Sample processing device

Abstract

The utility model relates to the technical field of biological sample detection, in particular to a sample treatment device, and aims to solve the problems that an existing sample treatment device is complex in operation and low in working efficiency. To this end, the sample processing apparatus of the present application comprises: a frame body; a manipulator mechanism; a first container and a second container, the first container is used for accommodating a sample solution, the second container is used for accommodating an extraction solution, magnetic beads are arranged in the first container, and the magnetic beads are used for enriching a target extract in the sample solution; the manipulator mechanism can clamp the first magnetic assembly and insert the first magnetic assembly into the first container so as to adsorb the magnetic beads in the first container and transfer the magnetic beads into the second container; and the second magnetic component is close to the second container and is used for adsorbing the magnetic beads in the second container so as to separate the target extract from the magnetic beads. The sample processing device provided by the utility model can improve the sample processing efficiency.

Description

Technical Field

[0001] This application relates to the technical field of biological sample detection, and specifically provides a sample processing device. Background Art

[0002] With the progress of nanotechnology and biomaterials science, specific magnetic beads, as a new type of biological separation material, are widely used in the enrichment of low-abundance proteins. This enrichment method has the advantages of simple operation, high enrichment efficiency, strong specificity, etc., and thus has received extensive attention.

[0003] In some related technologies, the magnetic bead enrichment method mainly includes two types: pipetting type and magnetic rod type. Although these two methods can improve the enrichment efficiency of low-abundance proteins, since existing biological sample processing devices are usually designed for only one of these methods, they cannot simultaneously process large-volume samples and extract and concentrate them into small-volume samples. For example, since the concentration of low-abundance proteins in the sample is low, in order to obtain a sample with a higher concentration, it is necessary to enrich and concentrate a large-volume sample into a small volume, thereby improving the detection sensitivity. However, as mentioned above, existing biological sample processing devices usually only support a single enrichment method. In this way, when processing large-volume samples, they have low efficiency and complex operations, and cannot effectively enrich and concentrate biological samples such as low-abundance proteins.

[0004] Therefore, a new technical solution is needed in this field to solve the above problems. Utility Model Content

[0005] This application aims to solve the above technical problems, that is, to solve the problems of complex operation, low working efficiency of existing sample processing devices, and inability to handle large-volume samples and extract and concentrate small-volume samples at the same time.

[0006] This application provides a sample processing device, including:

[0007] A frame body;

[0008] A manipulator mechanism, which is arranged on the frame body;

[0009] A first container and a second container, the first container is used to hold a sample solution, the second container is used to hold an extraction solution, magnetic beads are arranged in the first container, and the magnetic beads are used to enrich target extracts in the sample solution;

[0010] A first magnetic force assembly, which is arranged on the frame body, and the manipulator mechanism can clamp the first magnetic force assembly and insert the first magnetic force assembly into the first container to adsorb the magnetic beads in the first container and transfer the magnetic beads to the second container;

[0011] A second magnetic component, which is arranged on the frame body and is close to the second container, is used for adsorbing the magnetic beads in the second container to separate the target extract from the magnetic beads.

[0012] Optionally, the first magnetic component includes:

[0013] A magnetic rod holder, which is used for connecting with the manipulator mechanism, and a plurality of magnetic rods are arranged on the magnetic rod holder;

[0014] A magnetic rod sleeve holder, which is used for connecting with the manipulator mechanism, and magnetic rod sleeves corresponding to the magnetic rods are arranged on the magnetic rod sleeve holder. The manipulator mechanism can clamp the magnetic rod sleeve and insert or remove the magnetic rod sleeve into or out of the first container, and the manipulator mechanism can clamp the magnetic rod and insert or remove the magnetic rod into or out of the magnetic rod sleeve.

[0015] Optionally, grooves are arranged on both the magnetic rod holder and the magnetic rod sleeve holder, and a protrusion is arranged on the manipulator mechanism, and the protrusion can be clamped in the groove.

[0016] Optionally, the second magnetic component includes:

[0017] A magnetic seat, which is arranged on the frame body, and the second container is arranged on the magnetic seat;

[0018] A magnetic member, which is arranged on the magnetic seat and is close to the second container, and the magnetic member is used for adsorbing the magnetic beads in the second container.

[0019] Optionally, the sample processing device further includes:

[0020] A first liquid suction member, which is arranged on the manipulator mechanism, and the first liquid suction member is used for sucking the sample solution, and the manipulator mechanism can clamp the first liquid suction member and insert the first liquid suction member into the first container.

[0021] Optionally, the sample processing device further includes:

[0022] A second liquid suction member, which is arranged on the manipulator mechanism, and the second liquid suction member is used for sucking the extraction solution in the second container to separate the magnetic beads from the extraction solution.

[0023] Optionally, the sample processing device further includes:

[0024] A heating and oscillation module, which is arranged on the frame body, and the heating and oscillation module is used for heating and oscillating the sample solution.

[0025] Optionally, the sample processing device further includes:

[0026] The first guide rail is arranged on the frame body;

[0027] The second guide rail is arranged on the first guide rail, and the manipulator mechanism is slidably connected to the second guide rail;

[0028] Wherein, the extending direction of the first guide rail and the extending direction of the second guide rail are arranged at an angle.

[0029] Optionally, the sample processing device further includes:

[0030] A centrifugal separation mechanism is arranged on the frame body, and the centrifugal separation mechanism is used for centrifuging the sample solution.

[0031] Optionally, the sample processing device further includes:

[0032] A controller, and the manipulator mechanism, the heating and oscillation module and the centrifugal separation mechanism are all electrically connected to the controller.

[0033] In the case of adopting the above technical solution, the sample processing device provided by the present application drives the first magnetic component to move through the manipulator mechanism, thereby realizing the transfer and washing process of the magnetic beads, and improving the efficiency and accuracy during sample processing. Subsequently, through the second magnetic component, the efficient separation of the magnetic bead-protein complex is realized, so as to accurately separate the required target extract.

[0034] Through the cooperation of the first magnetic component and the second magnetic component, the above sample processing device can not only reduce the complexity of the operation, but also process a large number of samples simultaneously, thereby improving the working efficiency of the sample processing device. Description of the Drawings

[0035] The following describes the preferred embodiments of the present application with reference to the drawings. In the drawings:

[0036] Figure 1 is a schematic structural diagram of a sample processing device according to an embodiment of the present application;

[0037] Figure 2 is a schematic structural diagram of a magnetic rod sleeve assembly according to an embodiment of the present application;

[0038] Figure 3 is a schematic structural diagram of a magnetic rod assembly according to an embodiment of the present application;

[0039] Figure 4 is a schematic structural diagram of a manipulator mechanism according to an embodiment of the present application;

[0040] Figure 5 is a schematic structural diagram of a second magnetic component according to an embodiment of the present application.

[0041] List of reference signs:

[0042] 1 - Frame body, 11 - Bottom plate, 10 - Controller, 20 - Manipulator mechanism, 201 - Jaw, 2011 - Protrusion, 21 - First guide rail, 22 - Second guide rail, 24 - First driving motor, 61 - Magnetic bar assembly, 611 - Magnetic bar holder, 612 - Magnetic bar, 613 - First seat body, 62 - Magnetic bar sleeve assembly, 621 - Magnetic bar sleeve holder, 622 - Magnetic bar sleeve, 623 - Second seat body, 63 - Groove, 701 - Half - skirted 96 - well PCR plate, 711 - Second driving motor, 72 - Magnetic plate, 712 - Clamping device, 713 - Magnetic seat, 714 - Adapter, 81 - First liquid suction part, 82 - Second liquid suction part, 91 - Heating and oscillation module, 92 - Centrifugal separation mechanism. Specific embodiments

[0043] The following describes the preferred embodiments of the present application with reference to the accompanying drawings. Those skilled in the art should understand that these embodiments are only used to explain the technical principles of the present application and are not used to limit the protection scope of the present application. Those skilled in the art can make adjustments according to needs to adapt to specific application scenarios.

[0044] It should be noted that in the description of the present application, terms indicating directions or positional relationships such as "upper", "lower", "left", "right", "inner", "outer", etc. are based on the directions or positional relationships shown in the drawings. This is only for convenience of description and does not indicate or imply that the relevant devices or components must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation of the present application. In addition, ordinal numbers such as "first" and "second" are only used for descriptive purposes and cannot be understood as indicating or implying relative importance.

[0045] In addition, it should also be noted that in the description of the present application, unless otherwise clearly specified and limited, the terms "installation" and "connection" should be understood in a broad sense. For example, it can be a fixed connection, a detachable connection or an integral connection; it can be a mechanical connection or an electrical connection; it can be directly connected or indirectly connected through an intermediate medium. For those skilled in the art, the specific meanings of the above terms in the present application can be understood according to specific circumstances.

[0046] Please refer to Figures 1-5 , a sample processing device according to an embodiment of the present application. The sample processing device includes a frame body 1. The frame body 1 is the main support structure of the sample processing device, providing a accommodation space and a mounting space for each processing module required for sample processing, enabling them to cooperate orderly according to the experimental process, execute processing processes such as biological sample extraction and purification, and provide a basis for improving the efficiency of biological sample processing.

[0047] The processing module is arranged on the bottom plate 11 of the frame body 1, and a two-dimensional moving platform is arranged in the area of the frame body 1 near the top. The execution component manipulator mechanism 20 in the sample processing device is arranged on this two-dimensional moving platform. The manipulator mechanism 20 is mainly used to achieve precise sample processing operations, such as the transfer and distribution of sample solutions, etc., and at the same time supports the automatic control of complex experimental processes.

[0048] Specifically, as Figure 1 shown, guide rails are arranged on the frame body 1 along two different directions of the device. The first guide rail 21 is arranged in the first direction, the second guide rail 22 is arranged in the second direction, and the second guide rail 22 is also slidably connected to the first guide rail 21.

[0049] Furthermore, the manipulator mechanism 20 is installed on the second guide rail 22 and can slide along the second direction. Since the second guide rail 22 is slidably connected to the first guide rail 21, the mechanical structure can also move along the first direction, enabling it to achieve omnidirectional movement capabilities in a two-dimensional plane.

[0050] In this way, during the sample processing, the manipulator mechanism 20 can quickly move and position between different processing modules, thereby ensuring the coherence and efficiency of the experimental process, and improving the operation accuracy and overall efficiency of the sample processing device.

[0051] In a specific embodiment, as Figure 1 shown, the first direction and the second direction are perpendicular to each other.

[0052] In this embodiment, low-abundance proteins are taken as an example of the target extract for illustration.

[0053] The processing steps for extracting low-abundance proteins generally involve a washing step (removing sample impurities) and an elution step (separating the extract from the magnetic beads), and the first container is not only used to hold the sample solution but also holds the washing solution in the washing step, while the second container is used for the elution operation in the elution step.

[0054] Furthermore, the volume of the first container is larger than that of the second container.

[0055] Specifically, since the collection amount of the sample solution (such as blood) is usually large and a large amount of washing solution is also required during the washing process, a container with a larger volume is selected as the first container to hold these solutions; while the elution process requires concentrating the sample content to improve the detection sensitivity, and the cost of the elution solution is generally relatively high, so a container with a smaller volume is selected as the second container. In this way, not only can the sample be effectively concentrated, but also the usage amount of the elution solution can be reduced, saving costs.

[0056] Such a design not only meets the demand for a large volume during the washing process, improving the processing efficiency, but also takes into account the requirements of concentrating the sample and saving costs during the elution process.

[0057] The complete process of sample processing is as follows:

[0058] In the first step of the sample processing, it is necessary to preprocess the sample solution to remove impurities therein.

[0059] In one embodiment, the sample processing device includes a centrifugal separation mechanism 92 disposed on the bottom plate 11 of the frame body 1. The preprocessing of the sample solution is carried out by the centrifugal separation mechanism 92. The centrifugal separation mechanism 92 can remove impurities in the sample solution by means of high-speed rotation and centrifugation.

[0060] Specifically in this embodiment, in plasma or serum samples, the content of high-abundance proteins and cellular components is rich, and these components may interfere with the detection signals of low-abundance proteins. However, by using the centrifugal separation mechanism 92, impurities such as red blood cells and platelets in plasma or serum can be effectively removed, thereby obtaining a clear sample solution.

[0061] The second step in the sample processing is to lyse and enrich the sample solution.

[0062] In one embodiment, as Figure 2 shown, a first liquid suction member 81 is provided on the manipulator mechanism 20, and the first liquid suction member 81 is used to suck the preprocessed sample solution.

[0063] Specifically, the first liquid suction member 81 sucks the clarified part of the sample solution under the drive of the manipulator mechanism 20 and transfers these solutions to the first container.

[0064] Furthermore, in the first container, magnetic beads are pre-loaded. These magnetic beads are used to enrich target extracts, such as low-abundance proteins. In addition, a lysis solution is also pre-added to the first container, and its function is to promote the release of low-abundance proteins from the complex sample matrix, providing high-quality samples for subsequent analysis and experimental operations. The method of pre-loading magnetic beads and lysis solution into the reaction container can improve the efficiency of sample processing.

[0065] In a specific embodiment, the first container is preferably a 96-well deep plate. The single-well volume of the 96-well deep plate is generally 1.5 - 3.0 ml, and preferably 2.0 ml or 2.2 ml in this embodiment. The first liquid suction member 81 is preferably an eight-channel pipette. This not only improves the throughput and efficiency of sample processing, but also enhances the automation of the experiment, making it more convenient and efficient for operators to operate.

[0066] Specifically, first, a 96-well deep well plate is a high-density container that can accommodate multiple samples simultaneously within a limited experimental space, which can greatly improve the throughput and efficiency of sample processing.

[0067] Secondly, compared with traditional single-channel pipettes, an eight-channel pipette can aspirate or dispense multiple samples simultaneously, reducing the operation time and further enhancing the processing efficiency.

[0068] In addition, the combined use of an eight-channel pipette and a 96-well deep well plate also improves the automation level of the experiment. Through programming control, precise liquid transfer and dispensing can be achieved, reducing human operation errors and improving the reliability and repeatability of experimental operations.

[0069] In one embodiment, as Figure 1 shown, a heating and oscillation module 91 is also provided on the frame body 1. The lysis step is completed in the heating and oscillation module 91.

[0070] Specifically, after aspirating the sample solution into the first container, the first container (such as a 96-well deep well plate) is transferred to the heating and oscillation module 91 by the manipulator mechanism 20.

[0071] In this module, the sample solution mixed with the lysis buffer is oscillated to accelerate the mixing of the two solutions. At the same time, the sample mixture solution is heated to increase the release rate of low-abundance proteins. During the oscillating mixing process, the antibodies on the surface of the magnetic beads specifically bind to the low-abundance proteins in the sample, forming a magnetic bead-protein complex. This magnetic separation technology can efficiently enrich and separate the target extract from the sample solution.

[0072] The third step in the sample processing is washing. Washing refers to the process of cleaning the magnetic beads enriched with the target extract to remove non-specific binding substances and impurities.

[0073] In one embodiment, the sample processing device includes a first magnetic force assembly, and in this embodiment, the first magnetic force assembly is used to wash the magnetic beads.

[0074] Specifically, the first magnetic force assembly is provided on the frame body 1, and the manipulator mechanism 20 can clamp the first magnetic force assembly and insert the first magnetic force assembly into the first container to adsorb the magnetic beads in the first container and transfer the magnetic beads to a washing container pre-filled with washing liquid, so as to achieve the functions of adsorbing, transferring, and cleaning the magnetic beads.

[0075] Specifically, as Figures 1-4As shown, the first magnetic component includes a magnetic rod component 61 and a magnetic rod sleeve component 62. The magnetic rod component 61 includes a magnetic rod 612 and a magnetic rod holder 611 for supporting the magnetic rod 612. The magnetic rod sleeve component 62 includes a magnetic rod sleeve 622 and a magnetic rod sleeve holder 621 for supporting the magnetic rod sleeve 622.

[0076] In one embodiment, grooves 63 are provided on both the magnetic rod holder 611 and the magnetic rod sleeve holder 621, and protrusions 2011 are provided on the jaws 201 of the manipulator mechanism 20. The protrusions 2011 can be snapped into the grooves 63 to ensure that they can be firmly embedded and snapped together, making the process of gripping and transferring the magnetic rod holder 611 and the magnetic rod sleeve holder 621 more stable.

[0077] Further, when the magnetic rod component 61 and the magnetic rod sleeve component 62 are not in operation, they are respectively seated on a first base 613 and a second base 623. The first base 613 and the second base 623 are both provided on the bottom plate 11 and are arranged adjacent to each other, so that the manipulator mechanism can easily grip and move these components during operation.

[0078] This compact layout not only optimizes the space utilization of the device, but also helps to improve the stability and accuracy of the operation of the manipulator mechanism 20, ensuring that they can accurately align with the target container in each operation step, thus realizing an efficient sample processing and washing process.

[0079] Further, the magnetic rods 612 are arranged on the magnetic rod holder 611 in an array form, and the structure of the magnetic rod sleeve 622 corresponds to that of the magnetic rods 612 and is also arranged on the magnetic rod sleeve holder 621 in an array nature. The material of the magnetic rods 612 usually selects rare earth magnetic materials to provide strong magnetic force. The function of the magnetic rod sleeve 622 is to protect the magnetic rods 612 and ensure that the magnetic rods 612 can be accurately inserted into or removed from the holes in the container to adsorb and transfer magnetic beads.

[0080] In a specific embodiment, the selection of the magnetic rods 612 includes 8 or 96, which are respectively suitable for 8 - row magnetic rod sleeves 622 and 96 - well magnetic rod sleeves 622. These components work together to enable the sample processing device to process multiple samples simultaneously, improving the operation efficiency.

[0081] Further, the jaws 201 can first insert the magnetic rod sleeve 622 into the first container, and then insert the magnetic rods 612 into the magnetic rod sleeve 622, so that the magnetic rods 612 can adsorb the magnetic beads in the sample solution. Subsequently, the jaws 201 can take out the magnetic rod sleeve 622 and the magnetic rods 612 (together with the adsorbed magnetic beads) and transfer them to a washing container pre - filled with washing liquid. During the washing process, the washing liquid can remove the non - specific adsorption substances on the magnetic beads.

[0082] Meanwhile, the gripper 201 can stir the washing liquid by driving the magnetic rod sleeve 622 to move up and down, so as to promote the washing of the magnetic beads.

[0083] Specifically, the process of transferring the magnetic beads from the first container to the washing container is as follows: The gripper 201 of the manipulator mechanism 20 first grabs the magnetic rod sleeve holder 621 and inserts it into the first container; subsequently, the gripper 201 grabs the magnetic rod holder 611 and inserts it into the magnetic rod sleeve 622. Under the strong magnetic force of the magnetic rod 612, the magnetic beads are adsorbed onto the magnetic rod sleeve 622; then, the gripper 201 grabs the magnetic rod sleeve holder 621 and the magnetic rod holder 611 simultaneously and inserts them together into the washing container pre-filled with washing liquid.

[0084] Then, the magnetic rod 612 is removed, and the magnetic rod sleeve 622 is used to stir the washing liquid. The specific process is as follows: The gripper 201 transfers the magnetic rod holder 611 to the first base 613, separating the magnetic rod 612 and the magnetic rod sleeve 622; subsequently, the gripper 201 grabs the magnetic rod sleeve holder 621 again and moves it in the up and down direction under the drive of the first drive motor 24 to stir the sample mixed solution, ensuring that the magnetic beads are thoroughly washed.

[0085] This process ensures the efficiency and accuracy of the magnetic beads during adsorption, transfer, and washing. Through the precise operation of the gripper 201, the automation and high-throughput processing capabilities of the sample processing device are realized, providing high-quality samples for subsequent experiments or analyses.

[0086] Furthermore, as described above, the structure of the gripper 201 moving the magnetic rod 612 and the magnetic rod sleeve 622 enables the operator to wash the magnetic beads multiple times according to experimental requirements, or, according to actual needs, different volumes of washing solutions can be used to wash the magnetic beads at different experimental stages. For example, during the first wash, since the magnetic beads may have adsorbed more impurities or unwanted substances, a larger amount of washing solution can be used to effectively remove these substances. In subsequent washes, if most of the impurities have been removed, a smaller volume of washing solution can be used to avoid the loss of target extracts due to overwashing.

[0087] In a specific embodiment, the washing container is preferably a 96-well deep well plate to accommodate a large number of samples. The 96-well deep well plate structure can also match with 96 magnetic rod sleeves 622 to ensure that each magnetic rod sleeve 622 can be accurately inserted into its respective well position, thereby effectively stirring and cleaning the samples during the washing process.

[0088] The fourth step of the sample processing process is elution. Elution refers to the process of removing the target extract (such as low-abundance proteins) from the surface of the magnetic beads.

[0089] In one embodiment, the sample processing device further includes a second magnetic assembly disposed on the frame body 1. The second magnetic assembly is close to the second container. Wherein, an elution solution is pre-loaded in the second container. Bringing the second magnetic assembly close to the second container helps to adsorb the magnetic beads in the second container to separate the target extract from the magnetic beads.

[0090] In one embodiment, the second container is preferably a 96-well PCR (i.e., Polymerase Chain Reaction) plate. Wherein, the volume of a single well of the PCR plate is selected to be 0.1 - 0.2 ml, which is conducive to concentrating the sample and reducing the amount of elution solution used to reduce costs.

[0091] Further, as Figure 1 and 5 shown, the second magnetic assembly includes a magnetic base 713 and a magnetic member disposed on the magnetic base 713. The magnetic member is disposed close to the second container to adsorb the magnetic beads in the second container.

[0092] The magnetic base 713 includes a magnetic plate 72 for fixing the magnetic member. Wherein, there are multiple magnetic members, and preferably spherical magnets or hemispherical magnets.

[0093] Specifically, using a 96-well PCR plate in combination with spherical magnets or hemispherical magnets to adsorb magnetic beads is conducive to aggregating the magnetic beads dispersed in the 96-well PCR plate into clusters, concentrating the magnetic beads in a smaller area. In this way, a smaller amount of elution solution can cover the magnetic beads. Therefore, using the adsorption method of spherical magnets or hemispherical magnets can achieve elution with a smaller volume of elution solution. The protein molecules eluted from the magnetic beads are released in a smaller space, which is equivalent to concentrating the sample. This concentration can increase the concentration of the protein, thereby improving the sensitivity and accuracy of detection.

[0094] Further, a clamping device 712 is also disposed on the magnetic base 713 for fixing the adapter 714 of the semi-skirted 96-well PCR plate 701. The adapter 714 of the PCR plate is to ensure that the PCR plate can be stably fixed on the magnetic base 713 during operation. The PCR plate adapter can stabilize the 96-well PCR plate on the magnetic base 713 for subsequent sample processing.

[0095] Further, a second driving motor 711 is also disposed on the magnetic base 713. The second driving motor 711 is fixed on the magnetic base 713 and is connected to the magnetic plate 72 through a transmission system. The second driving motor 711 drives the magnetic plate 72 to move the spherical magnet up and down in the elution solution, thereby effectively promoting the dissociation of the target extract (such as low-abundance protein) from the surface of the magnetic beads and dissolving it into the elution solution.

[0096] It should be understood that since the content of the target extract (such as low-abundance proteins) is generally small, and the cost of the elution solution is also high, in this example, a small-range eight-channel pipette is used as the second liquid suction member 82 to suck the extraction solution to obtain the target extract, and the extraction solution is the elution solution in which the target extract (such as low-abundance proteins) is dissolved.

[0097] Due to the high cost of the elution solution, by using the second liquid suction member 82, the target substances in the solution can be utilized to the maximum extent, thereby improving the economy and efficiency of the experiment. This method is particularly suitable for experimental processes that require a large amount of elution solution, such as the extraction of low-abundance molecules in biological samples.

[0098] In a specific embodiment, in summary, the sample processing device provided in this embodiment controls the movement of the first magnetic assembly through the robotic mechanism 20, thereby realizing the transfer and washing processes of magnetic beads, and improving the efficiency and accuracy during sample processing. Subsequently, by utilizing the magnetic field attraction property of the second magnetic assembly, the separation of the magnetic bead-protein complex is achieved, thereby accurately separating the required target extract.

[0099] This sample processing device not only improves the efficiency of the sample processing process, but also reduces the operation cost and time consumption, realizes the efficient processing of large-volume samples, enriches and concentrates the large-volume samples into small volumes, increases the protein concentration in the samples, thereby improving the detection sensitivity, and making the processing of biological samples more efficient and reliable.

[0100] The fifth step of the sample processing process is spotting on the target plate. Spotting on the target plate is the process of using the second liquid suction member 82 to spot the extraction solution onto the pre-focused target plate. The main purpose of this step is to position the sample on the target plate, usually in preparation for subsequent mass spectrometry detection.

[0101] Furthermore, the sample processing device further includes a target plate heating and drying device, which is used to heat the target plate after spotting to accelerate the crystallization of the matrix for subsequent mass spectrometry analysis.

[0102] In one embodiment, the sample processing device further includes a controller 10, which is responsible for the operation of the entire device to ensure that each module works according to a preset program.

[0103] For example, the controller can monitor including the robotic mechanism 20, the heating and oscillation module, and the target plate heating and drying device, etc. The operator sets and optimizes various parameters according to the experimental requirements, such as the heating temperature, the suction speed and position of the liquid suction member, and the liquid dispensing amount of the pipette. The precise setting of these parameters is crucial for the efficiency of sample processing and the reliability of the results.

[0104] Through the automation function of the controller 10, the operator can reduce human errors and operation inconsistencies, ensuring the repeatability and accuracy of the experiment. For example, during the spotting process on the target plate, the controller 10 can precisely control the liquid dispensing volume and position of each spot, avoiding cross-contamination and waste of samples.

[0105] In a specific embodiment, taking the extraction of IGF-1 (Insulin-like growth factor 1, known concentration in serum is 2 ng / mL), that is, insulin-like growth factor 1 as an example for illustration.

[0106] The first step is to preprocess the sample: A 5000 μL blood sample is preprocessed using the centrifugal separation mechanism 92.

[0107] The second step is to lyse and enrich the supernatant: Use the first liquid suction member 81 to aspirate 500 μL of the preprocessed supernatant and transfer it to the first container. The first container is selected as a 3000 μL 96-well deep well plate. Among them, the deep well plate is pre-loaded with 100 μL of magnetic beads conjugated with antibodies, 500 μL of PBS solution (i.e., phosphate buffer solution) containing 0.6% Tween-20 (i.e., polysorbate-20), and 750 μL of IGF-1 internal standard working solution; then, the 96-well deep well plate is transferred to the heating and oscillation module 91 by the manipulator mechanism 20 and heated and oscillated for about 5 minutes. Then, it is left to stand at room temperature for 10 minutes to allow the antibodies on the surface of the magnetic beads to fully bind to IGF-1 in the serum, forming a magnetic bead-protein complex.

[0108] The third step is to wash the magnetic beads enriched with IGF-1 to remove non-specific binding substances and impurities.

[0109] First, wash the magnetic beads with a large volume of washing solution. Specifically: Use the gripper 201 to first insert the magnetic rod sleeve 622 into the 96-well deep well plate, and then insert the magnetic rod 612 into the magnetic rod sleeve 622 to adsorb the magnetic beads. Subsequently, the gripper 201 removes the magnetic rod sleeve 622 and the magnetic rod 612 (along with the adsorbed magnetic beads) and transfers them to the first washing container (i.e., pre-loaded with a large volume of washing solution). Among them, the first washing container is also a 96-well deep well plate, and the first washing container is pre-loaded with 1000 μL of PBS washing solution containing 0.1% Tween-20. Then, the gripper 20 removes the magnetic rod 612 and drives the magnetic rod sleeve 622 to move up and down for about 1 minute to stir the washing solution and promote the washing of the magnetic beads.

[0110] Then, the magnetic beads are washed a second time using a small volume of wash solution. Specifically, the above actions are repeated, i.e., the gripper 201 is used again to first insert the magnetic rod sleeve 622 into the wash container, then insert the magnetic rod 612 into the magnetic rod sleeve 622 to adsorb the magnetic beads, and transfer the magnetic beads to a second wash container (i.e., pre-filled with a small volume of wash solution). Here, the second wash container is a 96-well deep plate, and the second wash container is pre-filled with 200 μL of deionized water wash solution. Then, similar to the above stirring action, the gripper 201 is used to drive the magnetic rod sleeve 622 to move up and down to stir the wash solution for about 1 minute.

[0111] Among them, both the first wash container and the second wash container can be pre-set on the bottom plate 11 to simplify the wash process and facilitate the transfer of magnetic beads between the two by the first magnetic assembly.

[0112] In this embodiment, the example of washing the magnetic beads twice is used for illustration. Of course, multiple groups of wash containers can also be set as needed, and the first magnetic assembly is used to achieve the transfer of magnetic beads between each wash container and to stir the wash solution to promote the washing of magnetic beads.

[0113] Fourth step, elution, that is, the process of separating the magnetic beads and IGF-1 and extracting IGF-1.

[0114] Specifically, after the washing is completed, 200 μL of deionized water sample is transferred into the second container, and magnetic separation is carried out using the second magnetic assembly. Then, the deionized water wash solution in the second container is removed using the first liquid suction member 81; 2 μL of extraction solution (the extraction solution can also be understood as elution solution or matrix solution) is added into the second container using the second liquid suction member 82 to elute the IGF-1 protein from the magnetic beads.

[0115] Fifth step: spotting on the target plate: The second magnetic assembly is brought close to the second container to use the spherical magnet in the second magnetic assembly to adsorb the magnetic beads in the second container, separate IGF-1 from the magnetic beads, and transfer 2 μL of the extraction solution to the target plate using the second liquid suction member 82.

[0116] Sixth step, mass spectrometry detection. In this step, the target plate is heated using a heating and drying device. After all the samples on the target plate are crystallized, data is collected using MALDI TOF MS (Matrix-Assisted Laser Desorption / Ionization Time-of-Flight Mass Spectrometry), that is, matrix-assisted laser desorption tandem time-of-flight mass spectrometer.

[0117] As can be seen from the above description, in the washing and elution steps, it is possible to gradually concentrate a large volume of sample solution into a small volume of sample solution, and this process is achieved through the coordinated cooperation of the first magnetic assembly and the second magnetic assembly.

[0118] The sample processing device provided by the embodiments of the present application has significant advantages.

[0119] First, 500 μL of serum (with a known IGF-1 concentration of 2 ng / mL) can be concentrated and enriched to obtain 2 μL of the sample to be tested. The protein concentration in the sample is increased by 250 times, and the final concentration is 500 ng / mL. This process not only increases the concentration of the sample but also ensures that it is higher than the minimum detection limit (2 ng / mL) of MALDI TOF MS, making the sample processing more efficient and feasible. Second, the concentration of 500 ng / mL also meets the minimum requirements for protein detection by spectrophotometry, which means that the applicability of the device in different detection methods has been improved.

[0120] Therefore, the sample processing device can not only improve the automation degree of sample processing of the MALDI TOF MS mass spectrometer, providing convenience for related experiments, but also has a high degree of compatibility and can be widely applied to a variety of detection devices.

[0121] So far, the technical solutions of the present application have been described in conjunction with the preferred embodiments shown in the drawings. However, it is easy for those skilled in the art to understand that the protection scope of the present application is obviously not limited to these specific embodiments. Without departing from the principle of the present application, those skilled in the art can make equivalent changes or substitutions to the relevant technical features, and the technical solutions after these changes or substitutions will fall within the protection scope of the present application.

Claims

1. A sample processing device, characterized in that: include: Framework body; A manipulator mechanism, which is arranged on the frame body; A first container and a second container, wherein the first container is used to contain a sample solution, and the second container is used to contain an extraction solution, the volume of the first container is greater than the volume of the second container, and magnetic beads are arranged in the first container, and the magnetic beads are used to enrich the target extract in the sample solution; A first magnetic component is disposed on the frame body, and the manipulator mechanism is capable of clamping the first magnetic component and inserting the first magnetic component into the first container to absorb the magnetic beads in the first container and transfer the magnetic beads to the second container; A second magnetic component is disposed on the frame body and is close to the second container, and is used for adsorbing the magnetic beads in the second container to separate the target extract from the magnetic beads.

2. The sample processing device according to claim 1, characterized in that: The first magnetic component comprises: A magnetic rod rack, which is used to connect with the manipulator mechanism, and a plurality of magnetic rods are arranged on the magnetic rod rack; A magnetic rod sleeve rack is used to be connected to the manipulator mechanism, and the magnetic rod sleeve rack is provided with a magnetic rod sleeve corresponding to the magnetic rod. The manipulator mechanism can clamp the magnetic rod sleeve and insert or remove the magnetic rod sleeve from the first container, and the manipulator mechanism can clamp the magnetic rod and insert or remove the magnetic rod from the magnetic rod sleeve.

3. The sample processing device according to claim 2, characterized in that: The magnetic rod frame and the magnetic rod sleeve frame are both provided with grooves, and the manipulator mechanism is provided with protrusions, which can be snapped into the grooves.

4. The sample processing device according to claim 1, characterized in that: The second magnetic component comprises: A magnetic base, which is arranged on the frame body, and the second container is arranged on the magnetic base; A magnetic member is disposed on the magnetic base and close to the second container, and is used to absorb the magnetic beads in the second container.

5. The sample processing device according to claim 1, characterized in that: The sample processing device also includes: The first liquid absorbing member is arranged on the manipulator mechanism, and is used for absorbing the sample solution. The manipulator mechanism can clamp the first liquid absorbing member and insert the first liquid absorbing member into the first container.

6. The sample processing device according to claim 1, characterized in that: The sample processing device also includes: The second liquid absorbing member is arranged on the manipulator mechanism, and is used for absorbing the extraction solution in the second container to separate the magnetic beads from the extraction solution.

7. The sample processing device according to claim 1, characterized in that: The sample processing device also includes: A first guide rail, which is arranged on the frame body; A second guide rail, which is arranged on the first guide rail, and the manipulator mechanism is slidably connected to the second guide rail; Wherein, an extension direction of the first guide rail and an extension direction of the second guide rail are arranged at an angle.

8. The sample processing device according to any one of claims 1 to 7, characterized in that: The sample processing device also includes: The heating and oscillating module is arranged on the frame body, and is used for heating and oscillating the sample solution.

9. The sample processing device according to claim 8, characterized in that: The sample processing device also includes: The centrifugal separation mechanism is arranged on the frame body and is used for centrifuging the sample solution.

10. The sample processing device according to claim 9, characterized in that: The sample processing device also includes: A controller, wherein the manipulator mechanism, the heating oscillation module and the centrifugal separation mechanism are all electrically connected to the controller.

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