Sample processing system and biochemical reaction system

Abstract

A sample processing system and a biochemical reaction system. The sample processing system comprises a storage module, a transfer module, at least one incubation module and a control module; the storage module is configured to store a sample required for a biochemical reaction; the incubation module is configured to provide a preset temperature for the biochemical reaction; the transfer module is configured to transfer the sample; and the control module is configured to control the transfer module and the incubation module to work collaboratively. The sample processing system uses a modular design, can realize full-process automated sample processing, improves the efficiency and effect of sample processing, and is particularly suitable for automated preparation of single-molecule sequencing libraries.

Description

Sample processing system and biochemical reaction system Technical Field

[0001] The present application relates to the technical field of sample processing, and in particular to a sample processing system and a biochemical reaction system. Background Art

[0002] Before conducting biochemical reactions in fields such as biology, medicine, and chemistry, samples often require pretreatment. For example, before gene sequencing, biological samples must be processed to construct sequencing libraries. The ultimate goal of library construction is to construct target fragments of the desired length and structure compatible with the sequencing platform. Currently, the market is dominated by second-generation high-throughput sequencing technologies, with read lengths typically in the hundreds of base pairs. Adapter-based library construction is a widely used and well-established technology. The basic process for library construction using second-generation sequencing technology involves first fragmenting the extracted genomic DNA through physical or enzymatic shearing. The fragmented DNA ends undergo blunt-end repair and A addition, followed by ligation with DNA ligase, followed by ligation with adapters. Finally, PCR amplification is performed, interspersed with purification and sorting steps to complete the library construction.

[0003] With the rapid development of high-throughput sequencing technology, single-molecule sequencing has been developed to the third generation of sequencing, with sequencing read lengths ranging from tens of kb to even 100 kb. However, the library construction methods mentioned above for second-generation sequencing technology are not suitable for single-molecule sequencing library construction.

[0004] Summary of the Invention

[0005] In view of this, in order to solve at least one of the above technical problems, it is necessary to propose a sample processing system.

[0006] In addition, the present application also provides a biochemical reaction system using the aforementioned sample processing system.

[0007] In a first aspect, the present application provides a sample processing system, which includes: a storage module, a transfer module, at least one incubation module and a control module, wherein the storage module is configured to store samples required for biochemical reactions; the incubation module is configured to provide a preset temperature for the biochemical reaction; the transfer module is configured to transfer the samples; and the control module is configured to control the transfer module and the incubation module to operate collaboratively.

[0008] In a second aspect, embodiments of the present application provide another sample processing system, comprising: a storage module, a transfer module, at least one incubation module, a separation and purification module, a first mixing module, a second mixing module, a cover switch module, and a control module, wherein the storage module is configured to store samples required for biochemical reactions; the incubation module is configured to provide a preset temperature for the biochemical reactions; the transfer module comprises a pipetting device and a transfer device, the pipetting device being configured to aspirate and transfer the samples, and the transfer device being configured to transfer reaction containers loaded with the samples; and the control module being configured to control the transfer module, the incubation module, the separation and purification module, the first mixing module, the second mixing module, and the cover switch module to operate in coordination. The control module is further configured to allow an operator to select whether to execute a sample processing protocol that does not include the transfer device, the first mixing module, the second mixing module, and the cover switch module, or to execute a sample processing protocol that includes at least one of the transfer device, the first mixing module, the second mixing module, and the cover switch module.

[0009] In a third aspect, an embodiment of the present application provides a biochemical reaction system, which includes a biochemical reaction device and the sample processing system as described above.

[0010] The sample processing system provided in the embodiments of this application adopts a modular design, which can realize a fully automated sample processing process without manual intervention, thereby improving the efficiency and effectiveness of sample processing. This sample processing system can be used to realize the automated preparation of single-molecule sequencing libraries, which have the advantages of high concentration, long fragments, and large library quantities. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] FIG1 is a system framework diagram of a sample processing system provided in one embodiment of the present application.

[0012] FIG2 is a schematic structural diagram of a sample processing system provided in an embodiment of the present application with part of the outer shell removed.

[0013] FIG3 is a schematic structural diagram of the consumable carrier in FIG2 from one perspective.

[0014] FIG4 is a schematic diagram of the structure of the consumables loaded on the consumable carrier in FIG3 .

[0015] FIG5 is a schematic structural diagram of the consumable carrier in FIG3 from another perspective.

[0016] FIG6 is a cross-sectional view along line AA of FIG3 .

[0017] FIG7 is a cross-sectional view of a reaction container provided in one embodiment of the present application.

[0018] FIG8 is a schematic structural diagram of the reaction container supported on the incubation module in FIG2 .

[0019] FIG. 9 is an exploded view of the incubation device in FIG. 8 .

[0020] FIG10 is a partial cross-sectional view of a heating tank after a reaction container is placed in the heating tank in one embodiment of the present application.

[0021] FIG11 is a partial cross-sectional view along line BB in FIG8 .

[0022] FIG12 is a schematic structural diagram of the thermal insulation block in FIG9 .

[0023] FIG13 is a schematic diagram of a three-dimensional structure in which a reaction container is placed in the first mixing device in FIG2 and is in a blocking state.

[0024] FIG14 is a schematic diagram of a three-dimensional structure of the first mixing device shown in FIG2 in which a reaction container is placed and is in a non-blocking state.

[0025] FIG15 is a schematic diagram of the three-dimensional structure of the mixing device in FIG13 .

[0026] FIG16 is a partially cutaway schematic diagram of the three-dimensional structure of the mixing device in FIG15 .

[0027] FIG17 is a cross-sectional view taken along CC of FIG15 .

[0028] FIG18 is a cross-sectional view showing a reaction vessel placed in the mixing device shown in FIG17 .

[0029] FIG19 is a schematic structural diagram of the drive shaft in FIG18 .

[0030] FIG20 is a schematic diagram of the three-dimensional structure of the blocking device in FIG13.

[0031] FIG. 21 is an exploded view of the blocking device shown in FIG. 20 .

[0032] FIG22 is a cross-sectional view of a portion of the sample processing system shown in FIG2 .

[0033] FIG23 is an enlarged view of portion A in FIG22 .

[0034] FIG24 is a schematic structural diagram of the separation and purification module in FIG23 .

[0035] FIG25 is a system framework diagram of a sample processing system provided in another embodiment of the present application.

[0036] FIG26 is a system framework diagram of a sample processing system provided in yet another embodiment of the present application.

[0037] Figure 27 is a schematic structural diagram of an embodiment of the present application in which a reaction container is placed between two second adsorption devices.

[0038] FIG28 is a system framework diagram of a sample processing system provided in yet another embodiment of the present application.

[0039] FIG29 is a system framework diagram of a sample processing system provided in yet another embodiment of the present application.

[0040] FIG30 is a system framework diagram of a sample processing system provided in yet another embodiment of the present application.

[0041] FIG31 is a system framework diagram of a sample processing system provided in yet another embodiment of the present application.

[0042] FIG32 is a system block diagram of a biochemical reaction system provided in one embodiment of the present application.

[0043] The following specific implementation methods will further illustrate the present application in conjunction with the above-mentioned drawings. DETAILED DESCRIPTION

[0044] The following will clearly and completely describe the technical solutions in the embodiments of the present application in combination with the drawings in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all of the embodiments.

[0045] It should be noted that when a component is referred to as being "fixed to" or "mounted on" another component, it may be directly on the other component or there may be a central component. When a component is referred to as being "disposed on" another component, it may be directly on the other component or there may be a central component. As used herein, the term "and / or" includes all and any combinations of one or more of the relevant listed items.

[0046] It should be noted that although a logical order is shown in the flowchart, in some cases, the steps shown or described may be performed in an order different from that in the flowchart. The method disclosed in the embodiments of the present application includes one or more steps or actions for implementing the method. The method steps and / or actions can be interchangeable with each other without departing from the scope of the claims. Unless a specific order of steps or actions is specified, the order and / or use of specific steps and / or actions can be modified without departing from the scope of the claims.

[0047] Example 1

[0048] Referring to Figures 1 and 2, one embodiment of the present application provides a sample processing system 100, comprising: a storage module 1, a transfer module 2, at least one incubation module 3, and a control module 4. The storage module 1 is configured to store samples required for biochemical reactions; the incubation module 3 is configured to provide a preset temperature for the biochemical reactions; the transfer module 2 is configured to transfer the samples; and the control module 4 is configured to control the coordinated operation of the transfer module 2 and the incubation module 3. The sample processing system 100 can be used to perform operations such as transfer, mixing, separation, purification, and incubation reactions on samples. The samples may include, for example, biological samples required for biochemical analysis (such as human blood, tissue, or saliva samples), adapters, reagents used for biochemical analysis, and other liquid samples; sample carriers (such as magnetic beads) used to carry biological samples in sequencing library construction; or a mixture of biological samples, reagents, and sample carriers, but is not limited thereto.

[0049] Specifically, the sample processing system 100 can perform operations such as transferring, mixing, separating, and purifying the sample, and incubate it through the incubation module 3. Incubation can be simply to bring the sample to a specific temperature, or it can cause the biological sample to undergo a biochemical reaction to form a reaction product. In this case, the sample processing system 100 can also include a detection and quantification module 8, which can detect and quantify the obtained reaction products. For example, in the embodiment of the present application, the sample processing system 100 can realize the automated preparation of a single-molecule sequencing library. The obtained reaction products can be detected and quantified by the detection and quantification module 8 (which can be a fluorescence quantitative detection module), and finally the obtained library can be used for subsequent sequencing.

[0050] Please refer to Figures 3 to 5 in conjunction with each other. The storage module 1 includes a consumable carrier 11, which includes multiple functional areas. In some embodiments, the multiple functional areas include a first type of area and a second type of area. The first type of area has multiple first through holes 12, and the second type of area has multiple second through holes 13. The hole depth of the first through hole 12 is less than the hole depth of the second through hole 13. The first through hole 12 and the second through hole 13 are configured to place different consumables. Specifically, the first through hole 12 can be used to place the first type of consumables. The first type of consumables can be containers for loading samples, such as reaction containers 10 for loading biological samples and reagent containers 20 for loading reagents, etc. Specifically, they can be tubular containers, such as sample tubes, centrifuge tubes, reagent bottles, etc. The second through hole 13 can be used to place the second type of consumables. The second type of consumables can be pipette tips 30 used for liquid transfer in conjunction with a pipette.

[0051] In some embodiments, the first type of area includes: a sample area 101, a transfer area 102, a processing area 103, a product area 104, and a reagent area 105. The sample area 101 may include at least one first through-hole 12 for placing a reaction vessel 10 loaded with a biological sample. The transfer area 102 may include at least one first through-hole 12 for temporarily storing a reaction vessel 10 loaded with a biological sample or an empty reaction vessel 10. The processing area 103 may include at least one first through-hole 12 for placing a reaction vessel 10 loaded with a mixed sample, wherein the mixed sample may be subjected to a mixing operation or a separation and purification operation in the processing area 103. The product area 104 may include at least one first through-hole 12 for placing a reaction vessel 10 loaded with a reaction product. The reagent area 105 may include at least one first through-hole 12 for placing a reagent container 20 loaded with a reagent. Specifically, the reaction container 10 can be a container of the same or similar structure, such as a sample tube or centrifuge tube, and the reagent container 20 can be a reagent tube specifically for holding reagents. It is understood that the reaction container 10 can be used to hold reagents, but is not specifically for loading reagents. The interiors of the reaction container 10 and the reagent container 20 are used to load samples. The volumes of the reaction container 10 and the reagent container 20 can be selected based on the sample size. The diameters of the corresponding first through holes 12 are designed based on the outer diameters of the reaction container 10 and the reagent container 20. The depth of the first through holes 12 is preferably sufficient to stably secure the reaction container 10 and the reagent container 20.

[0052] In some embodiments, the sample area 101, the transfer area 102, the processing area 103, the product area 104 and the reagent area 105 all include a plurality of first through holes 12, which can process multiple times of samples at the same time, thereby increasing the amount of sample processing, and can also process different samples at the same time to improve sample processing efficiency. In some embodiments, during a biochemical reaction (such as library construction), the volume of a single reaction vessel 10 determines the amount of a single reaction system, and the consumable carrier 11 can be compatible with reaction vessels 10 of different volumes, and can cover the consumable requirements of microliter to milliliter levels. For example, in this embodiment, when the volume of a single reaction vessel 10 is 1.5 mL, the amount of sample added is 2 / 3 of the reaction vessel 10. At this time, the single reaction system can reach 1 mL, which can effectively increase the amount of the reaction product (such as the preparation amount of the library).

[0053] In some embodiments, the sample area 101, the transfer area 102 and the product area 104 are all provided with identification marks to facilitate distinction and convenient placement of the reaction vessel 10. The processing area 103 will only be used during the sample processing process, and an identification mark may not be provided. It is understandable that the identification marks corresponding to the sample area 101, the transfer area 102 and the product area 104 may be the same or different. Specifically, the identification mark may be an identification groove 14 respectively provided in the sample area 101, the transfer area 102 and the product area 104. For example, each identification groove 14 may be an annular groove surrounding all the first through holes 12 of the corresponding area to separate the sample area 101, the transfer area 102 and the product area 104, so that the consumables in an annular identification groove 14 can be easily identified as having the same function.

[0054] As shown in Figures 4 to 6, the reaction container 10 or reagent container 20 placed in the first through hole 12 is used to hold the sample internally, and the sample will not be contaminated on the outside. Therefore, the hole depth H1 of the first through hole 12 should be sufficient to stably fix the corresponding container and does not need to be too thick. To this end, the portion of the consumable carrier 11 corresponding to the first type of area is designed as a hollow structure, which is conducive to reducing the weight of the consumable carrier 11. In addition, it is also convenient for the installation of other modules in the sample processing system 100 to improve space utilization. In some embodiments, the processing area 103 has an installation cavity 15, which is part of the hollow structure. According to the function of the processing area 103, the installation cavity 15 can be used to accommodate the second mixing module or separation and purification module mentioned later.

[0055] As shown in Figures 3, 4, and 6, the second type of area can be a tip area 109. The tip area 109 includes a plurality of second through-holes 13. The plurality of second through-holes 13 can be used to accommodate a plurality of tips 30. Assuming the length of the tip 30 is H, the depth H2 of the second through-hole 13 is greater than or equal to 1 / 2H. The second type of area can be used to accommodate both unused and used tips 30. Specifically, after a pipette or other liquid handling device is used to transfer a sample with a tip 30, the used tip 30 is inserted into the original second through-hole 13. At this time, residual sample may remain on the outer wall of the used tip 30. By setting the depth H2 of the second through-hole 13 longer, the risk of the tip 30 coming into contact with other tips 30 when being removed from or inserted into the second through-hole 13 can be reduced, thereby reducing the risk of cross-contamination.

[0056] In some embodiments, a removable protective film (not shown) is provided on the surface of the tip area 109 to prevent liquid from the outside of the tips 30 from stained on the tip area 109, thereby facilitating the recycling of the consumable carrier 11. Specifically, the protective film can be provided on the back side of the tip area 109, that is, the surface near the tip of the tip 30 after the tip 30 is placed in the second through-hole 13 of the tip area 109. This prevents liquid from the tip of the used tip 30 from stained on the back side of the tip area 109. It is understood that protective films can also be provided on both the front and back sides of the tip area 109 to prevent liquid from the outside of the tip 30 from stained on the surface of the tip area 109 during the placement of the used tip 30.

[0057] As shown in Figures 3 and 4, according to actual use needs, the reaction container 10 for loading samples can be open or have a sealing cover 40. When the reaction container 10 is a sealed container with a sealing cover 40, the multiple functional areas also include a third type of area, and the third type of area includes a sealing cover temporary storage area 106. The sealing cover temporary storage area 106 has a plurality of grooves 16, and the grooves 16 are configured to temporarily store the sealing cover 40 removed from the reaction container 10. In some embodiments, the sealing cover temporary storage area 106 is arranged at a position close to the sample area 101 and the processing area 103 to facilitate the placement and removal of the sealing cover 40. It can be understood that the part of the consumable carrier 11 corresponding to the third type of area can also be set to a hollow structure to further reduce the weight of the consumable carrier 11.

[0058] As shown in Figures 3 and 4 , the multiple functional areas also include a fourth type of area, including a waste liquid area 107. The waste liquid area 107 includes a waste liquid tank 17, which is configured to accommodate waste liquid generated during sample processing. In some embodiments, the waste liquid tank 17 is provided with a cover plate 171, which is provided with a waste liquid hole 172 that communicates with the waste liquid tank 17. A pipette tip 30 for transferring waste liquid can be inserted into the waste liquid tank 17 through the waste liquid hole 172 to discharge the waste liquid. The cover plate 171 can effectively reduce problems such as aerogel contamination caused by waste liquid splashing.

[0059] As shown in FIG3 , the consumable carrier 11 also includes a marking area 108, which can be used to locate multiple functional areas. In some embodiments, the marking area 108 includes two cross-shaped marking grooves 181. The consumable carrier 11 is generally rectangular, and the two cross-shaped marking grooves 181 are respectively arranged at both ends of a diagonal line of the consumable carrier 11. The two cross-shaped marking grooves 181 can accurately locate each functional area and the placement of specific consumables, thereby improving the accuracy and efficiency of sample transfer.

[0060] As shown in FIG3 , the consumable carrier 11 further includes an identification area on which an identification code 182 is provided, which may be a QR code, for example. Sample information can be obtained by identifying the identification code 182 on the consumable carrier 11 , thereby effectively avoiding sample usage errors.

[0061] In some embodiments, the consumable carrier 11 can be a disposable consumable, eliminating the need for cleaning and reducing cross-contamination caused by reuse. In actual use, simply add the desired sample to a designated location on the consumable carrier 11 to begin the fully automated sample processing process. It is understood that the consumable carrier 11 can also be recycled.

[0062] In some embodiments, the consumable carrier 11 is an integrated structure that integrates multiple functional areas into an integrated structure, which can effectively improve space utilization. Moreover, different consumables are integrated on the same consumable carrier 11 for transfer, and one-stop consumable loading avoids the time loss of repeated loading, optimizes the process, simplifies the operation, and is more efficient. In addition, the integrated consumable carrier 11 can replace multiple customized carriers, improve resource utilization, and reduce R&D investment costs. According to the amount of different consumables used and the convenience of the path for transferring consumables during use, the aforementioned functional areas can be reasonably arranged in a certain manner to maximize space utilization, while making the path for consumable transfer shorter and the operation simplest. In some embodiments, the sample area 101, transfer area 102, processing area 103, and product area 104 in the first-type area are centralized together to facilitate sample processing and shorten travel time. For example, the sample area 101 and processing area 103 are arranged side by side, and the transfer area 102 and product area 104 are arranged side by side, with the transfer area 102 adjacent to the sample area 101 and the product area 104 adjacent to the processing area 103. The third-type area is located adjacent to the first-type area. Specifically, the sealing cap temporary storage area 106 is located adjacent to the sample area 101 and processing area 103, facilitating the removal and placement of the sealing cap 40 and shortening travel time. The second-type area is also located adjacent to the first-type area. Specifically, the tip area 109 is located adjacent to the transfer area 102 and product area 104, facilitating the removal and placement of the tips 30 during sample processing. The reagent area 105 in the first-type area can be located adjacent to the tip area 109 in the second-type area. This allows installed tips 30 to be moved directly to the reagent area 105 for reagent removal, shortening travel time. The waste liquid area 107 can be set relatively far away from the first type of area to prevent waste liquid from contaminating the sample. Specifically, the waste liquid area 107 is set near the reagent area 105. It can be understood that the different functional areas on the consumable carrier 11 can also be increased or decreased, or the position can be changed according to actual needs.

[0063] It can be understood that in other embodiments, the consumable carrier can also include multiple independent carrier units, each carrier unit has at least one functional area. By reasonably designing the functional areas, consumables that need to be set close to each other can be designed on the same carrier unit. On the premise of easy operation, the space of the sample processing system 100 can also be reasonably utilized.

[0064] Please refer to Figure 2 again. The storage module 1 also includes a carrier carrying device 19, which can be an electric drawer. The consumable carrier 11 can be detachably mounted on the carrier carrying device 19. The opening and closing of the carrier carrying device 19 can be controlled by the control module 4 to facilitate the removal and loading of the consumable carrier 11.

[0065] According to actual needs, existing containers for loading samples can be placed on the consumable carrier 11, or containers of specific shapes and sizes can be customized. As shown in Figure 7, in some embodiments, the storage module 1 also includes a reaction container 10 for loading samples, and the reaction container 10 includes a first cavity 101' and a second cavity 102' that are interconnected and connected. The inner diameter of the second cavity 102' is smaller than the inner diameter of the first cavity 101', and the inner diameter of the second cavity 102' decreases in the direction away from the first cavity 101', thereby forming a conical container with a stepped structure. In addition, in the selection of the material of the reaction container 10, in addition to considering the chemical compatibility with the reagent, it is also necessary to ensure that the inner surface of the reaction container 10 has low adsorption to the biological sample, so as to reduce the risk of loss of the biological sample and ensure that the biological sample will not be lost accidentally.

[0066] Please refer to Figures 2 to 4 together. The transfer module 2 includes a transfer device 22 and a pipette device 21. The transfer device 22 is used to transfer the reaction vessels 10 on the consumable carrier 11 as a whole between different areas during the sample processing process, which can effectively reduce the risk of cross-contamination and improve the accuracy of the ratio of different samples, thereby improving the effectiveness of sample processing. The pipette device 21 can be used to transfer samples. Specifically, the pipette device 21 can cooperate with the pipette tip 30 in the aforementioned pipette tip area 109 to transfer liquid samples. For example, the pipette device 21 and the pipette tip 30 can be used to add or aspirate samples into the reaction vessel 10.

[0067] In some embodiments, the transfer device 22 may include a robotic arm 23 and a rotating jaw assembly 24 provided on the robotic arm 23. The robotic arm 23 is configured to drive the rotating jaw assembly 24 to move in multiple directions. The rotating jaw assembly 24 can perform rotational motion in multiple directions to grasp or release the reaction container 10. In some embodiments, the pipetting device 21 may be integrated on the robotic arm 23. Specifically, the robotic arm 23 includes a three-dimensional controller, an X' direction motion controller, a Y' direction motion controller, and two Z direction motion controllers. Among them, the X' direction motion controller can control the movement of the rotating jaw assembly 24 and the pipetting device 21 in the X' direction, the Y' direction motion controller can control the movement of the rotating jaw assembly 24 and the pipetting device 21 in the Y' direction, and the two Z direction motion controllers are used to respectively control the movement of the rotating jaw assembly 24 and the pipetting device 21 in the Z direction. In this embodiment, the rotating clamping jaw assembly 24 has two functions, namely, clamping and rotating, which can realize the in-situ rotation of the reaction vessel 10, the transfer of the reaction vessel 10 between modules, and the opening and closing of the cover of the reaction vessel 10, and the clamping torque and the rotational torque can be flexibly adjusted within a certain range. In this embodiment, the pipetting device 21 can adopt an air plunger pipetting pump. The pipetting pump is combined with a disposable suction tip 30 to effectively avoid cross contamination and has a suction tip detection function. In addition, the pipetting device 21 is integrated with a pressure sensor to effectively detect reagent blockage and empty suction problems. The above-mentioned direction controllers in this embodiment all adopt closed-loop control, have no cumulative coordinate error, and have a torque detection function. In the event of a collision failure, the machine can automatically stop and alarm.

[0068] As shown in Figures 1 and 2 to 4, when the reaction container 10 has a sealing cover 40, the sample processing system 100 further includes a cover opening and closing module 7, which includes the aforementioned transfer device 22 and a fixed clamping device 71. The fixed clamping device 71 is configured to fix the reaction container 10, and the transfer device 22 is further configured to cooperate with the fixed clamping device 71 to open or close the sealing cover 40 on the reaction container 10. Specifically, the robot arm 23 drives the rotating clamping assembly 24 to grab the reaction container 10 to the fixed clamping device 71, and the fixed clamping device 71 closes and clamps the reaction container 10. Then, the rotating clamping assembly 24 rotates and rises to open the sealing cover 40, and then places the sealing cover 40 into the groove 16 of the sealing cover temporary storage area 106 corresponding to the consumable carrier 11. Then, the reaction container 10 is removed from the fixed clamping device 71 and transferred to the next station.

[0069] Referring to Figures 8 and 9 , the incubation module 3 can be used to heat, cool, and maintain the temperature of reactants during biochemical reactions. For example, it can be used to incubate biochemical substances during gene sequencing. "Incubation" refers to creating the required temperature conditions for the biochemical reactions of the biochemical substances through heating, cooling, and maintaining the temperature. The incubation module 3 includes a base 31, a heat sink 32 disposed on the base 31, and a heating device 33 disposed on the heat sink 32. The heating device 33 includes a temperature control structure 331 and a heating seat 332 disposed on the temperature control structure 331. The heating seat 332 has at least one heating groove 333. The heating groove 333 can be used to accommodate a reaction vessel 10 containing a sample. The temperature control structure 331 can regulate the temperature of the heating groove 333 to ensure that the sample in the reaction vessel 10 reaches a preset temperature, thereby providing the required temperature conditions for the sample's biochemical reaction. Among them, the inner wall 334 of the heating groove 333 has a contoured structure corresponding to the outer wall of the reaction vessel 10, that is, the shape of the inner wall 334 of the heating groove 333 is designed to be roughly the same as the shape of the outer wall of the reaction vessel 10. By contouring the inner wall 334 of the heating groove 333, the inner wall 334 can be more closely fitted to the outer wall of the reaction vessel 10, increasing the contact area between the heating groove 333 and the reaction vessel 10, thereby improving the heat conduction efficiency. At the same time, this contoured design will also make the heating of the sample in the reaction vessel 10 more uniform, which is more conducive to the incubation of the sample.

[0070] Please refer to Figure 9 in conjunction with the figure. Temperature control structure 331 can be a thermoelectric cooler (or semiconductor cooler, TEC). TECs are characterized by being quiet, vibration-free, refrigerant-free, compact, and lightweight. They also offer reliable operation, easy operation, rapid cooling and heating, and highly precise temperature control. Temperature control structure 331 includes a first surface 3311 and a second surface 3312 positioned opposite each other. First surface 3311 is positioned adjacent to heating base 332, while second surface 3312 is positioned adjacent to heat sink 32. During heating, first surface 3311 serves as the hot surface, while second surface 3312 serves as the cold surface. During cooling, first surface 3311 serves as the cold surface, while second surface 3312 serves as the hot surface.

[0071] The inner wall 334 of the heating groove 333 is designed to imitate the shape of the outer wall of the reaction vessel 10. In this embodiment, as shown in Figure 10, the reaction vessel 10 is roughly a conical structure, so the inner wall 334 of the heating groove 333 is also designed to be a conical structure in order to fit more closely with the outer wall of the reaction vessel 10. In some embodiments, along the depth direction h of the heating groove 333, the heating groove 333 includes a first groove 336, a second groove 337 and a third groove 3371 which are connected in sequence. The inner diameter L2 of the second groove 337 and the inner diameter L3 of the third groove 3371 are both smaller than the inner diameter L1 of the first groove 336, and the inner diameter L2 of the second groove 337 decreases in the direction away from the first groove 336, so that the second groove 337 forms a tapered groove structure, and the inner diameter L3 of the third groove 3371 is roughly equal to the inner diameter of the end of the second groove 337 away from the first groove 336, so that the side wall of the third groove 3371 is roughly perpendicular to the bottom, and finally the first groove 336, the second groove 337 and the third groove 3371 form a tapered stepped groove. This stepped groove design facilitates the mass production of the heating groove 333. At the same time, this contoured design will also make the heating of the sample in the reaction vessel 10 more uniform, which is more conducive to the incubation of the sample. It can be understood that in other embodiments, the heating groove may also include a first groove and a second groove that are interconnected, wherein the inner diameter of the first groove is larger than the inner diameter of the second groove, and the inner diameter of the second groove decreases successively in the direction away from the first groove, so that the second groove forms a conical groove structure. This conical second groove can better fit the outer wall of the conical container.

[0072] In some embodiments, according to the tapered structure of the reaction container 10 , the taper of the second groove 337 of the heating groove 333 is substantially the same as the taper of the reaction container 10 .

[0073] The heating seat 332 includes a heating base 3321 arranged on the side of the temperature control structure 331 away from the heat dissipation device 32 and at least one heating groove body 3322 arranged on the side of the heating base 3321 away from the temperature control structure 331. The heating groove 333 is formed on the heating groove body 3322. The temperature control structure 331 is clamped between the heating base 3321 and the heat dissipation device 32. By fixing the heating base 3321 and the top of the heat dissipation device 32 together, the temperature control structure 331 can be clamped, thereby making the temperature control structure 331 in close contact with the heat dissipation device 32 and the heating base 3321.

[0074] In some embodiments, the heating base 3321 and the heating tank 3322 can be an integrally formed structure to improve the efficiency of heating and cooling. For example, the heating base 332 is a metal bath made of metal.

[0075] In some embodiments, the heating tank 333 extends to the heating base 3321, effectively increasing the depth of the heating tank 333, fully utilizing the space within the heating base 3321, and placing the heating tank 333 closer to the temperature control structure 331, further improving heating and cooling efficiency. In this embodiment, the heating tank 333 can accommodate reaction vessels 10 with milliliter-level volumes, thereby effectively increasing sample incubation throughput.

[0076] In some embodiments, the distance between the bottom of the heating groove 333 and the surface of the temperature control structure 331 close to the heating base 3321 is between 2 mm and 4 mm, which can keep the heating and cooling rate within a reasonable range, so as not to affect the biochemical reaction too fast or too slow to affect the heating and cooling efficiency.

[0077] In some embodiments, the heating base 3321 is provided with a plurality of heating slots 3322, each of which has a heating slot 333. A gap exists between adjacent heating slots 3322, allowing the plurality of heating slots 3322 to be independently disposed. This allows the overall heating base 332 to form a hollow structure, thereby reducing the weight of the heating device 33 by approximately half compared to a non-hollow design. Furthermore, the hollow design shortens the heating and cooling time, thereby reducing the energy consumption of the incubation module 3.

[0078] Please refer to Figures 9, 11, and 12 together. When the heating device 33 and the heat sink 32 are installed, the heating base 332 is directly connected to the top of the heat sink 32 via screws. Specifically, steps 338 are provided on opposite sides of the heating base 3321. The steps 338 are provided with a first connection hole 339. The steps 338 are provided with a heat insulating block 35. The heat insulating block 35 has a boss 351 on the side near the step 338. The boss 351 can extend into the first connection hole 339. The boss 351 has a second connection hole 352, which is provided through the heat insulating block 35. When fixing the heating base 332 to the top of the heat sink 32, place the insulation block 35 on the step 338, and allow the boss 351 to extend into the first connection hole 339. Then, pass the connecting piece (such as a screw) through the second connection hole 352 of the insulation block 35 and the hole at the top of the heat sink 32 to fix the heating base 3321 to the heat sink 32. At the same time, due to the connection between the top of the heat sink 32 and the heating base 332, the temperature control structure 331 is clamped and fixed in the middle. By arranging the insulation block 35 on the heating base 3321, since the boss 351 extends into the first connection hole 339, a certain gap can be formed between the connecting piece and the hole wall of the first connection hole 339, so that the connecting piece will not directly contact the heating base 3321, thereby avoiding heat loss caused by direct contact between the heating piece and the heating base 332. Among them, the insulation block 35 can be made of insulation material.

[0079] As shown in Figure 9, the heating device 33 also includes a temperature sensor 335. The temperature sensor 335 is arranged on the heating device 33, specifically on the heating base 3321, so as to monitor the temperature changes of the heating seat 332 and the heating tank 333, and feed back the temperature to the control module 4 in real time, and has the function of monitoring and feeding back the temperature.

[0080] Please refer to Figures 8, 9 and 11 again. The incubation module 3 also includes a heat shield 34 that is sleeved on the outside of the heating device 33. The heat shield 34 wraps the entire heating seat 332, isolates the contact between the air and the heating seat 332, and plays a role in isolating heat radiation and preventing the formation of condensed water. It can be understood that the heat shield 34 is provided with a mounting hole 341 at the position corresponding to the heating tank 333, so that the reaction vessel 10 can be installed in the heating tank 333. The side wall of the mounting hole 341 at one end away from the heat sink 32 protrudes toward the inside of the mounting hole 341 to form a protrusion 342. The protrusion 342 is provided corresponding to the end face of the heating tank 333 away from the heat sink 32 to cover the end face of the heating tank 333. Specifically, the protrusion 342 is located at the end of the heating tank body 3322 away from the heat sink 32 to isolate the heating device 33 from the outside air to the greatest extent. In addition, when the reaction container 10 extends into the heating tank 333 from the mounting hole 341 , the end of the reaction container 10 can further enhance the effect of isolating the heating tank 333 from the outside.

[0081] During use, as shown in Figures 8 and 9 , a reaction vessel 10 containing a sample (e.g., a biological sample for library preparation) is placed into the heating tank 333 of the incubation module 3. The sample volume is approximately 1 / 3 to 2 / 3 of the reaction vessel 10's volume. At this point, the sidewalls of the reaction vessel 10 are in contact with the inner wall 334 of the heating tank 333. The bottom of the reaction vessel 10 is approximately 2 mm to 4 mm from the first surface 3311 of the temperature control structure 331. The sample in the reaction vessel 10 is completely buried in the heating tank 333. The incubation module 3 begins heating. At this point, the first surface 3311 of the temperature control structure 331 serves as the hot surface, while the second surface 3312 serves as the cold surface. The hot surface of the temperature control structure 331 transfers its temperature to the library preparation sample in the reaction vessel 10 through the heating base 332. The cold surface of the temperature control structure 331 transfers its temperature to the heat sink 32, which further dissipates the heat. A temperature sensor 335 monitors temperature changes in the heating base 332 and heating tank 333. When the temperature reaches the preset temperature, the temperature control structure 331 maintains a constant temperature and the sample begins to be incubated.

[0082] After the set incubation time has expired, the incubation module 3 begins cooling. At this point, the first surface 3311 of the temperature control structure 331 becomes the cold surface, while the second surface 3312 becomes the hot surface. The cold surface of the temperature control structure 331 transmits its temperature to the sample in the reaction vessel 10 via the heating base 332. The hot surface of the temperature control structure 331 transmits its temperature to the heat sink 32, which dissipates the heat. After the set cooling time has expired, the reaction vessel 10 is removed.

[0083] It is understandable that the sample processing system 100 may also include multiple incubation modules 3, and multiple incubation modules 3 may execute multiple temperature intervals. The temperature of the incubation process is usually divided into multiple temperature intervals between 2°C and 99°C, such as a low temperature interval, a medium temperature interval, and a high temperature interval. If a single incubation module 3 is used, a rapid temperature rise and fall process is usually required for different temperature intervals. Obviously, the performance requirements of the incubation module 3 are higher. In this embodiment, multiple incubation modules 3 are used, and each incubation module 3 executes a temperature interval. Specifically, when the reaction system needs to be quickly heated and cooled, different incubation modules 3 can be set to the corresponding temperature intervals in advance, and then the transfer device 22 is used to clamp the reaction vessel 10 to the corresponding incubation module 3. This can effectively solve the problem of insufficient reagent heating and cooling rate. Compared with a single incubation module 3, the power of the temperature control structure (such as TEC) can be greatly reduced, the convenience and reliability of the temperature control structure selection are improved, and the service life of the incubation module 3 is extended. In addition, there is no need to wait for the heating and cooling process, which can further improve the efficiency of sample processing.

[0084] Please refer to Figures 13 and 14 together. The sample processing system 100 also includes a first mixing module 5. The first mixing module 5 is configured to mix the samples, which can achieve uniform mixing of the samples, can mix at least two samples, and can also homogenize one sample. During the sample processing process, the first mixing module 5 can be used to achieve uniform mixing of the mixture in any scenario where mixing is required. For example, when precipitation occurs in the same biological sample, the first mixing module 5 can be used to mix it evenly. When magnetic beads are added to the biological sample, the first mixing module 5 can also be used to achieve sufficient contact and mixing between the magnetic beads and the biological sample. When reagents are added to the biological sample, the first mixing module 5 can also be used to mix. The first mixing module 5 can also be used to mix two or more reagents, or to mix the biological sample with the reagent, etc.

[0085] The first mixing module 5 includes a support base 51 and a mixing device 52 provided on the support base 51. The mixing device 52 can generate a rotational force in a single direction, thereby driving the reaction vessel 10 to rotate in a single direction. By driving the reaction vessel 10 to rotate through the mixing device 52, the mixing efficiency and mixing effect can be effectively improved compared to the suction-and-spit mixing method. Moreover, the reaction vessel 10 can be airtight during the mixing process, effectively reducing the risk of cross-contamination of samples. It is understandable that the mixing device 52 can also generate a rotational force in both positive and negative directions, thereby driving the reaction vessel 10 to rotate in both positive and negative directions, further improving the mixing efficiency and mixing effect. In some examples, in order to reduce the risk of the reaction vessel 10 accidentally escaping from the mixing device 52 during rotation, the first mixing module 5 also includes a blocking device 53, thereby improving the safety of mixing and avoiding problems such as cross-contamination and mixing of samples.

[0086] The support base 51 includes a base 511 , a support frame 512 provided on the base 511 , and a mounting base 513 provided on the support frame 512 . The mixing device 52 and the blocking device 53 are both installed on the mounting base 513 .

[0087] In some embodiments, the mounting base 513 includes a driving member mounting base 514 , a rotating mounting base 515 disposed on the driving member mounting base 514 , and a rotating mounting plate 516 disposed on the rotating mounting base 515 .

[0088] Referring to Figures 1, 15, and 16 , the mixing device 52 includes a mixing drive 521 mounted on a support base 51, a rotating assembly 522 mounted on the support base 51 and connected to the mixing drive 521, and a detector 523. The rotating assembly 522 has a placement slot 524 for placing the reaction vessel 10. Specifically, the mixing drive 521 is mounted on a drive mount 514. The rotating assembly 522 is mounted on a rotating mount 515 and connected to the mixing drive 521. The placement slot 524 on the rotating assembly 522 extends through a rotating mounting plate 516 to facilitate placement of the reaction vessel 10. The detector 523 is mounted on the rotating mount 515 and is positioned corresponding to the rotating assembly 522.

[0089] The mixing drive 521 is configured to generate a rotational force, thereby driving the rotation assembly 522 to rotate, further rotating the reaction vessel 10 located in the placement slot 524 to mix the sample within the reaction vessel 10. Specifically, the mixing drive 521 can drive the rotation assembly 522 to rotate in a single direction. For example, the mixing drive 521 can generate a rotational force along a first direction X or a second direction Y, thereby driving the reaction vessel 10 to rotate in the first direction X or the second direction Y. The mixing drive 521 can also drive the rotation assembly 522 to rotate in both positive and negative directions. For example, the mixing drive 521 can sequentially generate a rotational force along a first direction X and a second direction Y, thereby driving the reaction vessel 10 to rotate in the first direction X and the second direction Y, respectively, with the second direction Y being opposite to the first direction X. The detector 523 can detect the rotational state of the rotation assembly 522 and transmit a signal to the control module 4, thereby controlling the reset of the mixing drive 521. Specifically, the mixing drive 521 needs to be reset after startup or when an abnormality occurs in the mixing device 52.

[0090] In some embodiments, the hybrid drive 521 can provide a linear rotational force along the first direction X and / or the second direction Y, and the rotation component 522 can convert the linear rotational force into an eccentric rotational force, and then convert the linear rotational motion into an eccentric rotational motion, so as to drive the reaction container 10 to perform an eccentric rotational motion along the first direction X and / or the second direction Y.

[0091] In some embodiments, the hybrid drive element 521 can be a motor that uses closed-loop control to achieve high speed and high precision control. It is understood that other drive forms, such as a stepper motor or a combination of a stepper motor and a synchronous belt, can also be used to achieve closed-loop control.

[0092] Referring to Figures 17 and 18 , the rotation assembly 522 may include a sample rotation component 5221, a first connecting component 5222, a second connecting component 5224, and a drive shaft 5225. The sample rotation component 5221 has a hollow cavity in its center, which forms a placement slot 524 for accommodating the reaction vessel 10. The first connecting component 5222 and the second connecting component 5224 are respectively disposed at opposite ends of the sample rotation component 5221. The first connecting component 5222 is mounted on the support base 51. Specifically, the first connecting component 5222 may be mounted on the rotation mounting base 515 (e.g., a bearing seat) of the support base 51. The second connecting component 5224 is connected to the drive shaft 5225, which is connected to the output shaft of the hybrid drive 521. The axis of the drive shaft 5225 is parallel to and does not overlap with the axis of the hybrid drive 521. The rotating assembly 522 also includes a bearing (e.g., a deep groove ball bearing 5226) for securing the drive shaft 5225. The shaft of the drive shaft 5225 passes through the deep groove ball bearing 5226 and is restrained by a shoulder. The deep groove ball bearing 5226 is mounted on the driver mounting seat 514. The sample rotating component 5221 is also provided with a retaining spring 5223. The retaining spring 5223 is located at one end of the first connecting component 5222 near the second connecting component 5224. The sample rotating component 5221 is rotationally restrained by the first connecting component 5222, the second connecting component 5224, and the retaining spring 5223. In some embodiments, the sample rotating component 5221 can be a sample rotating shaft, and the first connecting component 5222 and the second connecting component 5224 are both spherical bearings.

[0093] Specifically, the first connecting part 5222 and the second connecting part 5224 both include a rotating part (or rotor) and a fixed part (or stator) that are movably connected. The axis of the sample rotating part 5221 coincides with the axis of the rotating part of the first connecting part 5222 and the axis of the rotating part of the second connecting part 5224. The axis of the fixed part of the first connecting part 5222 coincides with the axis of the mixing drive 521. The axis of the fixed part of the second connecting part 5224 coincides with the axis of the drive shaft 5225. The axis of the placement slot 524 coincides with the axis of the sample rotating part 5221. In this way, the axis of the reaction container 10 located in the placement slot 524 can roughly coincide with the axis of the sample rotating part 5221. As shown in Figures 18 and 19, the driving shaft 5225 can be an eccentric rotating shaft. The axis of the driving shaft 5225 is parallel to and does not overlap with the axis of the mixing drive component 521. At this time, the driving shaft 5225 has two rotation center lines a1 and a2. There is a certain distance A1 between the two rotation center lines a1 and a2. The distance A1 can determine the deflection amplitude of the sample rotating component 5221. The driving shaft 5225 with a large eccentric distance A1 can be determined based on the actual oscillation amplitude of the reaction container 10 required. Thus, the linear drive of the mixing drive element 521 can drive the drive shaft 5225 to rotate eccentrically. During the process of rotating the sample rotating component 5221, the drive shaft 5225, because the axis of the drive shaft 5225 is parallel to and does not overlap the axis of the mixing drive element 521, causes the sample rotating component 5221 to deviate by a certain angle α under the drive shaft 5225. This generates an eccentric force, which causes the reaction vessel 10 located in the placement slot 524 to undergo eccentric rotational motion under the action of the eccentric force. The sample in the reaction vessel 10, under the action of the eccentric force, undergoes mixing oscillation, effectively improving the mixing effect. This is particularly beneficial for removing sample aggregated on the sidewalls of the reaction vessel 10 from the sidewalls, thereby achieving uniform mixing between samples. Furthermore, the frequency of the mixing oscillation can be controlled by the rotational speed of the mixing drive element 521, thereby selecting an appropriate mixing oscillation frequency to achieve optimal mixing effect and high mixing efficiency. It can be understood that any mechanical structure that can achieve eccentric rotation can be used as the aforementioned rotating component in the embodiment of the present application, and is not limited to the specific structure of the aforementioned rotating component 522.

[0094] The mixing device 52 also includes a rotation limiting assembly 525, which includes a limiting component 5251 and a stopper 5252. The stopper 5252 is fixed to the support base 51 outside the rotation assembly 522, specifically disposed on the upper surface of the rotation mounting plate 516 and located to the side of the sample rotation component 5221. The limiting component 5251 includes a first end A and a second end B that are oppositely disposed. The first end A is fixed to the rotation assembly 522, and the second end B is movably engaged in a track groove (e.g., a U-shaped track groove) of the stopper 5252. Specifically, the first end A of the limiting component 5251 is fixed to the side wall of the sample rotation component 5221. As the drive shaft 5225 drives the sample rotating component 5221 to rotate, it also drives the limiting component 5251 to move synchronously. After being radially limited by the stopper 5252, the limiting component 5251 can only swing up and down within the U-shaped track groove, thereby restricting the rotational path of the sample rotating component 5221. This allows the sample rotating component 5221 to form an offset angle of ±α, thereby driving the reaction container 10 to form a rotational swing of ±α. By providing the rotation limiting assembly 525, the rotational path of the sample rotating component 5221 can be restricted, achieving an appropriate range of eccentric rotation, thereby achieving better mixing effect and higher mixing efficiency.

[0095] In some embodiments, the rotation limiting assembly 525 further includes a limiting plate 5253, which is disposed on the rotation assembly 522 and located at the edge of the placement slot 524. Specifically, the limiting plate 5253 is disposed on the outer wall of the sample rotating component 5221. When a reaction vessel 10 with a flip cover is placed in the placement slot 524, the limiting plate 5253 can support the open flip cover.

[0096] In some embodiments, the detector 523 may be a photoelectric switch for detecting the rotational state of the drive shaft 5225 to reset the mixing drive 521. This reset is typically performed before a mixing operation or when an abnormality occurs. Specifically, the drive shaft 5225 includes a drive shaft body 52251 and a blocking portion 52252 disposed on the drive shaft body 52251. The blocking portion 52252 has a notch 52253 disposed therein. When the drive shaft 5225 rotates and the blocking portion 52252 rotates into the sensing area of ​​the detector 523, the detector 523 generates a sensing signal. The detector 523 transmits the sensing signal to the controller, which further controls the rotation of the hybrid drive 521, thereby driving the rotation of the drive shaft 5225. As shown in FIG19 , because the axis of the drive shaft 5225 is parallel to and non-coincident with the axis of the hybrid drive 521, the distance A1 between the two rotational centerlines a1 and a2 of the rotating shaft 5225 can cause the sample rotating component 5221 to deflect during rotation, placing the sample rotating component 5221 in an eccentric position. When the notch 52253 on the blocking portion 52252 rotates into the sensing area of ​​the detector 523, the detector 523 no longer senses a signal, and the hybrid drive 21 is reset. The cooperation between the detector 523 and the blocking portion 52252 on the drive shaft 5225 allows the sample rotating component 5221 to be reset.

[0097] 20 and 21 , the blocking device 53 includes a mounting plate 531 disposed on the support base 51, a blocking driver 532 disposed on the mounting plate 531, and a blocking arm 534 disposed on the blocking driver 532. The blocking arm 534 is configured to move under the drive of the blocking driver 532 to enter a blocking state and a non-blocking state. In the blocking state, the blocking arm 534 is driven by the blocking driver 532 to move above the reaction vessel 10 on the mixing device 52. In the non-blocking state, the blocking arm 534 is driven by the blocking driver 532 to move away from the reaction vessel 10 on the mixing device 52. Specifically, the blocking arm 534 includes a connecting end 5341 connected to the blocking driver 532 and a free end 5342 disposed opposite the connecting end 5341. The blocking state is when the free end 5342 of the blocking arm 534 is moved above the placement slot 524 of the mixing device 52, and the non-blocking state is when the free end 5342 of the blocking arm 534 is moved away from the placement slot 524. Specifically, when the blocking arm 534 is driven by the blocking driver 532 to move above the placement slot 524, it can block the reaction vessel 10 in the placement slot 524, preventing the reaction vessel 10 from falling out of the placement slot 524 during the mixing process, which could damage the reaction vessel 10, cause sample loss, and cause cross-contamination. After mixing is complete, the blocking arm 534 is driven by the blocking driver 532 to move away from the placement slot 524, allowing the reaction vessel 10 in the placement slot 524 to be removed.

[0098] In some embodiments, the output end of the blocking drive 532 is provided with a rotating shaft 533, and the connecting end 5341 of the blocking arm 534 is fixed to the rotating shaft 533. The blocking drive 532 drives the blocking arm 534 to rotate to achieve switching between the blocking state and the non-blocking state. It is understood that the blocking device 53 can also adopt other motion forms, such as linear motion, to achieve switching between the blocking state and the non-blocking state of the blocking arm 534, thereby achieving the purpose of blocking the reaction container 10.

[0099] In some embodiments, a blocking member 535 is provided on the free end 5342 of the blocking arm 534. The blocking member 535 is used to block or remove the reaction vessel 10 from the placement slot 524. Specifically, when the blocking arm 534 rotates to the blocking position, the blocking member 535 blocks the end of the reaction vessel 10. After mixing is completed, the blocking drive 532 drives the rotating shaft 533, which in turn drives the blocking arm 534 to rotate to the non-blocking position, thereby removing the blocking member 535 from the reaction vessel 10, thereby facilitating the removal of the reaction vessel 10 from the placement slot 524.

[0100] The blocking device 53 also includes a sensing component 536, which can realize the detection function of the blocking driving member 532 in place and the origin reset detection function. The sensing component 536 includes: a sensor 5361 and a blocking piece 5362. Among them, the blocking piece 5362 is arranged on the output shaft of the blocking driving member 532, and is specifically sleeved on the rotating shaft 533. The blocking piece 5362 includes a blocking portion 5363 and a notch portion 5364 connected in sequence along the circumferential direction. The sensor 5361 is arranged on the mounting plate 531 and corresponds to the blocking piece 5362. When the blocking piece 5362 rotates, the blocking portion 5363 rotates to the sensing area of ​​the sensor 5361. At this time, the sensor 5361 senses the blocking signal of the blocking portion 5363. At this time, the blocking arm 534 is in the blocking state, and mixing can be started. When the blocking piece 5362 rotates and the notch portion 5364 rotates to the sensing area of ​​the sensor 5361, the sensor 5361 does not sense the blocking signal. At this time, the blocking arm 534 is in the non-blocking state, and the reaction container 10 located in the placement slot 524 can be taken out.

[0101] In some embodiments, the sensor 5361 can be a photoelectric switch.

[0102] The blocking device 53 also includes a limiting assembly 537, which includes a limiting post 5371 and two blocking rods 5372. The limiting post 5371 is sleeved onto the output shaft of the blocking driver 532. Specifically, the limiting post 5371 is disposed on the rotating shaft 533 and extends away from the rotating shaft 533. As the rotating shaft 533 rotates, it drives the limiting post 5371 to rotate. The two blocking rods 5372 are disposed on the mounting plate 531 and are located at either end of the travel path L of the limiting post 5371, thereby limiting the rotation range of the limiting post 5371 and limiting the rotation range of the blocking arm 534.

[0103] In some embodiments, the blocking driving member 532 may be a driving motor, or a rotating electromagnet or a rotating cylinder.

[0104] During operation, as shown in Figures 13 and 14, the reaction vessel 10 containing the sample is placed in the placement groove 524 of the mixing device 52, and the blocking driver 532 is activated. The blocking driver 532 rotates and drives the baffle 5362 and the blocking arm 534 fixed on the rotating shaft 533 to rotate. The blocking arm 534 is restricted by the limiting column 5371 and is directly above the reaction vessel 10. After the sensor 5361 detects the blocking signal of the baffle 5362, the blocking arm 534 is in a blocking state (also known as a closed state). Afterwards, the sensor 5361 transmits the light shielding signal to the control module 4, which controls the mixing driver 521 to start, so as to drive the drive shaft 5225 to rotate, so that the sample rotating component 5221 forms a certain angle of rotation and floats, thereby driving the reaction vessel 10 to achieve mechanical oscillation mixing. In addition, the frequency of the mixing oscillation can be adjusted by controlling the rotation speed of the mixing driver 521 to achieve a better mixing effect and higher mixing efficiency.

[0105] As shown in Figure 14, after mixing is complete, the blocking driver 532 rotates the blocking piece 5362 and blocking arm 534 fixed to the rotating shaft 533. Restricted by the limiting post 5371, the notch 5364 of the blocking piece 5362 rotates into the sensing area of ​​the sensor 5361. The sensor 5361 detects no blocking signal, and the blocking arm 534 is now in a non-blocking state (also referred to as an open state). When the blocking arm 534 is in the open state, the reaction vessel 10 can be removed from the placement slot 524, completing the mixing process.

[0106] Please refer to Figures 22 and 23 together. The sample processing system 100 also includes a separation and purification module 6. The separation and purification module 6 includes a first adsorption device 61. The first adsorption device 61 is configured to generate an attractive force, which is used to separate and purify the biological sample in the mixed sample, or to separate and purify the reaction products produced after the biochemical reaction of the sample. Specifically, in the process of separating and purifying the biological sample, a sample carrier (for example, a magnetic bead) that can bind to or capture the biological sample will be placed in the mixed sample in advance. In this way, under the adsorption of the first adsorption device 61, the sample carrier bound to or captured with the biological sample will be adsorbed to a specific position, thereby separating it from other liquids, and then the other liquids will be sucked out. This process is repeated many times to achieve the purpose of separation and purification. The principle of separating and purifying a mixture containing reaction products is similar and will not be described in detail here.

[0107] In some embodiments, when the reaction product or mixed sample is loaded into the reaction vessel 10, the first adsorption device 61 has a first contoured outer wall 62 corresponding to the outer wall of the reaction vessel 10. The first contoured outer wall 62 is configured to fit closely to or be as close to the outer wall of the reaction vessel 10 as possible. Thus, under the attraction of the first adsorption device 61, the sample carrier loaded with the biological sample is adsorbed onto the inner wall of the reaction vessel 10 near the first adsorption device 61. The waste liquid in the reaction vessel 10 is then aspirated out using the aforementioned pipetting device 21 in conjunction with the pipette tip 30. By employing sidewall adsorption of the sample carrier, different sizes of first adsorption devices 61 can be flexibly configured to accommodate different sample volumes. In particular, when the sample volume to be separated and purified is large, the reaction vessel 10 has a greater depth and a larger sidewall area. By employing sidewall adsorption, the sample carrier is brought closer to the first adsorption device 61, significantly improving the efficiency of separation and purification. Moreover, by using the side wall adsorption method, the separated sample carrier that captures the target substance can be adsorbed on the inner wall of the reaction container 10. Compared with adsorption on the bottom of the container, it is convenient to suck out the waste liquid and the sample carrier will not be accidentally sucked out when sucking out the waste liquid.

[0108] In some embodiments, as shown in Figures 23 and 24, the first adsorption device 61 includes a first adsorption seat 63 and at least one first adsorption body 64 detachably disposed on the first adsorption seat 63. The first adsorption body 64 includes an adsorption surface 65, which constitutes part of the first contoured outer side wall 62. The adsorption surface 65 is used to fit the outer side wall of the reaction vessel 10. Specifically, the first adsorption device 61 includes a bottom 66 and a contoured portion 67 located on the bottom 66. The contoured portion 67 has an inclined surface 69, and the inclination angle of the inclined surface 69 can be designed according to the taper of the actual reaction vessel 10. The inclined surface 69 is recessed toward the inner side of the contoured portion 67 to form at least one mounting groove 68. The first adsorption body 64 is located in the mounting groove 68. The adsorption surface 65 of the first adsorption body 64 and the inclined surface 69 of the contoured portion 67 constitute the first contoured outer side wall 62. As previously described, the reaction vessel 10 has a stepped conical structure. Combined with the first adsorption device 61 having a contoured structure, the adsorption surface 65 of the first adsorbent 64 can be more closely aligned with the outer wall of the reaction vessel 10, effectively shortening the distance between the first adsorbent 64 and the sample carrier within the reaction vessel 10. This can in turn shorten the adsorption time during the separation and purification process, improving both sample processing and adsorption effects. Furthermore, the conical structure of the reaction vessel 10 can effectively increase the liquid level of the eluent, allowing the sample carrier to be completely covered by the eluent, while also reducing the problem of residual waste liquid.

[0109] In some embodiments, multiple mounting grooves 68 can be set on the inclined surface 69 of the first adsorption seat 63, and then multiple first adsorption bodies 64 can be set. In conjunction with the multiple first through holes 12 of the aforementioned processing area 103, samples in multiple reaction containers 10 can be separated and purified at the same time, thereby improving the efficiency of separation and purification.

[0110] In some embodiments, the first adsorption device 61 may be a magnetic frame, and the first adsorption body 64 may be a magnet. Here, a neodymium magnet with a large magnetic flux may be selected to improve the magnetic attraction efficiency.

[0111] As shown in Figures 22 to 24, and in conjunction with Figures 3 and 5, during the separation and purification process, the reaction vessel 10 needs to be close to the side of the first adsorption device 61. In this embodiment, by designing a processing area 103 on the aforementioned consumable carrier 11, and providing a mounting cavity 15 at a position corresponding to the first through-hole 12 in the processing area 103, the first adsorption device 61 of the separation and purification module 6 can be installed in the mounting cavity 15. Specifically, the first adsorption seat 63 is installed in the mounting cavity 15 and is located on the side of the first through-hole 12. The inclined surface 69 of the first adsorption seat 63 is close to the first through-hole 12, and the first adsorption body 64 is embedded in the mounting groove 68 formed on the inclined surface 69, so that the adsorption surface 65 is roughly flush with the inclined surface 69. The reaction vessel 10 containing the mixture to be separated is placed in the first through hole 12 of the processing area 103. The top of the reaction vessel 10 is stuck on the hole wall of the first through hole 12. The side wall of the lower end of the reaction vessel 10 is just close to (or can be directly attached to) the adsorption surface 65 and the inclined surface 69. Since the adsorption surface 65 and the inclined surface 69 have a structure that is anti-shaped with the outer wall of the reaction vessel 10, for example, the lower end of the reaction vessel 10 is conical, and the inclination of the inclined surface 69 at the top of the first adsorption seat 63 is basically the same as the taper of the reaction vessel 10, the outer wall of the reaction vessel 10 can be closely attached to the adsorption surface 65 of the first adsorption body 64. Through the cooperation of the consumable carrier 11 and the separation and purification module 6, the reaction vessel 10 can be brought closer to the first adsorption device 61, and side wall adsorption can be achieved, and the adsorption efficiency is higher.

[0112] It is understandable that the sample processing system 100 may also include other required functional modules, such as an air filtration module.

[0113] Referring to FIG. 22 , in conjunction with FIG. 1 and FIG. 2 , control module 4 includes a control interface 41 and an embedded control chassis 42. Control interface 41 can control a single functional module or provide one-touch control based on a preset logic sequence, offering flexible operation. The use of an embedded electronic control system eliminates the need for an external computer, reducing the overall size of sample processing system 100. This solution offers a simple technical solution, convenient operation, and low cost.

[0114] Please refer to Figures 1, 2 and 22 again. The sample processing system 100 also includes a machine 9 and a housing 91. The above storage module 1, transfer module 2, incubation module 3, control module 4, first mixing module 5, separation and purification module 6, switch cover module 7 and detection and quantification module 8 are all arranged on the machine 9 and located in the housing 91. The relative positions of the above modules are arranged according to the convenience of actual operation. Among them, the transfer module 2 is arranged on one side edge of the machine 9, and the robotic arm 23 can drive the rotating clamping assembly 24 and the pipetting device 21 to move above the machine 9. The incubation module 3 can be set at a position close to the transfer module 2 to facilitate the incubation operation. The first mixing module 5 and the fixed clamping device 71 are arranged between the incubation module 3 and the consumable carrier 11, and the sealing cover temporary storage area 106 on the consumable carrier 11 is arranged close to one side of the fixed clamping device 71 to facilitate the removal and placement of the sealing cover 40. In addition, the control interface 41 of the control module 4 is embedded in the outer side of the housing 91 for easy operation by the staff.

[0115] In some embodiments, as shown in Figure 22, a mounting frame 92 is provided on the machine 9 corresponding to the incubation module 3 and the first mixing module 5. The mounting frame 92 includes a top plate 93 and a side plate 94 located at the periphery of the top plate 93. The top plate 93 and the side plate 94 enclose an installation space, and the incubation module 3 and the first mixing module 5 can be installed inside the installation space. The top plate 93 is located at the top of the incubation module 3 and the first mixing module 5, and the top plate 93 is provided with a plurality of through holes 95, so that the heating tank 333 of the incubation module 3 and the placement tank 524 of the first mixing module 5 can be exposed through the through holes 95 to facilitate the placement and removal of the reaction vessel 10. At the same time, the blocking arm 534 passes through the corresponding through hole 95 and is located above the top plate 93 to facilitate blocking the reaction vessel 10. In some examples, an opening 96 is provided on the side plate 94 to achieve heat dissipation. In addition, the incubation module 3 and the first mixing module 5 are arranged near the control cabinet 42 to facilitate line connection. The incubation module 3 and the first mixing module 5 are integrated and mounted in the mounting frame 92 , thereby improving the aesthetics of the entire sample processing system 100 and helping to reduce the volume of the sample processing system 100 .

[0116] The following further describes each process in the sample processing system 100 .

[0117] Loading process of consumable carrier 11:

[0118] First, remove the consumable carrier 11. This is a disposable item, and common consumables (e.g., common reagents, pipette tips, etc.) are already loaded into the corresponding positions of the consumable carrier 11. Prepare the biological sample by adding it to the sample area 101 of the consumable carrier 11, and add some freshly prepared reagents to the reagent area 105 of the consumable carrier 11. Open the powered carrier loading mechanism 19, place the consumable carrier 11 into the carrier loading mechanism 19, and close the carrier loading mechanism 19 to complete the loading of the consumable carrier.

[0119] Opening process:

[0120] The robotic arm 23 drives the rotating clamp assembly 24 to grab the reaction container 10 to the fixed clamp device 71. The fixed clamp device 71 closes and clamps the reaction container 10. Then the rotating clamp assembly 24 rotates and rises to open the sealing cover 40. The sealing cover 40 is then placed in the groove 16 of the sealing cover temporary storage area 106 corresponding to the consumable carrier 11. The reaction container 10 is then removed from the fixed clamp device 71 and transferred to the next workstation to complete the opening process.

[0121] Closing the lid and mixing process:

[0122] The robotic arm 23 drives the rotating jaw assembly 24 to move to the position of the reaction vessel 10. The rotating jaw assembly 24 grabs the reaction vessel 10 and moves it to the fixed jaw device 71. The fixed jaw device 71 clamps and fixes the reaction vessel 10. The robotic arm 23 drives the rotating jaw assembly 24 to move to the sealing cover temporary storage area 106. The rotating jaw assembly 24 grabs the sealing cover 40 and then moves it to the fixed jaw device 71. The rotating jaw assembly 24 covers the sealing cover 40 on the reaction vessel 10. The rotating jaw assembly 24 grabs the covered reaction vessel 10 and moves it to the first mixing module 5 to start the mixing process. For the specific mixing process, please refer to the working process of the first mixing module 5 mentioned above, which will not be described in detail here.

[0123] Double incubation process:

[0124] For example, if the reaction temperature needs to be raised from 25°C to 70°C, the first incubation module 3 is pre-set to 25°C, and the second incubation module 3 is pre-set to 70°C. The reaction vessel 10 is first placed in the first incubation module 3. When the temperature needs to be changed, the robotic arm 23 drives the rotating gripper assembly 24 to transfer the reaction vessel 10 from the first incubation module 3 to the second incubation module 3. If the temperature needs to be lowered, the reaction vessel 10 is transferred from the second incubation module 3 to the first incubation module 3. This dual incubation process reduces the time required to raise and lower the temperatures of the incubation modules, achieving rapid temperature increases and decreases.

[0125] It is understandable that a single incubation process may also be adopted to implement the temperature rise and fall process through a single incubation module 3. For the specific single incubation process, please refer to the description of the working process of the incubation module 3 above, which will not be elaborated here.

[0126] Aspiration and injection process:

[0127] The robotic arm 23 drives the pipette device 21 to the tip area 109 of the consumable carrier 11. The pipette device 21 is loaded with a pipette tip 30. The robotic arm 23 then drives the pipette device 21 with the pipette tip 30 to aspirate the reagent and add the reagent to the uncapped reaction vessel 10. The pipette device 21 then moves to the tip area 109 and returns the pipette tip 30 to its original position.

[0128] Separation and purification process:

[0129] The robotic arm 23 drives the rotating gripper assembly 24 to grasp the reaction vessel 10, transfer the reaction vessel 10 to the processing area 103 of the consumable carrier 11, and place the reaction vessel 10 in the first through-hole 12 of the processing area 103. The lower sidewall of the reaction vessel 10 is affixed to the sidewall of the first adsorbent 64 of the separation and purification module 6. The first adsorption device 61 is activated to adsorb the sample carrier carrying the biological sample or reaction product in the reaction vessel 10 to the sidewall of the reaction vessel 10. Afterwards, the pipette device 21 is transferred to the tip area 109 of the consumable carrier 11, loaded with a pipette tip 30, and waste liquid in the reaction vessel 10 is aspirated and discharged into the waste liquid tank 17 of the consumable carrier 11. Afterwards, the pipette tip 30 is replaced and an elution reagent is added to the reaction vessel 10 to elute the biological sample or reaction product from the sample carrier, completing the separation and purification process.

[0130] The order of the above processes can be adjusted according to actual needs. Moreover, the opening process, closing the cover and mixing process, and the liquid suction and injection process can be performed multiple times and can be performed in scenarios where opening and closing the cover, mixing, and adding liquid are required.

[0131] Product storage:

[0132] The room temperature storage method is that the reaction products after the sample processing is completed are stored in the product area 104 of the consumable carrier 11. When the sample processing process is completed, the electric carrier carrying device 19 will automatically open and push the consumable carrier 11 out. The experimenter can take the reaction products out of the product area 104 for use in subsequent processes.

[0133] The low-temperature storage method (4°C storage) is suitable for after-get off work or unattended situations. The initial sample processing process is the same in this method, but after the sample processing is completed, the carrier carrying device 19 will not directly push out the consumable carrier 11. Instead, the reaction vessel 10 containing the reaction product in the product area 104 is grabbed by the transfer device 22 to an incubation module 3, and the 4°C refrigeration mode is turned on for long-term storage. When the experimenter needs to take out the reaction product, he only needs to run the "product removal" command, and the transfer device 22 can grab the reaction vessel 10 loaded with the reaction product to the product area 104 of the consumable carrier 11, and then the carrier carrying device 19 will automatically open to push out the consumable carrier 11. The experimenter can take out the reaction product from the product area 104 for use in subsequent processes.

[0134] The sample processing system 100 of the embodiment of the present application has the following beneficial effects:

[0135] (1) The modular design can realize the full process of automated sample processing. The entire process does not require human intervention, which can improve the efficiency and effect of sample processing. It is especially suitable for the automated preparation of single-molecule sequencing libraries. The library has the advantages of high concentration, long fragments and large library volume.

[0136] (2) By integrating the areas for placing different consumables together to form an integrated consumable carrier 11, which occupies less space, the space utilization rate of the sample processing system 100 is significantly improved, and the consumable transfer stroke is reduced, further reducing the volume of the sample processing system 100; different consumables are integrated on the same consumable carrier for transfer, and the consumables are loaded in one stop, which avoids the time loss of repeated loading, optimizes the process, simplifies the operation, and is more efficient; in addition, the integrated consumable carrier 11 can replace multiple customized carriers, improve resource utilization, and reduce R&D investment costs.

[0137] (3) In the incubation module 3, by profiling the inner wall 334 of the heating tank 333, the inner wall 334 of the heating tank 333 can be more closely fitted with the outer wall of the reaction vessel 10, increasing the contact area between the heating tank 333 and the reaction vessel 10, thereby improving the heat conduction efficiency. At the same time, this profiling design also makes the heating of the sample in the reaction vessel 10 more uniform, which is more conducive to the incubation of the sample; the heating seat 332 adopts a hollow design, which is about 1 / 2 smaller than the non-hollow design, with a small heating area, fast heat conduction speed, and effectively shortened heating and cooling time, which is conducive to reducing energy consumption. The incubation module 3 is adapted to the reaction process of a large system. The incubation volume of a single reaction vessel 10 can reach more than 1mL, so it can meet the rapid heating and cooling requirements of large-volume samples that cannot be achieved by traditional incubation modules.

[0138] (4) In the first mixing module 5, closed-loop drive control can be achieved through the mixing device 52, which can ensure high control precision at high speeds. The mixing device 52 can improve the mixing efficiency and mixing effect of the sample through rotational motion. In particular, the mixing device 52 uses centrifugal force to achieve eccentric rotational oscillation of the reaction container 10, which can mix the sample more evenly and have higher mixing efficiency. It can also effectively reduce the risk of sample aggregation on the side wall of the reaction container 10, so as to further improve the mixing effect. It is particularly suitable for mixing magnetic beads and solves the problem of magnetic beads aggregation on the side wall. By setting up a blocking device 53, the risk of the reaction container 10 accidentally escaping from the placement groove 524 during the rotational oscillation process can be effectively reduced, and damage to the reaction container 10 and problems such as sample cross contamination can be prevented. Moreover, the blocking device 53 can be automatically controlled to automatically complete the switching of the blocking arm 534 between the blocking state and the non-blocking state without manual participation. The degree of automation is high, which can further improve the mixing efficiency. The reaction container 10 is a closed container. During the mixing and oscillation process, problems such as sample cross contamination and mixing are effectively avoided.

[0139] (5) In the separation and purification module 6, the consumable carrier 11 cooperates with the separation and purification module 6, so that the reaction vessel 10 can be closer to the first adsorption device 61, and the first adsorption device 61 has an outer wall structure that is shaped like the outer wall of the reaction vessel 10, so that the outer wall of the reaction vessel 10 can be closely fitted with the outer wall of the first adsorption device 61, and side wall adsorption can be achieved, which significantly improves the adsorption efficiency.

[0140] Example 2

[0141] Referring to FIG. 25 , this embodiment provides a sample processing system 200. This sample processing system 200 differs from the aforementioned sample processing system 100 in that the sample processing system 200 does not include a first mixing module. Instead, a separation and purification module 6 is employed in conjunction with a transfer device 22 to achieve sample mixing. The separation and purification module 6 has the same structure as the separation and purification module 6 of the aforementioned embodiment 1. When a sample carrier (e.g., magnetic beads) for adsorbing a biological sample is loaded into a reaction vessel 10, the sample carrier needs to be mixed with the biological sample or a reagent to ensure that the biological sample is fully bound to or captured on the sample carrier, or to ensure that the carrier carrying the biological sample is in full contact with the reagent. The first adsorption device 61 of the separation and purification module 6 is used to generate adsorption force, so that the sample carrier in the reaction container 10 can be adsorbed to the side of the reaction container 10 close to the first adsorption device 61. Then, the reaction container 10 is grabbed by the transfer device 22 and rotated approximately 180 degrees. At this time, the other side of the reaction container 10 is close to the first adsorption device 61. In this way, the sample carrier on one side of the reaction container 10 will quickly disperse and swim toward the side close to the first adsorption device 61. The purpose of operations such as mixing or cleaning can be achieved by relying on the swimming of the sample carrier.

[0142] Example 3

[0143] Referring to Figures 26 and 27 , this embodiment provides a sample processing system 300. This sample processing system 300 differs from the aforementioned sample processing system 100 in that the sample processing system 300 does not include a first mixing module. Instead, the sample processing system 300 utilizes a second mixing module 5a for sample mixing. The second mixing module 5a includes two opposing second adsorption devices 51a. When a sample carrier (e.g., magnetic beads) for capturing a biological sample is loaded into the reaction vessel 10, the sample carrier needs to be mixed with the biological sample or reagents to ensure that the biological sample is fully bound or captured on the sample carrier, or that the carrier carrying the biological sample is in full contact with the reagents.

[0144] The second mixing module 5a includes two opposing second adsorption devices 51a, forming a receiving space 55a between the two second adsorption devices 51a. The reaction vessel 10 can be placed in this receiving space 55a. The two second adsorption devices 51a are configured to alternately switch on and off to generate an attractive force, which is used to move a sample carrier containing a captured biological sample toward the corresponding second adsorption device 51a. This alternating attractive force generated by the two second adsorption devices 51a allows the sample carrier to reciprocate between the two second adsorption devices 51a, thereby achieving operations such as mixing or cleaning. In some embodiments, the second adsorption device 51a has a second contoured outer wall 52a corresponding to the outer wall of the reaction vessel 10. The second contoured outer wall 52a is configured to conform to or be as close to the outer wall of the reaction vessel 10 as possible.

[0145] In some embodiments, the second adsorption device 51a includes a second adsorption seat 53a and a second adsorption body 54a provided on the second adsorption seat 53a. Specifically, the structure of the second adsorption device 51a in this embodiment is basically the same as the structure of the first adsorption device 61 in the aforementioned embodiment. For details, please refer to the aforementioned embodiment 1, and no further details will be given here.

[0146] In some embodiments, the second adsorption device 51a may be a magnetic frame, and the second adsorption body 54a may be a magnet.

[0147] The specific mixing process is: place the reaction container 10 loaded with the mixed mixture into the accommodating space 55a between the two second adsorption devices 51a, alternately start the two second adsorption devices 51a, and the two second adsorption devices 51a alternately generate attraction. The sample carrier will be alternately adsorbed to the opposite sides of the reaction container 10, thereby realizing the sample carrier's counter-swimming in the reaction container 10 to achieve the purpose of mixing or cleaning.

[0148] In this embodiment, by setting up a second mixing module 5a and alternating power on and off of the two second adsorption devices 51a, automatic mixing of the mixture containing the sample carrier can be achieved, with high mixing efficiency, good mixing effect, simple operation, and the structure of the sample processing system 300 can be simplified.

[0149] Example 4

[0150] Referring to FIG. 28 , this embodiment provides a sample processing system 400. This sample processing system 400 differs from the aforementioned sample processing system 100 in that the first mixing module is not provided in the sample processing system 400. Instead, the pipetting device 21 in the sample processing system 400 is further configured to inject and / or aspirate a fluid, including a liquid or gas, into a mixture containing at least two samples to mix the mixture. Specifically, a pipette tip is loaded onto the pipette device 21, inserted into a reaction vessel, and fluid is introduced into and / or aspirated from the mixture. The mixture is then mixed by repeated injection and aspiration.

[0151] The sample processing system 400 of this embodiment can effectively mix a mixture containing at least two samples by multiple aspirations, with high mixing efficiency and good mixing effect. In addition, no separate mixing device is required, which helps to simplify the sample processing system 100 and reduce costs.

[0152] It is understood that one of the four mixing methods mentioned in Examples 1 to 4 can be selected, or any two, three, or four methods can be selected as needed to perform sample mixing operations. By adopting multiple mixing methods, the flexibility of process development is effectively improved. The corresponding mixing method can be selected according to different steps, which can not only meet the mixing requirements, but also avoid the impact of a single mixing method on the single-molecule sequencing library, especially reducing the risk of long fragment library interruption.

[0153] Example 5

[0154] Referring to FIG. 29 , this embodiment provides a sample processing system 500. This sample processing system 500 differs from the aforementioned sample processing system 100 in that it does not include a cover opening / closing module, i.e., it eliminates the fixed clamping device. Instead, it utilizes open reaction vessels as consumables, without sealing caps. The entire sample processing process utilizes an open-container method. Similarly, sample processing systems 200, 300, or 400 may also utilize open reaction vessels without a cover opening / closing module.

[0155] The sample processing system 500 of this embodiment adopts a fully open process and does not require a cover opening and closing process, which is conducive to simplifying the operation process, improving sample processing efficiency, and simplifying the structure of the sample processing system 500.

[0156] Example 6

[0157] Please refer to Figure 30. This embodiment provides a sample processing system 600. The difference between this sample processing system 600 and the aforementioned sample processing system 500 is that: no transfer device is provided in the sample processing system 600, that is, the whole process does not require the transfer of reaction vessels. At this time, an open reaction vessel is selected and no sealing cover is provided. Specifically, the sample in the reaction vessel can be sucked by the pipetting device 21 and transferred between the storage module 1, the incubation module 3, and the separation and purification module 6. At the same time, sample mixing is achieved by suction and injection. For specific suction and injection methods, please refer to the aforementioned embodiment 3. In this embodiment, it is necessary to place open reaction vessels in the incubation module 3 and the separation and purification module 6 in advance. If some sample processing processes require multiple incubations (such as the end repair process and the connector connection process in the preparation of the Chinese library in gene sequencing), the number of the incubation module 3 and the separation and purification module 6 needs to be increased according to actual conditions.

[0158] Example 7

[0159] Referring to FIG. 31 , this embodiment provides a sample processing system 700. This sample processing system 700 includes all the functional modules described in Examples 1 through 6 above, namely, the sample processing system 700 comprises a storage module 1, a transfer module 2, an incubation module 3, a control module 4, a first mixing module 5, a second mixing module 5a, a separation and purification module 6, and a lid-opening module 7. The transfer module 2 comprises a pipetting device 21 and a transfer device 22. The required reaction vessels can be selected later, either with sealed lids or open lids. The control module 4 is pre-configured with various sample processing logic programs. Engineers have access to this sample processing system 700, allowing them to flexibly select the desired logic program based on different application requirements. The transfer device 22, the first mixing module 5, the second mixing module 5a, and the lid-opening module 7 are optional modules; none or at least one of them can be selected to implement the sample processing procedures described in Examples 1 through 5. This sample processing system 600 is highly adaptable and suitable for a variety of application scenarios.

[0160] An embodiment of the present application also provides a biochemical reaction system 1000, which may include the aforementioned sample processing system 100 (200, 300, 400, 500, 600 or 700). The sample processing system 100 (200, 300, 400, 500, 600 or 700) may cooperate with other functional platforms to realize different biochemical reaction scenarios.

[0161] Please refer to FIG. 32 . The biochemical reaction system 1000 may be a gene sequencing system, such as a sequencer. The sample processing system 100 ( 200 , 300 , 400 , 500 , 600 or 700 ) may be used for sample processing during the gene sequencing process.

[0162] In other embodiments, the biochemical reaction system 1000 can also be a library construction instrument, and the aforementioned sample processing system 100 (200, 300, 400, 500, 600 or 700) can be used to construct a library in gene sequencing. After the library preparation is completed using the aforementioned sample processing system 100 (200, 300, 400, 500, 600 or 700), the library can be sequenced on the sequencer.

[0163] The aforementioned sample processing system 100 (200, 300, 400, 500, 600, or 700) can be used to construct libraries during single-molecule sequencing, automating the entire sample input and library output process without requiring human intervention. Multi-channel library construction can also be performed simultaneously, significantly reducing labor costs. The number of channels can also be increased as needed, thereby increasing library capacity. It is understood that the aforementioned sample processing system 100 (200, 300, 400, 500, 600, or 700) can also be used to process samples in other biochemical reaction processes.

[0164] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present application and are not intended to limit the present application. Although the present application has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present application may be modified or replaced by equivalents without departing from the spirit and scope of the technical solutions of the present application.

Claims

1. A sample processing system, characterized in that: include: a storage module, a transfer module, at least one incubation module and a control module, The storage module is configured to store samples required for biochemical reactions; The incubation module is configured to provide a preset temperature for a biochemical reaction; The transfer module is configured to transfer the sample; and The control module is configured to control the transfer module and the incubation module to work in coordination.

2. The sample processing system according to claim 1, wherein: The sample processing system further includes a first mixing module, wherein the first mixing module includes a mixing device configured to carry a reaction container loaded with the sample. The mixing device is further configured to provide a rotational force along a first direction and / or a second direction to drive the reaction container to rotate along the first direction and / or the second direction, wherein the first direction is opposite to the second direction.

3. The sample processing system according to claim 2, wherein: The mixing device comprises: a hybrid drive configured to provide a rotational force in the first direction and / or the second direction; and A rotating assembly is provided on the output shaft of the hybrid drive component. The rotating assembly has a placement slot for placing the reaction container. The rotating assembly is configured to drive the reaction container to rotate along the first direction and / or the second direction under the drive of the hybrid drive component.

4. The sample processing system according to claim 3, wherein: The hybrid drive is configured to provide a linear rotational force along the first direction and / or the second direction, and the rotating assembly is configured to convert the linear rotational force into an eccentric rotational force to drive the reaction container to perform eccentric rotational motion along the first direction and / or the second direction.

5. The sample processing system according to claim 2, wherein: The first mixing module further includes a blocking device configured to block the reaction container from escaping from the mixing device during the rotation process.

6. The sample processing system according to claim 5, wherein: The blocking device includes: a blocking driving member and a blocking arm provided on the blocking driving member. The blocking arm is configured to move to above the reaction container on the mixing device under the drive of the blocking drive member, so that the blocking arm is in a blocking state; or, the blocking arm is also configured to move away from above the reaction container on the mixing device under the drive of the blocking drive member, so that the blocking arm is in a non-blocking state.

7. The sample processing system according to claim 1, wherein: The sample processing system further includes a separation and purification module, which is configured to separate and purify the sample, wherein the sample contains a sample carrier for binding to a biological sample.

8. The sample processing system according to claim 7, wherein: The separation and purification module includes a first adsorption device, which is configured to generate an attractive force. The attractive force is used to move the sample carrier combined with the biological sample toward the first adsorption device to separate and purify the biological sample.

9. The sample processing system according to claim 8, wherein: The sample is loaded in a reaction container, and the first adsorption device has a first contoured outer wall corresponding to the outer wall of the reaction container, and the first contoured outer wall is configured to be in contact with or close to the outer wall of the reaction container.

10. The sample processing system according to claim 9, wherein: The first adsorption device includes a first adsorption seat and a first adsorption body detachably arranged on the first adsorption seat, the first adsorption body includes an adsorption surface, the adsorption surface constitutes part of the first contoured outer wall, and the adsorption surface is configured to fit the outer wall of the reaction container.

11. The sample processing system according to claim 10, wherein: The first adsorption device includes a bottom and a contoured portion located on the bottom, the contoured portion has an inclined surface, the inclined surface is recessed toward the inner side of the contoured portion to form at least one mounting groove, the first adsorption body is located in the mounting groove, and the adsorption surface and the inclined surface constitute the first contoured outer side wall.

12. The sample processing system according to claim 1, wherein: The sample processing system includes a second mixing module, which is configured to mix the sample, wherein the sample contains a sample carrier for binding to a biological sample, and the sample is loaded in a reaction container. The second mixing module includes two oppositely arranged second adsorption devices, and a accommodating space is formed between the two adsorption devices. The accommodating space is configured to accommodate the reaction container. The two second adsorption devices are configured to be alternately powered on and off to alternately generate an attractive force, and the attractive force is used to move the sample carrier bound to the biological sample toward the corresponding second adsorption device.

13. The sample processing system according to claim 12, wherein: The second adsorption device has a second contoured outer wall corresponding to the outer wall of the reaction container, and the second contoured outer wall is configured to be in contact with or close to the outer wall of the reaction container.

14. The sample processing system according to claim 1, wherein: The storage module includes a consumable carrier, which includes multiple functional areas. The multiple functional areas include a first type of area and a second type of area. The first type of area has multiple first through holes, and the second type of area has multiple second through holes. The hole depth of the first through hole is smaller than the hole depth of the second through hole. The first through hole and the second through hole are configured to place different consumables.

15. The sample processing system according to claim 14, wherein: The first type of areas include: a sample area, wherein the first through hole of the sample area is configured to place a reaction container loaded with a sample; a transfer area, wherein the first through hole in the transfer area is configured to temporarily store reaction containers loaded with samples or empty reaction containers; a processing area, wherein the first through hole of the processing area is configured to place a reaction container loaded with a mixed sample; a product zone, wherein the first through hole of the product zone is configured to place a reaction container loaded with a product; and The reagent area includes the first through hole configured to accommodate a reagent container loaded with a reagent.

16. The sample processing system according to claim 15, wherein: The sample area, the transfer area and the product area are all provided with identification marks.

17. The sample processing system according to claim 15, wherein: The processing area has an installation cavity, and the installation cavity is configured to accommodate a second mixing module or a separation and purification module.

18. The sample processing system according to claim 14, wherein: The second type of area includes a tip area. The second through-hole in the tip area is configured to accommodate a tip. The pipetting device in the transfer module is configured to cooperate with the tip to transfer the liquid sample. Assuming the length of the tip is H, the depth of the second through-hole is greater than or equal to 1 / 2H.

19. The sample processing system according to claim 14, wherein: The reaction container has a sealing cover, and the multiple functional areas further include a third type of area, which includes a sealing cover temporary storage area. The sealing cover temporary storage area has multiple grooves, and the grooves are configured to temporarily store the sealing cover removed from the reaction container.

20. The sample processing system according to claim 14, wherein: The plurality of functional areas further include a fourth type of area, wherein the fourth type of area includes a waste liquid area having a waste liquid tank configured to accommodate waste liquid.

21. The sample processing system according to claim 14, wherein: The consumable carrier further includes a marking area, which is used to locate the multiple areas, and / or The consumable carrier further includes an identification area, on which an identification code is provided.

22. The sample processing system according to claim 14, wherein: The consumable carrier is an integrated structure, or The consumable carrier includes a plurality of independent carrier units, and each of the carrier units has at least one functional area.

23. The sample processing system according to claim 14, wherein: The storage module further includes a carrier carrying device, and the consumable carrier is detachably mounted on the carrier carrying device.

24. The sample processing system according to claim 1, wherein: The storage module also includes a reaction container for loading the sample, the reaction container including a first cavity and a second cavity that are connected and communicated with each other, the inner diameter of the second cavity is smaller than the inner diameter of the first cavity, and the inner diameter of the second cavity decreases successively in a direction away from the first cavity.

25. The sample processing system of claim 1, wherein: The incubation module comprises: base; a heat dissipation device, disposed on the base; The heating device includes a temperature control structure provided on the heat dissipation device and a heating seat provided on the temperature control structure. The heating seat has at least one heating groove for accommodating a reaction container loaded with the sample. The temperature control structure is used to regulate the temperature of the heating groove so that the sample in the reaction container undergoes a biochemical reaction. The inner wall of the heating groove has a contoured structure corresponding to the outer wall of the reaction container.

26. The sample processing system according to claim 25, wherein: Along the depth direction of the heating groove, the heating groove includes a first groove and a second groove that are connected to each other, the inner diameter of the second groove is smaller than the inner diameter of the first groove, and the inner diameter of the second groove decreases successively in the direction away from the first groove.

27. The sample processing system according to claim 25, wherein: Along the depth direction of the heating groove, the heating groove includes a first groove, a second groove and a third groove that are connected in sequence. The inner diameters of the second groove and the third groove are both smaller than the inner diameter of the first groove. The inner diameter of the second groove decreases in the direction away from the first groove. The inner diameter of the third groove is equal to the inner diameter of the end of the second groove away from the first groove.

28. The sample processing system of claim 25, wherein: The heating seat includes a heating base and a plurality of heating slots located on a side of the heating base away from the temperature control structure. Each heating slot has a heating slot, and there is a gap between two adjacent heating slots so that the plurality of heating slots are independently arranged.

29. The sample processing system of claim 1, wherein: The sample processing system includes a plurality of the incubation modules, and the plurality of incubation modules are used to execute different temperature intervals.

30. The sample processing system of claim 1, wherein: The incubation module is further configured to temporarily store the product after the biochemical reaction.

31. The sample processing system of claim 1, wherein: The transfer module includes a pipetting device configured to transfer the sample.

32. The sample processing system of claim 31, wherein: The pipetting device is further configured to inject and / or aspirate fluid into the sample to mix the sample, wherein the fluid includes liquid or gas.

33. The sample processing system of claim 31, wherein: The transfer module further includes a transfer device, the sample is loaded in a reaction container, and the transfer device is configured to transfer the reaction container.

34. The sample processing system of claim 33, wherein: The reaction container has a sealing cover, and the sample processing system also includes a switch cover module, which includes a fixed clamping device and the transfer device. The fixed clamping device is configured to fix the reaction container, and the transfer device is also configured to cooperate with the fixed clamping device to open or close the sealing cover on the reaction container.

35. The sample processing system of claim 33, wherein: The transfer module includes a robotic arm and a rotating jaw assembly provided on the robotic arm. The robotic arm is configured to drive the rotating jaw assembly to move in multiple directions. The rotating jaw assembly can rotate in multiple directions to grasp or release the reaction container.

36. The sample processing system of claim 35, wherein: The pipetting device is integrated on the robotic arm.

37. The sample processing system of claim 1, wherein: The sample processing system further includes a detection and quantification module, which is configured to detect and quantify a product of a biochemical reaction in the sample.

38. A sample processing system, characterized in that: include: A storage module, a transfer module, at least one incubation module, a separation and purification module, a first mixing module, a second mixing module, a switch cover module and a control module, The storage module is configured to store samples required for biochemical reactions; The incubation module is configured to provide a preset temperature for a biochemical reaction; The transfer module includes a pipetting device and a transfer device, wherein the pipetting device is configured to transfer the sample by aspirating, and the transfer device is configured to transfer a reaction container loaded with the sample; and The control module is configured to control the transfer module, the incubation module, the separation and purification module, the first mixing module, the second mixing module and the cover opening and closing module to work in coordination. The control module is further configured to provide an operator with a choice to execute a sample processing program that does not include the transfer device, the first mixing module, the second mixing module, and the cover-opening module, or to execute a sample processing program that includes at least one of the transfer device, the first mixing module, the second mixing module, and the cover-opening module.

39. A biochemical reaction system, characterized in that: Comprising a sample processing system as claimed in any one of claims 1 to 38.

40. The biochemical reaction system according to claim 39, wherein: The biochemical reaction system is a library construction instrument or a sequencer.

Images