art should recognize that although the present invention has been described with reference to the preferred embodiments, various improvements can be made to it and components thereof can be replaced with equivalents without departing from the scope of the present invention. In particular, as long as there is no structural conflict, the technical features mentioned in each embodiment can be combined in any way. The present invention is not limited to the specific embodiments disclosed in the text, but includes all technical solutions falling within the scope of the claims.

Claims

1. A nucleic acid extraction device for extracting nucleic acid from a large volume sample, characterized in that: include: A biological sample processing device carrying assembly, used for carrying a biological sample processing device, wherein the biological sample processing device comprises a plurality of chambers and at least one lysis chamber; A magnetic particle transfer assembly, used for driving the magnetic rod and the magnetic rod sleeve to move so that the magnetic particles can be transferred between the multiple chambers; An auxiliary magnetic attraction component, used for driving the magnetic collecting magnet to move so as to gather the magnetic particles at a preset position of at least one chamber of the plurality of chambers; The controller is used to control the magnetic rod and the magnetic rod sleeve to move to the preset position to transfer the magnetic particles.

2. The nucleic acid extraction device according to claim 1, characterized in that: The lysis chamber is used to store lysis reagents and provide a reaction site for lysis of biological samples and combination of nucleic acids and magnetic particles.

3. The nucleic acid extraction device according to claim 2, characterized in that: The nucleic acid is free nucleic acid.

4. The nucleic acid extraction device according to claim 1, characterized in that: The preset position is located at the bottom of the chamber.

5. The nucleic acid extraction device according to claim 1, characterized in that: The preset position is located at the bottom of the lysis chamber.

6. The nucleic acid extraction device according to claim 1, characterized in that: The magnetic bar is used to be inserted into the magnetic bar sleeve so that the magnetic particles are adsorbed on the bottom outer surface of the magnetic bar sleeve.

7. The nucleic acid extraction device according to claim 6, characterized in that: The chamber of the biological sample processing device further comprises at least a cleaning chamber, a magnetic rod sleeve storage chamber, a magnetic particle storage chamber and an elution chamber, and the magnetic rod sleeve storage chamber stores the magnetic rod sleeve.

8. The nucleic acid extraction device according to claim 7, characterized in that: The diameter of the portion where the magnetic rod sleeve contacts the liquid in the chamber is 5.5 mm to 6.5 mm.

9. The nucleic acid extraction device according to claim 8, characterized in that: The opening cross section of the cracking chamber is waist-shaped.

10. The nucleic acid extraction device according to claim 9, characterized in that: The cross-sectional width of the lysis chamber is 1 mm to 3 mm greater than the diameter of the portion where the magnetic rod sleeve contacts the liquid.

11. The nucleic acid extraction device according to claim 1, characterized in that: The auxiliary magnetic attraction component includes a magnetic focusing magnet and a magnetic focusing magnet driving mechanism. The magnetic focusing magnet driving mechanism drives the magnetic focusing magnet to move along the outer wall of the chamber to gather the magnetic particles at a preset position of the chamber.

12. The nucleic acid extraction device according to claim 11, characterized in that: The magnetic focusing magnet moves along the length direction of the outer wall of the bottom of the chamber.

13. The nucleic acid extraction device according to claim 12, characterized in that: The magnetic magnet driving mechanism includes a magnetic magnet driving motor, a driving gear connected to the magnetic magnet driving motor, and a driving rack meshing with the driving gear. A magnetic magnet fixing seat is provided on the driving rack, and the magnetic magnet is fixed on the magnetic magnet fixing seat. The magnetic magnet driving motor drives the driving gear to drive the driving rack to move along the length direction of the bottom outer wall of the chamber, thereby driving the magnetic magnet to move along the length direction of the bottom outer wall of the chamber to quickly gather the magnetic particles at the bottom of the chamber.

14. The nucleic acid extraction device according to claim 6, characterized in that: The magnetic particle transfer assembly includes a magnetic rod, a magnetic rod sleeve fixing part, a magnetic rod movement mechanism and a magnetic rod sleeve movement mechanism for respectively driving the magnetic rod and the magnetic rod sleeve to move, the magnetic rod sleeve fixing part is used to be connected to the magnetic rod sleeve, and the magnetic rod movement mechanism and the magnetic rod sleeve movement mechanism respectively drive the magnetic rod and the magnetic rod sleeve to move, so that the magnetic rod and the magnetic rod sleeve cooperate to transfer the magnetic particles between the multiple chambers.

15. The nucleic acid extraction device according to claim 14, characterized in that: The magnetic bar movement mechanism and the magnetic bar sleeve movement mechanism respectively drive the magnetic bar and the magnetic bar sleeve to move in the vertical direction and the length direction of the chamber.

16. The nucleic acid extraction device according to claim 1, characterized in that: The nucleic acid extraction device further comprises a heating component, and the heating method of the heating component is metal bath heating; The nucleic acid extraction device further comprises a first driving device for driving the heating component to approach and move away from the lysis chamber, or for driving the biological sample processing device carrying component to approach and move away from the heating component.

17. The nucleic acid extraction device according to claim 16, characterized in that: Before the cracking chamber is heated by a metal bath, the controller controls the heating component to heat the temperature to a preset temperature, and then controls the first driving device to operate so that the heating component is close to the cracking chamber.

18. The nucleic acid extraction device according to claim 17, characterized in that: The preset temperature is higher than the target temperature required for liquid decomposition in the decomposition chamber.

19. The nucleic acid extraction device according to claim 16, characterized in that: The metal bath is heated in a manner that covers the outer wall of the side of the cracking chamber.

20. The nucleic acid extraction device according to claim 16, characterized in that: The heating assembly includes at least one heating cavity, and the heating cavity is used to fit the outer wall of the side of the cracking cavity, and the top and bottom of the heating cavity are opened.

21. The nucleic acid extraction device according to claim 16, characterized in that: The heating component uses a ceramic heating plate as a heat source.

22. The nucleic acid extraction device according to claim 1, characterized in that: The nucleic acid extraction device also includes a liquid transfer component for transferring biological samples and part of the reagents into the lysis chamber.

23. The nucleic acid extraction device according to claim 22, characterized in that: The pipetting assembly includes a second driving device and a pipette, and the second driving device drives the pipette to pick up the pipette tip and move it in the X, Y, and Z directions to add the biological sample and part of the reagent required for extraction into the lysis chamber.

24. The nucleic acid extraction device according to claim 11, characterized in that: The magnetic focusing magnet moves along the height direction of the outer wall of the wider side of the chamber.

25. The nucleic acid extraction device according to claim 24, characterized in that: There are multiple magnetic focusing magnets, and a magnetic focusing magnet is arranged between every two adjacent chambers of the biological sample processing device. The magnetic focusing magnets are respectively connected to the magnetic focusing magnet driving mechanism and move along the height direction of the outer wall of the wider side of the chamber under the drive of the magnetic focusing magnet driving mechanism.

26. The nucleic acid extraction device according to claim 25, characterized in that: The auxiliary magnetic attraction component also includes a magnet mounting plate, the magnetic focusing magnets are evenly arranged on the magnet mounting plate, and the two ends of the magnet mounting plate are respectively provided with a magnet movement guide rail and a magnet power transmission component arranged in a vertical direction, and the magnet power transmission component is respectively connected to the magnet movement guide rail and the magnetic focusing magnet driving mechanism, and the two ends of the magnet mounting plate are respectively fixed on the magnet power transmission component, and the magnet power transmission component is fixed on the magnet movement guide rail through a slider.

27. The nucleic acid extraction device according to claim 26, characterized in that: The magnetic magnet driving mechanism includes a magnetic magnet driving motor, a magnet driving coupling arranged at both ends of the magnetic magnet driving motor and a conveyor belt transmission assembly. The conveyor belt transmission assembly moves in a vertical direction. One end of the magnet driving coupling is connected to the magnetic magnet driving motor, and the other end is connected to the drive pulley of the conveyor belt transmission assembly. The magnet power transmission component is fixedly connected to the conveyor belt of the conveyor belt transmission assembly.

28. The nucleic acid extraction device according to any one of claims 24 to 27, characterized in that: The nucleic acid extraction device also includes a heating component, which includes at least one heating cavity for adhering to the outer wall of the lysis cavity to heat the lysis cavity, wherein the top of the heating cavity and the side close to the magnetic focusing magnet are opened.

29. The nucleic acid extraction device according to claim 28, characterized in that: The heating method of the heating component is metal bath heating, and the heating component uses a ceramic heating plate as a heat source.

30. A method for extracting nucleic acid, using the nucleic acid extraction device according to any one of claims 1 to 29, characterized in that: The following steps are involved: S1. Transferring the sample and some reagents required for lysis into the lysis chamber of the biological sample processing device; S2. Using a magnetic rod and a magnetic rod sleeve to transfer the magnetic particles required for lysis to a lysis chamber, while heating the lysis chamber with a metal bath to promote lysis; S3. After the lysis is completed, the auxiliary magnetic suction component is moved along the outer wall of the lysis chamber to gather the magnetic particles in the lysis chamber at a preset position in the lysis chamber, and the magnetic particles in the preset position are transferred to the cleaning chamber for cleaning through the cooperation of the magnetic rod and the magnetic rod sleeve; S4. After the cleaning is completed, the magnetic particles in the cleaning chamber are transferred to the elution chamber by the cooperation of the magnetic rod and the magnetic rod sleeve, and the elution chamber is heated by a metal bath to complete the elution.

31. The method for extracting nucleic acid according to claim 30, characterized in that: In step S2, the magnetic particles required for lysis are transferred to the lysis chamber using a magnetic rod and a magnetic rod cover, including: S21. Place the magnetic rod cover into the magnetic particle storage chamber and perform rapid up and down motion to mix the magnetic particles and the magnetic particle storage solution; S22. After the mixing is completed, the magnetic rod is lowered into the magnetic rod sleeve, so that the magnetic rod and the magnetic rod sleeve slowly descend from the liquid surface of the magnetic particle storage chamber, so that the magnetic particles gather at the bottom of the magnetic rod sleeve.

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