Biological sample preparation and detection integrated system

Abstract

The utility model provides a biological sample preparation and detection integrated system which comprises a carrying platform, a connector, a reactor capable of carrying biological reaction and a detector capable of carrying biological detection, a vertical working mechanism, a liquid transfer device for transferring liquid and a magnetic operation device for adsorbing magnetic beads. Compared with the prior art, the device has the following beneficial effects that by arranging the carrying table, the detector, the vertical working mechanism and the sealed reaction bin, one instrument can be used for sample pretreatment and subsequent automatic detection, the working process of the device can be set, and an open system is wide in applicability and high in practicability. The kit can be used for nucleic acid purification, nucleic acid amplification detection, methylation detection, protein purification and the like, is wide in application range and high in compatibility, and effectively solves the problems that an experimenter needs to insert a plurality of instruments and each instrument needs to be preheated and prepared for an experiment due to the singleness of sample pretreatment and detection equipment. And the efficiency of experimental detection is greatly improved.

Description

Technical Field

[0001] This utility model belongs to the field of biological sample preparation and detection technology, and specifically relates to a comprehensive system for biological sample preparation and detection. Background Technology

[0002] Biological samples, including blood, body fluids, saliva, and tissues, are rich in the biological information of organisms. Typically, through the preparation and processing of biological samples, small molecules and fragments such as nucleic acids and proteins that can be further analyzed are extracted. Then, the required biological information is obtained through molecular diagnostics or immunoassay.

[0003] Traditionally, such analyses often require multiple pieces of equipment, such as incubation equipment, pipetting equipment, and detection equipment. Due to the diversity of bioanalyses, detection equipment might be a PCR instrument for molecular diagnostics or a chemiluminescence analyzer for immunoassay. Because sample pretreatment and detection equipment are often limited, biological laboratories are typically cluttered and large, requiring lab technicians to navigate between numerous instruments, each requiring its own preheating and preparation – a time-consuming and labor-intensive process. Therefore, we aim to design a novel integrated system for biological sample preparation and detection to address this problem. Utility Model Content

[0004] In view of the shortcomings of the existing technology, the purpose of this utility model is to provide a comprehensive system for biological sample preparation and detection, and to solve the problems mentioned in the background technology.

[0005] This utility model is achieved through the following technical solution: a comprehensive system for biological sample preparation and detection, including: a stage and a connector, which can carry the reactor required for biological reaction and the detector required for biological detection;

[0006] A vertical working mechanism, including a pipetting device for liquid transfer and a magnetic manipulation device for magnetic bead adsorption;

[0007] The stage is located below the vertical working mechanism. The stage and the vertical working mechanism can move relative to each other in the horizontal and vertical directions. The pipetting device and magnetic manipulation device of the vertical working mechanism can pass through the reactor and biological detector on the stage to transfer liquid or magnetically adsorb it.

[0008] In a preferred embodiment, the platform is mounted on a horizontal motion guide rail in the horizontal direction, and the platform can move horizontally along the horizontal motion guide rail via a drive device, and the movement of the platform forms a relative movement in the horizontal direction with the vertical working mechanism.

[0009] Alternatively, the vertical working mechanism may be mounted on a horizontal motion guide rail in the horizontal direction. The vertical working mechanism may move horizontally along the horizontal motion guide rail via a drive device, and the movement of the vertical working mechanism may form a relative movement with the platform in the horizontal direction.

[0010] As a preferred embodiment, the reactor required for the biological reaction includes at least a storage device and may also include a biological reaction temperature control device. The storage device can hold at least two or more liquid components and can hold at least the pipette tip and magnetic sleeve required for the biological reaction.

[0011] The memory can be linear or array-type. The bioreactor temperature control device can control the temperature of all or individual locations of the memory to provide the temperature required for the bioreactor. In actual use, the bioreactor temperature control device can be a product model currently on the market, and the specific selection can be determined according to the specifications of the memory.

[0012] In a preferred embodiment, the vertical working mechanism is mounted on a vertical motion guide rail in the vertical direction, and the vertical working mechanism can move in the vertical direction along the vertical motion guide rail by a driving device.

[0013] The vertical working mechanism is equipped with a piston and a piston drive device. The connector head is provided with a vertical through hole. The piston is placed in the through hole of the connector head. A magnetic rod is provided at the bottom of the piston. The front end of the connector head bottom is connected with the magnetic sleeve to perform magnetic transfer operation. It can also be used with the pipette head to perform pipetting operation.

[0014] The vertical working mechanism is also equipped with a vertical motion transmission rod for power transmission.

[0015] In a preferred embodiment, the biological detector can move along a detector motion guide rail that is parallel to the direction of the reaction tube arrangement. The biological detector includes at least a detection device and may also include a filter and an excitation light source.

[0016] The reaction tube carried by the biodetector can also be pre-loaded with solid paraffin. The solid paraffin is in a liquid state after heating to seal the reaction system, and in a solid state after cooling to seal the reaction tube. In actual use, the biodetector is also equipped with a biodetection temperature control device located on the lower side of the reaction tube. The biodetection temperature control device can provide the temperature environment required for real-time detection of the biological reaction. Existing market products can be used for the biodetection temperature control device, and the specific selection can be determined according to the specifications of the detector.

[0017] A pressure cap is also installed on the top of the biodetector.

[0018] In a preferred embodiment, the system further includes a circuit control module and a negative pressure suction module;

[0019] The stage moves horizontally to the innermost part of the instrument and fits tightly against the frame at the rear of the instrument. In actual use, the stage moves horizontally to the rear of the instrument and forms a sealed reaction chamber by sealing the frame at the rear of the instrument with the sealing gasket located on the upper side of the biological detector. The circuit control module of the system controls the fan in the negative pressure suction module located at the rear of the sealed reaction chamber to work and draw air, so that a negative pressure environment is formed in the area where the sealed biological detector is located, avoiding contamination during the biological reaction process.

[0020] After adopting the above technical solution, the beneficial effects of this utility model are as follows: by setting up a stage, detector, vertical working mechanism and sealed reaction chamber, a single instrument can perform sample pretreatment and subsequent automated detection. The equipment workflow can be set, and the open system has wide applicability. It can perform nucleic acid purification, nucleic acid amplification detection, methylation detection, protein purification, etc. It has a wide range of uses and strong compatibility. It effectively solves the problem that due to the single nature of sample pretreatment and detection equipment, the experimenter needs to switch between many instruments and each instrument needs to be preheated and prepared for the experiment. It greatly improves the efficiency of experimental detection.

[0021] By setting up a memory, along with a detector and a vertical working mechanism, only reagent kits and consumables need to be prepared before the experiment, simplifying the experimental process, making it easier to operate, and greatly reducing the difficulty of biological detection.

[0022] The vertical working mechanism, with its vertical motion module one and vertical motion module two, is compatible with both liquid transfer and magnetic transfer operations. This makes the entire device simple in structure, compact in size, and highly tolerant of errors. Attached Figure Description

[0023] To more clearly illustrate the technical solutions in the embodiments of this utility model or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this utility model. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0024] Figure 1 This is a schematic diagram of the overall structure of a comprehensive biological sample preparation and detection system according to the present invention.

[0025] Figure 2 This is a schematic diagram showing the connection between the stage and the detector in a comprehensive biological sample preparation and detection system according to this utility model.

[0026] Figure 3This is a schematic diagram of the internal structure of the stage and detector of the integrated system for biological sample preparation and detection according to this utility model.

[0027] Figure 4 This is a schematic diagram of the cross-sectional structure of the vertical working mechanism of the integrated biological sample preparation and detection system of this utility model.

[0028] Figure 5 This is a schematic diagram of the magnetic sleeve structure installed on the vertical working mechanism of the integrated biological sample preparation and detection system of this utility model.

[0029] Figure 6 This is a schematic diagram of the vertical working mechanism of the integrated biological sample preparation and detection system of this utility model, showing the installation of a pipette head.

[0030] Figure 7 This is a schematic diagram of the pipette tip aspiration (A) of a comprehensive biological sample preparation and detection system according to this utility model.

[0031] Figure 8 This is a schematic diagram of the pipette tip separation (B) of a comprehensive biological sample preparation and detection system according to this utility model.

[0032] Figure 9 This is a schematic diagram of the magnetic sleeve installation (A) of the integrated system for biological sample preparation and detection according to this utility model.

[0033] Figure 10 This is a schematic diagram of the magnetic sleeve attracting magnets (B) of a comprehensive biological sample preparation and detection system according to this utility model.

[0034] Figure 11 This is a schematic diagram of the magnetic sleeve separation (C) of a comprehensive biological sample preparation and detection system according to this utility model.

[0035] Figure 12 This is a schematic diagram of the platform of the integrated biological sample preparation and detection system of this utility model moving to the lower side of the vertical working mechanism.

[0036] Figure 13 This is a schematic diagram of the sealed reaction chamber suction air path structure of a comprehensive biological sample preparation and detection system according to this utility model.

[0037] In the diagram, 1-stage, 11-memory, 111-bioreactor temperature control device, 112-magnetic sleeve, 113-pipette, 114-magnetic bead, 12-biodetector, 121-reaction tube, 122-cap, 123-detection device, 124-biodetector temperature control device, 125-detector motion guide rail, 126-sealing gasket, 13-horizontal motion guide rail, 2-vertical working mechanism, 3-sealed reaction chamber, 31-vertical motion guide rail, 32-vertical motion transmission rod, 33-connector, 34-piston through hole, 35-front end piece, 36-piston, 37-magnetic rod. Detailed Implementation

[0038] The technical solutions of the present utility model will be clearly and completely described below with reference to the accompanying drawings of the embodiments. Obviously, the described embodiments are only some embodiments of the present utility model, and not all embodiments. Based on the embodiments of the present utility model, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the protection scope of the present utility model.

[0039] Please see Figures 1 to 13 This utility model provides a technical solution: a comprehensive system for biological sample preparation and detection, including: a stage 1 and a connector 33, which can carry the reactor required for biological reaction and the detector required for biological detection;

[0040] The vertical working mechanism 2 includes a pipetting device for liquid transfer and a magnetic actuation device for adsorption of the magnetic beads 114.

[0041] The stage 1 is located below the vertical working mechanism 2. The stage 1 and the vertical working mechanism 2 can move relative to each other in the horizontal and vertical directions. The pipetting device and magnetic manipulation device of the vertical working mechanism 2 can pass through the reactor and biological detector 12 on the stage 1 to transfer liquid or magnetically adsorb it.

[0042] Please see Figures 1 to 3 The platform 1 is set on the horizontal motion guide rail 13 in the horizontal direction, and the platform 1 can move horizontally along the horizontal motion guide rail 13 by the drive device. The movement of the platform 1 forms a relative movement in the horizontal direction with the vertical working mechanism 2.

[0043] Alternatively, the vertical working mechanism 2 can be set on the horizontal motion guide rail 13 in the horizontal direction. The vertical working mechanism 2 can move in the horizontal direction along the horizontal motion guide rail 13 through the drive device. The movement of the vertical working mechanism 2 forms a relative movement with the platform 1 in the horizontal direction.

[0044] The reactor required for the biological reaction includes at least a storage device 11 and may also include a biological reaction temperature control device 111. The storage device 11 can hold at least two or more liquid components and can hold at least a pipette head 113 and a magnetic sleeve 112 required for the biological reaction.

[0045] The memory 11 can be linear or array-type. The biological reaction temperature control device 111 can control the temperature of all or individual locations of the memory 11 to provide the temperature required for the biological reaction. In actual use, the biological reaction temperature control device 111 can be a product model that is already on the market. The specific selection can be determined according to the specifications of the memory 11.

[0046] As the first embodiment of this utility model, since the stage 1 and the vertical working mechanism 2 can move relative to each other in the horizontal direction, in actual operation, the stage 1 can move horizontally along the horizontal motion guide rail 13, while the vertical working mechanism 2 does not move horizontally. The stage 1 carries a storage device 11 and a biological detector 12 (a PCR reaction detector) for nucleic acid extraction. When the stage 1 moves, it will synchronously drive the storage device 11 and the biological detector 12. Some positions at the bottom of the storage device 11 have biological reaction temperature control devices 111, which can heat the corresponding positions of the storage device 11 to provide the temperature for nucleic acid extraction reaction and elution. The storage device 11 is an array type, which can hold the reaction solution and magnetic beads required for nucleic acid extraction. The reaction tube 121 contains liquid, washing solution, and elution solution, and can also carry a pipette tip 113 for pipetting operations and a magnetic sleeve 112 for magnetic transfer operations. The reaction tube 121 is a standard PCR eight-tube set. A solid paraffin ring can be built into the PCR tube. The side of the reaction tube 121 has a detection device 123, which can move linearly along the detector motion guide rail to detect all positions of the reaction tube 121. The detection device 123 includes an excitation light source, a filter, and a detection device, which can perform real-time fluorescence excitation detection of the reactants in the reaction tube 121. The bottom of the reaction tube 121 has a biological detection temperature control device 124, which is a Peltier device that can rapidly raise and lower the temperature to provide the PCR temperature environment required by the reaction tube 121.

[0047] By setting up the memory 11, in conjunction with the biological detector 12 and the vertical working mechanism 2, only the reagent kit and consumables need to be prepared before the experiment, which simplifies the experimental process, makes it easier to operate, and greatly reduces the difficulty of biological detection.

[0048] The vertical working mechanism 2, with its vertical motion module 1 and vertical motion module 2, is compatible with both liquid transfer and magnetic transfer operations. This makes the entire device simple in structure, compact in size, and highly tolerant of errors.

[0049] Please see Figures 1 to 13The vertical working mechanism 2 is set on the vertical motion guide rail 31 in the vertical direction. The vertical working mechanism 2 can move in the vertical direction along the vertical motion guide rail 31 by the drive device.

[0050] The vertical working mechanism 2 is equipped with a piston 36 and a piston drive device. The connector 33 is equipped with a vertical through hole. The piston 36 is installed in the through hole of the connector 33. The bottom of the piston 36 is equipped with a magnetic rod 37. The front end part 35 at the bottom of the connector 33 is connected with the magnetic sleeve 112 to perform magnetic transfer operation, and can also be used with the pipette head 113 to perform pipetting operation.

[0051] The vertical working mechanism 2 is also equipped with a vertical motion transmission rod 32 for power transmission.

[0052] The biological detector 12 can move along the detector motion guide rail 125, which is parallel to the arrangement direction of the reaction tube 121. The biological detector 12 includes at least a detection device 123, and may also include a filter and an excitation light source.

[0053] The reaction tube 121 carried by the biodetector 12 can also be pre-loaded with solid paraffin. When heated, the solid paraffin is in a liquid state to seal the reaction system, and when cooled, it is in a solid state to seal the reaction tube 121. In actual use, the biodetector 12 is also equipped with a biodetection temperature control device 124 and is placed under the reaction tube 121. The biodetection temperature control device 124 can provide the temperature environment required for real-time detection of the biological reaction. The biodetection temperature control device 124 can be any existing product model on the market, and the specific selection can be determined according to the specifications of the detector.

[0054] A pressure cap 122 is also installed on the upper side of the biodetector 12.

[0055] The system also includes a circuit control module and a negative pressure suction module;

[0056] The stage 1 moves horizontally to the innermost part of the instrument and fits tightly against the frame at the rear of the instrument. In actual use, the stage 1 moves horizontally to the rear of the instrument and is sealed against the frame at the rear of the instrument through the sealing gasket 126 located on the upper side of the biodetector 12 to form a sealed reaction chamber 3. The circuit control module in the system controls the fan located at the rear of the sealed reaction chamber 3 in the negative pressure suction module to work and draw air, so that a negative pressure environment is formed in the area where the sealed biodetector 12 is located, avoiding contamination during the biological reaction process.

[0057] As a second embodiment of this utility model, based on the first embodiment described above, the vertical working mechanism 2 has two sets of vertical motion modules. One is a vertical motion module one (vertical motion module one is preferably a cylinder structure, capable of vertical lifting and lowering, or other vertical motion structures that meet the requirements can be selected) used to control the vertical movement of the connector 33. The other is a vertical motion module two used to control the vertical movement of the piston 36. Specifically, the connector 33 moves vertically along the vertical motion guide rail 31. In conjunction with the horizontally moving platform 1, the connector 33 can be aligned with any position on the platform 1. The connector 33 has a piston 36 inside, and a magnetic rod 37 is connected to the bottom of the piston 36. The piston 36 can move along the vertical motion guide rail 31. The piston 36 moves vertically through the hole 34. The front end part 35 at the bottom of the piston head can be tightly engaged with the pipette head 113 or the magnetic sleeve 112. When the front end part 35 is engaged with the pipette head 113, the piston 36 moves and can compress or expand the air to transfer the liquid. When the front end part 35 is engaged with the magnetic sleeve 112, the magnetic rod 37 moves to the bottom of the magnetic sleeve 112. At this time, the magnetic rod 37 and the magnetic sleeve 112 descend together into the liquid of the magnetic bead 114 in the memory 11, so that the magnetic bead 114 can be attracted to the outer wall of the magnetic sleeve 112. When the piston 36 descends further, the magnetic rod 37 at its front end can transmit pressure to the pipette head 113 or the magnetic sleeve 112 connected to the front end part 35, thereby pushing out the pipette head 113 or the magnetic sleeve 112.

[0058] Before the PCR reaction detection process begins, the stage 1 moves inward along the horizontal motion guide rail 13 until the sealing gasket 126 on the biodetector 12 on the stage 1 is tightly combined with the frame at the rear of the instrument to form a sealed reaction chamber 3. During the PCR reaction detection process, the fan located at the rear of the instrument begins to draw air outward. At this time, the airflow enters through the ventilation holes at the bottom of the instrument and then enters the sealed chamber through the ventilation holes on one side of the sealing gasket 126, and is exhausted from the rear of the instrument. Since the airflow path is unidirectional, even if aerosols are generated during the PCR reaction, they will not enter the instrument and will be exhausted to the outside of the instrument by the fan at the rear of the instrument. (The above embodiment is illustrated using nucleic acid extraction and PCR amplification detection as an example. That is, the application of the bioreactor in this embodiment is nucleic acid extraction, the application of the biodetector 12 is qPCR, and the detection principle is fluorescence detection. That is, the detection device 123 in this embodiment is a fluorescence detection device 123.)

[0059] This utility model also relates to the equipment's workflow:

[0060] 1. The stage 1 is removed from the container. The user places the storage device 11 on the stage 1 and places the reaction tube 121 (PCR reaction tube) containing the PCR reaction reagent on the biological detector 12.

[0061] 2. Remove and install the magnetic sleeve 112 from the connector 33;

[0062] 3. The stage 1 and the vertical working mechanism 2 move in coordination to remove the magnetic bead 114 from the liquid and place it into the nucleation reaction site of the memory 11.

[0063] 4. During the mixing process within the nuclear extraction reaction site, the vertical working mechanism 2 moves the magnetic sleeve 112 up and down through the connector 33 to mix the system, while the biological reaction temperature control device 111 controls the temperature inside the storage device 11.

[0064] 5. Connector 33 will adsorb and transfer the magnetic beads 114, which have been cleaved, bound, and coated with nucleic acid in the reaction position of memory 11, to the cleaning position for cleaning operation;

[0065] 6. The cleaned magnetic beads 114 are transferred to the elution position by the connector 33 for elution operation;

[0066] 7. Connector 33 retracts magnetic sleeve 112 into magnetic sleeve 112 position in memory 11, and then connector 33 installs pipette 113 at pipette 113 position;

[0067] 8. The pipette 113 connected to the connector 33 removes the nucleic acid extraction solution from the elution position of the storage 11 and adds it to the reaction tube 121 (PCR reaction tube);

[0068] 9. The biological detection temperature control device 124 of the biological detector 12 (PCR reaction detector) is working to control the temperature in the reaction tube 121, and the detection device 123 performs fluorescence detection.

[0069] 10. After the experiment, the biological detection temperature control device 124 of the biological detector 12 (PCR reaction detector) is cooled down, and the paraffin in the reaction tube 121 (PCR reaction tube) becomes solid below the melting point, and the reaction tube 121 (PCR reaction tube) is sealed.

[0070] The above description is only a preferred embodiment of the present utility model and is not intended to limit the present utility model. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present utility model should be included within the protection scope of the present utility model.

Claims

1. A comprehensive system for biological sample preparation and detection, characterized in that, include: The stage (1) and connector (33) can support the reactor required for biological reaction and the detector required for biological detection; The vertical working mechanism (2) includes a pipetting device for liquid transfer and a magnetic manipulation device for adsorption of magnetic beads (114); The stage (1) is located below the vertical working mechanism (2). The stage (1) and the vertical working mechanism (2) can move relative to each other in the horizontal and vertical directions. The pipetting device and magnetic manipulation device of the vertical working mechanism (2) can pass through the reactor and biological detector (12) on the stage (1) to transfer liquid or magnetically adsorb it.

2. The integrated system for biological sample preparation and detection as described in claim 1, characterized in that: The platform (1) is set on the horizontal motion guide rail (13) in the horizontal direction, and the platform (1) can move horizontally along the horizontal motion guide rail (13) by a drive device. The movement of the platform (1) forms a relative movement in the horizontal direction with the vertical working mechanism (2). Alternatively, the vertical working mechanism (2) may be set on a horizontal motion guide rail (13) in the horizontal direction. The vertical working mechanism (2) may move in the horizontal direction along the horizontal motion guide rail (13) by a drive device. The movement of the vertical working mechanism (2) and the platform (1) form a relative movement in the horizontal direction.

3. The integrated system for biological sample preparation and detection as described in claim 1, characterized in that: The reactor required for the biological reaction includes at least a storage device (11) and may also include a biological reaction temperature control device (111). The storage device (11) can hold at least two or more liquid components and can hold at least a pipette tip (113) and a magnetic sleeve (112) required for the biological reaction. The memory (11) can be linear or array-type, and the biological reaction temperature control device (111) can control the temperature of all or some locations of the memory (11) to provide the temperature required for the biological reaction.

4. The integrated system for biological sample preparation and detection as described in claim 3, characterized in that: The vertical working mechanism (2) is set on the vertical motion guide rail (31) in the vertical direction. The vertical working mechanism (2) can move in the vertical direction along the vertical motion guide rail (31) by a driving device. The vertical working mechanism (2) is provided with a piston (36) and a piston driving device. The connector (33) is provided with a vertical through hole. The piston (36) is located in the through hole of the connector (33). A magnetic rod (37) is provided at the bottom of the piston (36). The front end part (35) at the bottom of the connector (33) is connected with the magnetic sleeve (112) to perform magnetic transfer operation. The front end part (35) is connected with the pipette head (113) to perform pipetting operation.

5. The integrated system for biological sample preparation and detection as described in claim 1, characterized in that: The biological detector (12) can move along a detector motion guide rail (125) whose setting direction is parallel to the arrangement direction of the reaction tube (121). The biological detector (12) includes at least a detection device (123) and may also include a filter and an excitation light source. The reaction tube (121) carried by the biodetector (12) can also be pre-loaded with solid paraffin. The solid paraffin is in a liquid state after heating to seal the reaction system, and in a solid state after cooling to seal the reaction tube (121).

6. The integrated system for biological sample preparation and detection as described in claim 1, characterized in that: The system also includes a circuit control module and a negative pressure suction module. The stage (1) moves horizontally to the innermost side of the instrument and fits tightly against the frame at the tail of the instrument.

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