Sample extraction device and nucleic acid detection integrated device equipped with the same
The specimen extraction device with a compact layout addresses the large footprint issue of integrated nucleic acid detection devices by optimizing the arrangement of specimen loading, reaction, and gripping areas, enabling efficient nucleic acid extraction and replication with reduced space requirements.
Patent Information
- Application Number
- JP2023211189
- Authority / Receiving Office
- JP · JP
- Patent Type
- Patents
- Current Assignee / Owner
- Priority Date
- 2023-01-19
- Filing Date
- 2023-12-14
- Publication Date
- 2025-08-12
- Estimated Expiration
- 2043-12-14
AI Technical Summary
The existing integrated nucleic acid detection devices have a large footprint due to the need for multiple modules to work together for DNA extraction and replication.
A specimen extraction device with a compact layout, featuring a specimen loading area, sample reaction area, and gripping area arranged around the sample reaction area, along with transfer members for specimen and reaction vessels, allowing for efficient nucleic acid extraction and replication with reduced space requirements.
The compact layout reduces the overall footprint of the integrated nucleic acid detection device while maintaining efficient nucleic acid extraction and replication processes.
Smart Images

Figure 0007721622000001 
Figure 0007721622000002 
Figure 0007721622000003
Abstract
Description
[Technical Field]
[0001] The present invention relates to the technical field of biological detection, and more particularly to a specimen extraction device and an integrated nucleic acid detection device equipped with the same. [Background technology]
[0002] Currently, nucleic acid detection is widely used in fields such as clinical diagnosis, agricultural monitoring, and food safety. The most commonly used nucleic acid detection method is PCR detection. The general principle of PCR detection is that, under the catalytic action of DNA polymerase, parent strand DNA is used as a template and specific primers are used as elongation initiation points to replicate complementary child strand DNA in vitro.
[0003] In the prior art, when extracting and replicating parental DNA, the integrated nucleic acid detection device requires multiple modules to work together to extract the parental DNA from the sample using an extraction reagent, and then transfer the parental DNA to an amplification reagent for replication.
[0004] However, when multiple modules work together, the integrated nucleic acid detection device requires an excessively large footprint. Summary of the Invention [Problem to be solved by the invention]
[0005] The present invention provides a specimen extraction device and an integrated nucleic acid detection device equipped with the same, in order to solve the problem of the related art that the footprint of an integrated nucleic acid detection device is too large. [Means for solving the problem]
[0006] According to one aspect of the present invention, a specimen extraction device is provided which includes a specimen loading area provided with a specimen loading section for storing and processing specimen tubes, a sample reaction area provided with a sample reaction section for extracting nucleic acid from the specimen, a sample addition area provided with a sample addition section for transferring the specimen from the specimen loading section to a first reaction vessel and adding the nucleic acid extracted in the sample reaction section to a second reaction vessel, and a gripping area provided with a gripping section for moving the first reaction vessel from the sample addition section to the sample reaction section after the specimen has been added and for moving the first reaction vessel from the sample reaction section to the sample addition section, wherein the specimen loading area, sample addition area and gripping area are all arranged around the outside of the sample reaction area, and the gripping area is located on the same side of the specimen loading area, sample reaction area and sample addition area.
[0007] Furthermore, the sample extraction device further includes a sample tube transfer member, a reaction vessel transfer member, and an extraction mechanism transfer member, wherein the sample tube transfer member is movably arranged between the sample loading area and the sample addition area to move the sample tube in the sample loading area to the sample addition area, the reaction vessel transfer member is movably arranged between the sample addition area and the grabbing area to move the first reaction vessel and the second reaction vessel in the sample addition area between the sample addition area and the grabbing area, and the extraction mechanism transfer member is movably arranged between the sample reaction area and the grabbing area to move the first reaction vessel between the sample reaction area and the grabbing area.
[0008] Furthermore, the specimen tube transfer member is movably arranged along a first horizontal direction between the specimen loading area and the sample addition area, the reaction vessel transfer member is movably arranged along a second horizontal direction between the sample addition area and the grabbing area, and the extraction mechanism transfer member is movably arranged along the second horizontal direction between the sample reaction area and the grabbing area, the first horizontal direction and the second horizontal direction being perpendicular to each other.
[0009] Furthermore, the reaction vessel transfer member includes a first reaction vessel transfer member and a second reaction vessel transfer member that are arranged in parallel, and the first reaction vessel transfer member and the second reaction vessel transfer member are both provided between the sample addition area and the gripping area so as to be movable along a second horizontal direction, and the sample addition section includes a liquid transfer needle that is provided so as to be movable above the first reaction vessel transfer member and the second reaction vessel transfer member, and the first reaction vessel transfer section has a sample addition position located in the sample addition area, and when the first reaction vessel transfer member is located at the sample addition position, The delivery needle can move above the first reaction vessel transfer member to inject the sample into the first reaction vessel, and the second reaction vessel transfer member is located in the sample addition area and has a nucleic acid addition position that is flush with the first reaction vessel transfer member, and when the first reaction vessel transfer member is located at the sample addition position and the second reaction vessel transfer member is located at the nucleic acid addition position, the liquid transfer needle can move above the first reaction vessel transfer member to aspirate the extracted nucleic acid and move above the second reaction vessel transfer member to transfer the extracted nucleic acid to the second reaction vessel.
[0010] Furthermore, the specimen tube transfer member has a first working position located in the sample addition area, and when the specimen tube transfer member is located in the first working position, the liquid transfer needle can move above the specimen tube transfer member to aspirate the specimen.
[0011] Further, the sample loading section includes a sample tube gripper and a sample bottle for storing the sample tube, the sample tube gripper is movably arranged above the sample bottle and the sample tube transfer member, the sample tube transfer member further has a second working position located in the sample loading area, and when the sample tube transfer member is located in the second working position, the sample tube gripper can move the sample tube from the sample bottle to the sample tube transfer member, the gripping section includes a reaction vessel gripper arranged to be movable in a first horizontal direction and a first vertical direction, the extraction mechanism transfer member has a receiving position located in the gripping area and an extraction position located in the sample reaction area, the reaction vessel transfer member has a first transfer position located in the gripping area, and when the reaction vessel transfer member is located in the first transfer position and the extraction mechanism transfer member is located in the receiving position, the reaction vessel gripper can grip the first reaction vessel and move the first reaction vessel between the reaction vessel transfer member and the extraction mechanism transfer member.
[0012] Furthermore, the sample application section further includes a consumable storage bottle for placing the liquid transfer head thereon, and the liquid transfer needle can move above the consumable storage bottle to load the liquid transfer head.
[0013] Furthermore, the gripping area is further provided with a film sealing mechanism for sealing the second reaction vessel, and the reaction vessel transfer member further has a second transfer position located in the gripping area, and when the reaction vessel transfer member is located at the second transfer position, the reaction vessel gripper can move above the reaction vessel transfer member to grip the second reaction vessel after nucleic acid loading, and move above the film sealing mechanism to release the second reaction vessel into the film sealing mechanism.
[0014] Further, the film sealing mechanism includes a heat press member and a film sealing mechanism transfer member, and the film sealing mechanism transfer member is arranged below the heat press member so as to be movable along a second horizontal direction, and the film sealing mechanism transfer member has a lid body placing position for placing the lid body and a second reaction vessel placing position for placing the second reaction vessel, and the reaction vessel gripper can release the second reaction vessel to the second reaction vessel placing position, and the reaction vessel gripper has a gripping position located above the film sealing mechanism transfer member, and when the reaction vessel gripper is located at the gripping position, the film sealing mechanism transfer member has a separation position where the lid body placing position moves below the reaction vessel gripper and the reaction vessel gripper grabs the lid body, a release position where the second reaction vessel placing position moves below the reaction vessel gripper and the reaction vessel gripper releases the lid body to the second reaction vessel, and a sealing position where the second reaction vessel placing position moves below the heat press member.
[0015] Furthermore, the gripping area is further provided with a waste liquid station located below the reaction vessel gripper, the waste liquid station including a waste liquid frame, a tray, and a waste liquid collection member, the waste liquid collection member being movably mounted on the waste liquid frame along the vertical direction and the second horizontal direction, when the reaction vessel transfer member is located at the first transfer position, the reaction vessel gripper can move above the first reaction vessel transfer member to grab the first reaction vessel and move above the tray to release the first reaction vessel onto the tray, and the waste liquid collection member can move above the tray to collect the magnetic rod cover and waste liquid.
[0016] Furthermore, the waste liquid station further includes a support plate, a push rod, and a collection box, the collection box being located below the waste liquid frame, the tray being vertically movably mounted on the waste liquid frame, the push rod being movably mounted on the support plate along a second horizontal direction, the support plate having an evacuation opening for retracting the tray, the tray being able to move below the support plate to place the first reaction vessel on the support plate, and the push rod being able to push the first reaction vessel to collect the first reaction vessel in the collection box.
[0017] According to another aspect of the present invention, there is provided an integrated nucleic acid detection device including a reagent preparation device for preparing extraction reagents and amplification reagents, an amplification device for performing analyte detection measurements on the measurement mixture to analyze the sample, and the sample extraction device provided above.
[0018] Furthermore, the reagent preparation device, the analyte extraction device and the amplification device are isolated from each other, the reagent preparation device and the amplification device are respectively located on either side of the specimen extraction device, a first passage is provided between the reagent preparation device and the specimen extraction device, and a second passage is provided between the specimen extraction device and the amplification device, both of the first passage and the second passage have a blocked state and a conductive state, and / or the device further includes a transfer mechanism provided between the reagent preparation device and the specimen extraction device, the transfer mechanism being capable of moving a first reaction vessel for preparing the extraction reagent and a second reaction vessel for preparing the amplification reagent to the specimen extraction device through the first passage, and the gripping part of the specimen extraction device being capable of moving the first reaction vessel to a first reaction vessel position of the specimen extraction device and moving the second reaction vessel to a second reaction vessel position of the specimen extraction device. [Effects of the Invention]
[0019] By applying the technical means of the present invention, a specimen extraction device includes a specimen loading area, a sample reaction area, a sample addition area, and a grasping area, wherein the specimen loading area is provided with a specimen loading section capable of loading and processing specimen tubes containing specimens, the sample addition area is provided with a sample addition section capable of transferring the specimen from the specimen loading section to a first reaction vessel, and the grasping area is provided with a grasping section capable of moving the first reaction vessel after specimen addition from the sample addition section to the sample reaction section of the sample reaction area, thereby replicating nucleic acids by extracting nucleic acids from the specimen using the sample reaction section, and further using the grasping section to move the first reaction vessel after nucleic acid extraction from the sample reaction section to the sample addition section, and adding the extracted nucleic acids to a second reaction vessel. The specimen loading area, sample addition area, and grasping area are all located outside the sample reaction area, and the grasping area is located on the same side of the specimen loading area, sample reaction area, and sample addition area. Therefore, the layout between the modules of the specimen extraction device becomes more compact, and the layout of the integrated nucleic acid detection device also becomes more compact, so that the footprint of the integrated nucleic acid detection device becomes smaller.
[0020] The drawings constituting a part of this application are intended to provide a further understanding of the present invention, and the illustrative embodiments of the present invention and the description thereof are intended to provide an understanding of the present invention and are not intended to unduly limit the present invention. [Brief explanation of the drawings]
[0021] [Figure 1] 1 shows a partition diagram of a specimen extraction device according to an embodiment of the present invention. [Figure 2] 1 is a diagram showing the structure of a specimen extraction device according to an embodiment of the present invention; [Figure 3] 1 is a diagram showing the structure of a sample reaction unit and an extraction mechanism transfer member of a specimen extraction device according to an embodiment of the present invention. FIG. [Figure 4] 3 is a diagram showing the structure of a film sealing mechanism of the specimen extraction device according to the embodiment of the present invention. FIG. [Figure 5]3A and 3B are diagrams showing the structures of a cover opening member and a specimen tube transferring member of a specimen extracting device according to an embodiment of the present invention. [Figure 6] 3 is a diagram showing the structure of the waste liquid station in FIG. 2. FIG. DETAILED DESCRIPTION OF THE INVENTION
[0022] The technical means of the embodiments of the present invention will be described below clearly and completely with reference to the drawings in the embodiments of the present invention. However, it goes without saying that the embodiments described below are only some of the embodiments of the present invention, not all of the embodiments of the present invention. The following description of at least one exemplary embodiment is for illustrative purposes only and does not impose any limitations on the present invention and its applications or uses. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative labor fall within the protection scope of the present invention.
[0023] As shown in FIGS. 1 to 6, an embodiment of the present invention provides a specimen extraction device including a specimen loading area 10, a sample reaction area 20, a sample addition area 30, and a grabbing area 40. The sample loading area 10 is provided with a sample loading section 11 for storing and processing sample tubes, the sample reaction area 20 is provided with a sample reaction section 21 for extracting nucleic acids from the sample, the sample addition area 30 is provided with a sample addition section 31 for transferring the sample from the sample loading section 11 to a first reaction vessel and adding the nucleic acid extracted in the sample reaction section 21 to a second reaction vessel, and the grabbing area 40 is provided with a grabbing section 41 for moving the first reaction vessel to which the sample has been added from the sample addition section 31 to the sample reaction section 21 and moving the nucleic acid extracted from the sample from the sample reaction section 21 to the sample addition section 31.Of these, the sample loading area 10, the sample addition area 30 and the grabbing area 40 are all located around the outside of the sample reaction area 20, and the grabbing area 40 is located on the same side as the sample loading area 10, the sample reaction area 20 and the sample addition area 30.
[0024] By applying the technical means of the present invention, the sample extraction device includes a sample loading area 10, a sample reaction area 20, a sample addition area 30 and a grabbing area 40.
[0025] The sample loading area 10 is provided with a sample loading section 11 capable of loading and processing a sample tube containing a sample, the sample addition area 30 is provided with a sample addition section 31 capable of transferring the sample from the sample loading section 11 to a first reaction vessel, and the gripping area 40 is provided with a gripping section 41 capable of moving the first reaction vessel containing the sample from the sample addition section 31 to the sample reaction section 21 of the sample reaction area 20. Nucleic acid can be extracted from the sample using the sample reaction section 21, and the gripping section 41 can be used to move the first reaction vessel after nucleic acid extraction from the sample reaction section 21 to the sample addition section 31, and the nucleic acid extracted in the sample reaction section 21 can be added to a second reaction vessel, thereby replicating the nucleic acid. The sample loading area 10, sample addition area 30, and gripping area 40 are all located outside the sample reaction area 20, and the gripping area 40 is located on the same side as the sample loading area 10, sample reaction area 20, and sample addition area 30. Therefore, the layout between the modules of the specimen extraction device becomes more compact, and the layout of the integrated nucleic acid detection device also becomes more compact, so that the footprint of the integrated nucleic acid detection device becomes smaller.
[0026] In this embodiment, the sample reaction section 21 includes an extraction mechanism, and nucleic acid can be extracted from the sample in the first reaction container by using the extraction mechanism.
[0027] Between the respective areas of the specimen extraction device, a transfer mechanism is provided to realize the transfer of consumables and specimens between the respective areas.
[0028] As shown in Figures 1 to 3 and 5, the specimen extraction device further includes a specimen tube transfer member 50, a reaction vessel transfer member, and an extraction mechanism transfer member 80, wherein the specimen tube transfer member 50 is movably arranged between the specimen loading region 10 and the sample addition region 30 so as to move the specimen tube in the specimen loading region 10 to the sample addition region 30, the reaction vessel transfer member is movably arranged between the sample addition region 30 and the grabbing region 40 so as to move the first reaction vessel and the second reaction vessel in the sample addition region 30 between the sample addition region 30 and the grabbing region 40, and the extraction mechanism transfer member 80 is movably arranged between the sample reaction region 20 and the grabbing region 40 so as to move the first reaction vessel between the sample reaction region 20 and the grabbing region 40. The specimen tube transfer member 50 can be used to transfer the specimen tube from the specimen loading region 10 to the sample addition region 30, and further transfer the specimen to the sample addition region 30 to transfer the specimen to the first reaction vessel. The reaction vessel transfer member can be used to transfer the first reaction vessel between the sample addition region 30 and the grabbing region 40, and the first reaction vessel containing the specimen can be moved from the sample addition region 30 to the grabbing region 40. The extraction mechanism transfer member 80 can be used to transfer the first reaction vessel containing the specimen from the grabbing region 40 to the sample reaction region 20, and nucleic acid can be extracted from the specimen using the sample reaction unit 21. The extraction mechanism transfer member 80 can then be used to transfer the first reaction vessel after nucleic acid extraction from the sample reaction region 20 to the grabbing region 40, and the reaction vessel transfer member can then be used to transfer the first reaction vessel after nucleic acid extraction from the grabbing region 40 to the sample addition region 30, and the extracted nucleic acid can be transferred from the first reaction vessel to the second reaction vessel.
[0029] As shown in Figures 1 and 5, the specimen tube transfer member 50 is movably disposed between the specimen loading area 10 and the sample application area 30 along a first horizontal direction, the reaction vessel transfer member is movably disposed between the sample application area 30 and the grabbing area 40 along a second horizontal direction, and the extraction mechanism transfer member 80 is movably disposed between the sample reaction area 20 and the grabbing area 40 along the second horizontal direction, the first horizontal direction and the second horizontal direction being perpendicular to each other. By moving the specimen tube transfer member 50 along the first horizontal direction and the reaction vessel transfer member and the extraction mechanism transfer member 80 along the second horizontal direction, the movement paths of the specimen tube transfer member 50, the reaction vessel transfer member, and the extraction mechanism transfer member 80 can be shortened, further reducing the space occupied and the footprint of the nucleic acid integrated system.
[0030] As shown in Figures 1 and 2, the reaction vessel transfer member includes a first reaction vessel transfer member 60 and a second reaction vessel transfer member 70 arranged in parallel, and the first reaction vessel transfer member 60 and the second reaction vessel transfer member 70 are both arranged movably along a second horizontal direction between the sample addition area 30 and the grabbing area 40, and the sample addition section 31 includes a liquid transfer needle 311 movably arranged above the first reaction vessel transfer member 60 and the second reaction vessel transfer member 70, and the first reaction vessel transfer section 60 has a sample addition position located in the sample addition area 30, and when the first reaction vessel transfer member 60 is located at the sample addition position, the liquid transfer needle 311 can move above the first reaction vessel transfer member 60 to inject a sample into the first reaction vessel. The liquid transfer needle 311 can be used to aspirate the sample from the sample tube and release it into the first reaction vessel in the first reaction vessel transfer member 60, and the first reaction vessel into which the sample has been injected can be moved from the sample addition area 30 to the grabbing area 40 using the first reaction vessel transfer member 60.
[0031] In this embodiment, the sample extraction device has a frame body, and the sample loading section 11, sample reaction section 21, sample addition section 31 and grabbing section 41 are all arranged within the frame body, the sample addition section 31 further includes a sample arm that is arranged to be movable along the horizontal direction on the frame body, and the liquid transfer needle 311 is arranged to be movable vertically on the sample arm, further realizing three-axis movement of the liquid transfer needle 311.
[0032] Specifically, the second reaction vessel transfer member 70 is located in the sample addition region 30 and has a nucleic acid addition position that is flush with the first reaction vessel transfer member 60. When the first reaction vessel transfer member 60 is located at the sample addition position and the second reaction vessel transfer member 70 is located at the nucleic acid addition position, the liquid transfer needle 311 can move above the first reaction vessel transfer member 60 to aspirate the extracted nucleic acid and move above the second reaction vessel transfer member 70 to transfer the extracted nucleic acid to a second reaction vessel. The liquid transfer needle 311 can be used to transfer the nucleic acid extracted in the sample reaction unit 21 to a second reaction vessel located in the second reaction vessel transfer member 70, and the nucleic acid can then be replicated using an amplification reagent in the second reaction vessel.
[0033] The specimen tube transfer member 50 has a first working position located in the sample application area 30. When the specimen tube transfer member 50 is located in the first working position, the liquid transfer needle 311 can move above the specimen tube transfer member 50 to aspirate the specimen. The specimen tube is transferred from the specimen loading area 10 to the sample application area 30 using the specimen tube transfer member 50, and the liquid transfer needle 311 is used to aspirate the specimen in the specimen tube at the specimen tube transfer member 50 and inject it into the first reaction vessel at the first reaction vessel transfer member 60.
[0034] In this embodiment, by installing a reaction vessel transfer member, a sample addition function of injecting a specimen from a specimen tube into a first reaction vessel and a nucleic acid transfer function of injecting extracted nucleic acid from the first reaction vessel into a second reaction vessel can be realized in one sample addition area 30, which is advantageous for simplifying the structure of the specimen extraction device.
[0035] As shown in FIG. 2, the specimen loading section 11 includes a specimen tube gripper 111 and a specimen bin 112 for storing specimen tubes. The specimen tube gripper 111 is movably disposed above the specimen bin 112 and the specimen tube transfer member 50. The specimen tube transfer member 50 further has a second working position located in the specimen loading area 10. When the specimen tube transfer member 50 is located in the second working position, the specimen tube gripper 111 can transfer the specimen tube from the specimen bin 112 to the specimen tube transfer member 50. The specimen tube gripper 111 can be used to transfer the specimen tube in the specimen bin 112 to the specimen tube transfer member 50. Furthermore, the specimen tube transfer member 50 can be used to transfer the specimen tube between the specimen loading area 10 and the sample addition area 30.
[0036] In this embodiment, the specimen tube gripper 111 can achieve three-axis movement on the frame to transfer the specimen tube from the specimen bottle 112 to the specimen tube transfer member 50. The frame is provided with horizontal and vertical guide rails, and the specimen tube gripper 111 includes a gripper frame and locking claws that are movably mounted on the gripper frame along the vertical direction. The gripper frame can move along the extension directions of the horizontal and vertical guide rails, allowing the gripper frame to move in a horizontal plane and also allowing the locking claws to move along three axes.
[0037] Specimens include samples, quality control specimens, calibration specimens, and the like. 1 and 2, the gripping unit 41 includes a reaction vessel gripper 411 movable in a first horizontal direction and a first vertical direction, and the extraction mechanism transfer member 80 has a receiving position located in the gripping region 40 and an extraction position located in the sample reaction region 20. The reaction vessel transfer member has a first transfer position located in the gripping region 40. When the reaction vessel transfer member is located at the first transfer position and the extraction mechanism transfer member 80 is located at the receiving position, the reaction vessel gripper 411 can grip the first reaction vessel and move it between the reaction vessel transfer member and the extraction mechanism transfer member 80. The reaction vessel gripper 411 can be used to move the first reaction vessel containing a sample from the reaction vessel transfer member to the extraction mechanism transfer member 80, and the extraction mechanism transfer member 80 can move the first reaction vessel from the gripping position to the extraction position to transfer the first reaction vessel into the extraction mechanism, thereby extracting nucleic acid from the sample. After nucleic acid extraction, the first reaction vessel after nucleic acid extraction can be moved from the extraction position to the gripping position using the extraction mechanism transfer member 80, and the first reaction vessel can be moved from the extraction mechanism transfer member 80 to the reaction vessel transfer member using the reaction vessel gripper 411.
[0038] In this embodiment, the first reaction vessel transfer member 60 can be positioned at a first transfer position, and the reaction vessel gripper 411 grabs the first reaction vessel and moves the first reaction vessel between the first reaction vessel transfer member 60 and the extraction mechanism transfer member 80.
[0039] In this embodiment, the transfer member that moves horizontally between areas and the gripper that can move horizontally and vertically within the area work together to transport consumables between each area, and each area can operate independently and in parallel, realizing a compact structure while ensuring work efficiency.
[0040] Specifically, the specimen loading unit 11 further includes a cover opening member 12, and the specimen tube transfer member 50 further has a third working position. When the specimen tube transfer member 50 is located in the third working position, the specimen tube transfer member 50 is located below the cover opening member 12, and the third working position is located between the first and second working positions. The cover opening member 12 can be used to open the specimen tube located on the specimen tube transfer member 50 so that the sample adding unit 31 can aspirate the specimen in the specimen tube.
[0041] In this embodiment, the frame is provided with a container gripper guide rail extending along a first horizontal direction, and the reaction container gripper 411 includes a container gripper frame movably mounted on the container gripper guide rail along the extension direction of the container gripper guide rail, and an orifice plate locking claw movably mounted on the container gripper frame in the vertical direction. By adopting the above-described structure, it is possible to realize biaxial movement of the reaction container gripper 411.
[0042] Specifically, both the first reaction vessel transfer member 60 and the extraction mechanism transfer member 80 can be moved to the gripping area 40, and furthermore, the reaction vessel gripper 411 can be used to move the first reaction vessel into which the sample has been injected from the first reaction vessel transfer member 60 to the extraction mechanism transfer member 80. Furthermore, the first reaction vessel can be moved to the extraction position by the extraction mechanism transfer member 80, and nucleic acid extraction can be performed using the extraction mechanism.
[0043] 2, the sample application unit 31 further includes a consumable storage bin 312 for placing the liquid transfer head thereon, and the liquid transfer needle 311 can move above the consumable storage bin 312 to load the liquid transfer head. The consumable storage bin 312 can be used to store the liquid transfer head, and the liquid transfer needle 311 can be further used to load the liquid transfer head.
[0044] Specifically, before the liquid transfer needle 311 aspirates the sample in the sample tube, the liquid transfer needle 311 must be moved above the consumables storage bin 312 to load the liquid transfer head. Then, the sample is aspirated using the liquid transfer head. The process of aspirating nucleic acids is similar, so a detailed description will be omitted here.
[0045] In this embodiment, the gripping area 40 is further provided with a film sealing mechanism 43, and the reaction vessel transfer member further has a second transfer position located in the gripping area 40. When the reaction vessel transfer member is located at the second transfer position, the reaction vessel gripper 411 can move above the reaction vessel transfer member to grip the second reaction vessel loaded with nucleic acid, and move above the film sealing mechanism 43 to release the second reaction vessel into the film sealing mechanism 43. The reaction vessel gripper 411 can be used to transfer the second reaction vessel loaded with nucleic acid to the film sealing mechanism 43, and the film sealing mechanism 43 can be used to seal the second reaction vessel loaded with nucleic acid.
[0046] Specifically, the second reaction vessel transfer member 70 can be positioned at a second transfer position, and the reaction vessel gripper 411 can move above the second reaction vessel transfer member 70 to grab the second reaction vessel loaded with nucleic acid.
[0047] 1, 2, and 4, the film sealing mechanism 43 includes a heat press member 431 and a film sealing mechanism transfer member 432. The film sealing mechanism transfer member 432 is provided below the heat press member 431 so as to be movable along a second horizontal direction. The film sealing mechanism transfer member 432 has a lid body placement position 433 for placing a lid body and a second reaction container placement position 434 for placing a second reaction container. The reaction container gripper 411 can release the second reaction container to the second reaction container placement position 434. Reaction vessel gripper 411 has a gripping position located above film sealing mechanism transfer member 432, and when reaction vessel gripper 411 is located at the gripping position, film sealing mechanism transfer member 432 has a separation position where lid body placing position 433 moves below reaction vessel gripper 411 so that reaction vessel gripper 411 grips the lid body, a release position where second reaction vessel placing position 434 moves below reaction vessel gripper 411 so that reaction vessel gripper 411 releases the lid body onto the second reaction vessel, and a sealing position where second reaction vessel placing position 434 moves below heat press member 431. By employing the above-described structure, the lid body can be placed using lid body placing position 433 of film sealing mechanism transfer member 432, and the second reaction vessel placing position 434 can be placed using the second reaction vessel placing position.
[0048] Then, the reaction vessel gripper 411 is used to move the second reaction vessel containing and loaded with nucleic acid to the film sealing mechanism transfer member 432, and the lid is moved from the lid placement position 433 to the second reaction vessel, and the heat press member 431 is used to complete the sealing of the lid and the second reaction vessel.
[0049] 2 and 6, the gripping area 40 further includes a waste liquid station 42 located below the reaction vessel gripper 411. The waste liquid station 42 includes a waste liquid frame 421, a tray 422, and a waste liquid collection member 423. The waste liquid collection member 423 is movably mounted on the waste liquid frame 421 along the vertical direction and the second horizontal direction. When the first reaction vessel transfer member 60 is located at the second transfer position, the reaction vessel gripper 411 can move above the first reaction vessel transfer member 60 to grab the first reaction vessel and move above the tray 422 to release the first reaction vessel onto the tray 422. The waste liquid collection member 423 can move above the tray 422 to collect the magnetic rod cover and waste liquid. The reaction vessel gripper 411 can be used to transfer the first reaction vessel in the first reaction vessel transfer member 60 after nucleic acid extraction to a tray 422, and the waste liquid and magnetic rod cover in the first reaction vessel can be collected using the waste liquid collection member 423.
[0050] In this embodiment, a protrusion is provided at the upper end of the waste liquid collection member 423, which can be used to collect the magnetic rod cover, and a waste liquid needle is provided at the lower end of the waste liquid collection member 423, which can be used to suck up the waste liquid.
[0051] As shown in FIG. 6 , the waste liquid station 42 further includes a support plate 424, a push rod 425, and a collection box. The collection box is located below the waste liquid frame 421. The tray 422 is mounted on the waste liquid frame 421 so as to be vertically movable. The push rod 425 is mounted on the support plate 424 so as to be movable along a second horizontal direction. The support plate 424 has an evacuation opening for retracting the tray 422. The tray 422 can move below the support plate 424 to place a first reaction vessel on the support plate 424. The push rod 425 can push the first reaction vessel to collect the first reaction vessel in the collection box. The tray 422 can be retracted using the evacuation opening of the support plate 424, and the first reaction vessel on the tray 422 can be placed on the support plate 424. The push rod 425 can be used to move the first reaction vessel from the support plate 424 to the collection box.
[0052] Specifically, after nucleic acid extraction, the first reaction vessel is transferred to tray 422 using reaction vessel gripper 411, and then waste liquid collection member 423 is used to move the first reaction vessel above it, thereby recovering the magnetic rod cover and waste liquid. After recovering the magnetic rod cover and waste liquid, tray 422 is moved vertically to pass through the evacuation opening, thereby placing the first reaction vessel on support plate 424, and push rod 425 can be used to move the first reaction vessel on support plate 424 to a collection box.
[0053] In this embodiment, when extracting nucleic acids from a sample, the sample tube gripper 111 is used to move above the sample bottle 112 to grab the sample tube and move it to the sample tube transfer member 50 located at the second working position. The sample tube is then moved by the sample tube transfer member 50 to the third working position located below the lid-opening member 12, where it is opened using the lid-opening member 12. After the lid is opened, the sample tube is moved to the first working position located at the sample addition area 30 on the sample tube transfer member 50. The liquid transfer needle 311 is then used to move the sample above the sample tube transfer member 50 and aspirate the sample. The liquid transfer needle 311 is then moved to the sample addition area 30 and above the first reaction vessel transfer member 60 located at the sample addition position, where the liquid transfer needle 311 is used to release the sample into the first reaction vessel in the first reaction vessel transfer member 60. The first reaction vessel transfer member 60 is then moved to a first transfer position located in the gripping region 40, and the reaction vessel gripper 411 is used to grip the first reaction vessel on the first reaction vessel transfer member 60. The reaction vessel gripper 411 is then moved above the extraction mechanism transfer member 80 located at the receiving position, and the first reaction vessel is released to the extraction mechanism transfer member 80. The extraction mechanism transfer member 80 is then moved to an extraction position located in the extraction mechanism, and nucleic acid in the sample is extracted using the extraction mechanism. After nucleic acid extraction, the extraction mechanism transfer member 80 is moved from the extraction position located in the sample reaction region to a receiving position located in the gripping region 40, and the reaction vessel gripper 411 is used to grip the first reaction vessel and release it to the first reaction vessel transfer member 60 located at the first transfer position. Furthermore, the first reaction vessel transfer member 60 is moved to a sample addition position located in the sample addition area 30, and the extracted nucleic acid in the first reaction vessel is aspirated using the liquid transfer needle 311, and the liquid transfer needle 311 is further moved above the second reaction vessel transfer member 70 located at the nucleic acid addition position, thereby releasing the nucleic acid into the second reaction vessel.Furthermore, the second reaction vessel transfer member 70 is moved to a second transfer position located in the gripping area 40, the second reaction vessel is gripped using the reaction vessel gripper 411, the reaction vessel gripper 411 is moved to a gripping position located above the film sealing mechanism transfer member 432, the second reaction vessel is released to the second reaction vessel loading position 434, and the film sealing mechanism transfer member 432 is moved to a separation position, the reaction vessel gripper 411 is used to grip the lid body, the film sealing mechanism transfer member 432 is further moved to a release position to release the lid body onto the second reaction vessel, the film sealing mechanism transfer member 432 is moved to a sealing position, and the lid body and the second reaction vessel are sealed using a heat press member 431.
[0054] Among these, the first horizontal direction refers to the X-axis direction in FIG. 2, the second horizontal direction refers to the Y-axis direction in FIG. 2, and the vertical direction refers to the Z-axis direction in FIG.
[0055] Another embodiment of the present invention provides an integrated nucleic acid detection apparatus including a reagent preparation apparatus, a sample extraction apparatus, and an amplification apparatus, wherein the reagent preparation apparatus is for preparing extraction reagents and amplification reagents, the amplification apparatus is for performing an analyte detection measurement on the measurement mixture to analyze the sample, and the sample extraction apparatus is the sample extraction apparatus provided above. When this integrated nucleic acid detection apparatus is used, the sample loading area 10, the sample addition area 30, and the gripping area 40 are all arranged around the outside of the sample reaction area 20, so that the gripping area 40 is located on the same side as the sample loading area 10, the sample reaction area 20, and the sample addition area 30. This allows for a more compact layout between the modules of the sample extraction apparatus, and also allows for a more compact layout of the integrated nucleic acid detection apparatus.
[0056] In this embodiment, the reagent preparation device, sample extraction device, and amplification device are isolated from each other, and the reagent preparation device and amplification device are located on either side of the sample extraction device. A first passage is provided between the reagent preparation device and the sample extraction device, and a second passage is provided between the sample extraction device and the amplification device, with both the first passage and the second passage having a blocked state and a conductive state. By adopting this structure, the isolation of the first and second passages can be used to achieve isolation between each device module and prevent cross-contamination. The conductivity of the first and second passages can be used to achieve the transfer of consumables between each device module.
[0057] The integrated nucleic acid detection device further includes a transfer mechanism provided between the reagent preparation device and the specimen extraction device, and the transfer mechanism can move a first reaction vessel in which an extraction reagent is prepared and a second reaction vessel in which an amplification reagent is prepared to the specimen extraction device through a first passage, and the gripping unit 41 of the specimen extraction device can move the first reaction vessel to a first reaction vessel position in the specimen extraction device and move the second reaction vessel to a second reaction vessel position in the specimen extraction device. Using the transfer mechanism, the first reaction vessel in which the extraction reagent has been prepared in the reagent preparation device and the second reaction vessel in which the amplification reagent has been prepared can be moved to the specimen extraction device to perform specimen extraction.
[0058] It should be noted that the terms used herein are merely for the purpose of describing specific embodiments and are not intended to limit the exemplary embodiments of the present application. As used herein, the singular also includes the plural unless expressly stated otherwise. Furthermore, when the terms "comprise" and / or "include" are used herein, it should be understood to specify the presence of features, steps, operations, devices, components, and / or combinations thereof.
[0059] Unless otherwise specified, the relative arrangement of components and steps, formulas, and numerical values described in these examples do not limit the scope of the present invention. It should be understood that, for convenience of explanation, the dimensions of each part shown in the drawings are not drawn according to actual proportional relationships. Techniques, methods, and devices known to those skilled in the art may not be discussed in detail; however, where appropriate, such techniques, methods, and devices should be considered part of the specification. In all examples illustrated and discussed herein, any specific values should be construed as illustrative only and not limiting. Therefore, examples other than the illustrative examples may have different values. Note that similar symbols and letters indicate similar objects in the following drawings, and once any one is defined in one drawing, further discussion in subsequent drawings is unnecessary.
[0060] In describing the present invention, orientations or positional relationships indicated by directional terms such as "front, rear, top, bottom, left, right," "lateral, longitudinal, vertical, horizontal," and "top, bottom" are generally based on the orientations or positional relationships shown in the drawings and are merely for the convenience and simplification of the description of the present invention. Unless otherwise stated, these directional terms do not indicate or imply that the indicated devices or elements have a specific orientation or must be configured and operated in a specific orientation, and therefore should not be understood as limiting the scope of protection of the present invention. The directional terms "inside, outside" mean inside and outside relative to the contour of each member itself.
[0061] For convenience of description, relative spatial terms, such as "above," "above," "on top of," or "above," may be used to describe the spatial relationship of one device or feature shown in a figure to another. Relative spatial terms are intended to encompass different orientations of the device during use or operation other than the illustrated orientation. For example, if a device is inverted in a figure, a device described as "above other devices or structures" or "on top of other devices or structures" would then be positioned as "below other devices or structures" or "beneath other devices or structures." Thus, the exemplary term "above" encompasses two orientations: "above" and "below." The device may be positioned in other different ways (rotated 90 degrees or at other orientations) and the spatial descriptions used herein interpreted accordingly.
[0062] It should be noted that the use of terms such as "first" and "second" to define parts is merely to facilitate the distinction between corresponding parts, and unless otherwise specified, the above terms have no special meaning and should not be understood as limiting the scope of protection of the present invention.
[0063] The above is only a preferred embodiment of the present invention, and does not limit the present invention. Those skilled in the art can make various modifications and changes to the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention. [Explanation of symbols]
[0064] 10: sample loading area, 11: sample loading section, 111: sample tube gripper, 112: sample bottle, 12: lid opening member, 20: sample reaction area, 21: sample reaction section, 30: sample addition area, 31: sample addition section, 311: liquid transfer needle, 312: consumables storage bottle, 40: gripping area, 41: gripping portion, 411: reaction vessel gripper, 42: waste liquid station, 421: waste liquid frame, 422: tray, 423: waste liquid recovery member, 424: support plate, 425: push rod, 43: film sealing mechanism, 431: heat press member, 432: film sealing mechanism transfer member, 433: lid body placement position, 434: second reaction vessel placement position, 50: specimen tube transfer member, 60: first reaction vessel transfer member, 70: second reaction vessel transfer member, 80: Extraction mechanism transfer member.
Claims
1. a sample loading area (10) provided with a sample loading section (11) for storing and processing sample tubes; a sample reaction area (20) provided with a sample reaction section (21) for extracting nucleic acid from a specimen; a sample addition area (30) provided with a sample addition section (31) for transferring a sample from the sample loading section (11) to a first reaction vessel and adding nucleic acid extracted in the sample reaction section (21) to a second reaction vessel; a grasping region (40) provided with a grasping section (41) for moving the first reaction vessel after adding a specimen from the sample addition section (31) to the sample reaction section (21) and for moving the first reaction vessel after extracting nucleic acid from the specimen from the sample reaction section (21) to the sample addition section (31); The specimen loading area (10), the sample addition area (30), and the gripping area (40) are all arranged around the outside of the sample reaction area (20), and the gripping area (40) is located on the same side as the specimen loading area (10), the sample reaction area (20), and the sample addition area (30); The apparatus further includes a specimen tube transfer member (50), a reaction vessel transfer member, and an extraction mechanism transfer member (80), the specimen tube transfer member (50) is movably provided between the specimen loading area (10) and the sample application area (30) so as to transfer the specimen tube in the specimen loading area (10) to the sample application area (30); the reaction vessel transferring member is provided movably between the sample application area (30) and the gripping area (40) so as to move the first reaction vessel and the second reaction vessel in the sample application area (30) between the sample application area (30) and the gripping area (40); the extraction mechanism transfer member (80) is movably provided between the sample reaction area (20) and the gripping area (40) so as to move the first reaction vessel between the sample reaction area (20) and the gripping area (40); The sample loading section (11) includes a sample tube gripper (111) and a sample bottle (112) for storing the sample tubes; the specimen tube gripper (111) is movably provided above the specimen bottle (112) and the specimen tube transfer member (50); The sample tube transfer member (50) further has a second working position located in the sample loading area (10); A specimen extraction device characterized in that, when the specimen tube transfer member (50) is located in the second working position, the specimen tube gripper (111) can move the specimen tube from the specimen bottle (112) to the specimen tube transfer member (50).
2. The specimen tube transfer member (50) is provided between the specimen loading area (10) and the sample addition area (30) so as to be movable along a first horizontal direction; the reaction vessel transfer member is provided between the sample addition area (30) and the gripping area (40) so as to be movable along a second horizontal direction; the extraction mechanism transfer member (80) is provided between the sample reaction area (20) and the gripping area (40) so as to be movable along the second horizontal direction; 2. The specimen extraction device according to claim 1, wherein the first horizontal direction and the second horizontal direction are perpendicular to each other.
3. The reaction vessel transfer member includes a first reaction vessel transfer member (60) and a second reaction vessel transfer member (70) that are arranged in parallel, the first reaction vessel transfer member (60) and the second reaction vessel transfer member (70) are both provided between the sample addition area and the gripping area so as to be movable along a second horizontal direction; the sample addition section (31) includes a liquid transfer needle (311) movably provided above the first reaction vessel transfer member (60) and the second reaction vessel transfer member (70); the first reaction vessel transfer section (60) has a sample application position located in the sample application area (30); When the first reaction vessel transfer member (60) is located at the sample addition position, the liquid transfer needle (311) can move above the first reaction vessel transfer member (60) to inject the sample into the first reaction vessel; the second reaction vessel transfer member (70) has a nucleic acid addition position that is located in the sample addition region (30) and is flush with the first reaction vessel transfer member (60); The specimen extraction device of claim 2, characterized in that, when the first reaction vessel transfer member (60) is located at the sample addition position and the second reaction vessel transfer member (70) is located at the nucleic acid addition position, the liquid transfer needle (311) can move above the first reaction vessel transfer member (60) to aspirate the extracted nucleic acid and move above the second reaction vessel transfer member (70) to transfer the extracted nucleic acid to the second reaction vessel.
4. The specimen tube transfer member (50) has a first working position located in the sample application area (30), 4. The specimen extraction device according to claim 3, wherein when the specimen tube transfer member (50) is located in the first working position, the liquid transfer needle (311) can move above the specimen tube transfer member (50) to aspirate the specimen.
5. The gripping unit (41) includes a reaction vessel gripper (411) that is movable in a first horizontal direction and a first vertical direction, The extraction mechanism transfer member (80) has a receiving position located in the gripping area (40) and an extraction position located in the sample reaction area (20); the reaction vessel transfer member has a first transfer position located in the gripping area (40); 2. The specimen extraction device of claim 1, wherein when the reaction vessel transfer member is located at the first transfer position and the extraction mechanism transfer member is located at the receiving position, the reaction vessel gripper can grab the first reaction vessel and move the first reaction vessel between the reaction vessel transfer member and the extraction mechanism transfer member.
6. The sample application section (31) further includes a consumables storage bottle (312) for placing a liquid transfer head thereon; 4. The specimen extraction device of claim 3, wherein the liquid transfer needle (311) can be moved above the consumable storage bin (312) to load a liquid transfer head.
7. The gripping area (40) is further provided with a film sealing mechanism (43) for sealing the second reaction vessel; the reaction vessel transfer member further has a second transfer position located in the gripping area (40); The sample extraction device described in claim 5, characterized in that when the reaction vessel transfer member is located at the second transfer position, the reaction vessel gripper (411) can move above the reaction vessel transfer member to grab the second reaction vessel after nucleic acid loading, and move above the film sealing mechanism (43) to release the second reaction vessel into the film sealing mechanism (43).
8. The film sealing mechanism (43) includes a heat press member (431) and a film sealing mechanism transfer member (432), The film sealing mechanism transfer member (432) is provided below the heat press member (431) so as to be movable along a second horizontal direction, The film sealing mechanism transfer member (432) has a lid body placement position (433) for placing a lid body and a second reaction vessel placement position (434) for placing a second reaction vessel, the reaction vessel gripper (411) is capable of releasing the second reaction vessel to the second reaction vessel placement position (434); The reaction vessel gripper (411) has a gripping position located above the film sealing mechanism transfer member (432), The specimen extraction device of claim 7, wherein, when the reaction vessel gripper (411) is located at the gripping position, the film sealing mechanism transfer member (432) has a separation position in which the lid body placing position (433) moves below the reaction vessel gripper (411) so that the reaction vessel gripper (411) grasps the lid body, a release position in which the second reaction vessel placing position (434) moves below the reaction vessel gripper (411) so that the reaction vessel gripper (411) releases the lid body into the second reaction vessel, and a sealing position in which the second reaction vessel placing position (434) moves below the heat press member (431).
9. The gripping area (40) further comprises a waste station (42) located below the reaction vessel gripper (411); The waste liquid station (42) includes a waste liquid frame (421), a tray (422), and a waste liquid collecting member (423); the waste liquid collecting member (423) is provided on the waste liquid frame (421) so as to be movable along a vertical direction and a second horizontal direction; When the reaction vessel transfer member is located at the first transfer position, the reaction vessel gripper (411) can move above the first reaction vessel transfer member (60) to grab a first reaction vessel, and move above the tray (422) to release the first reaction vessel onto the tray (422); 6. The specimen extraction device according to claim 5, wherein the waste liquid collecting member (423) can move above the tray (422) to collect the magnetic rod cover and the waste liquid.
10. The waste station (42) further includes a support plate (424), a push rod (425), and a collection box; The collection box is located below the waste liquid frame (421), The tray (422) is provided in the waste liquid frame (421) so as to be movable in the vertical direction, The push rod (425) is provided on the support plate (424) so as to be movable along the second horizontal direction, The support plate (424) has an evacuation opening for evacuating the tray (422), the tray (422) can be moved below the support plate (424) to deposit a first reaction vessel on the support plate (424); 10. The specimen extraction device according to claim 9, wherein the push rod (425) can push the first reaction container to collect the first reaction container into the collection box.
11. a reagent preparation device for preparing extraction reagents and amplification reagents; an amplification device for performing an analyte detection assay on the assay mixture to analyze the analyte; An integrated nucleic acid detection device comprising: the specimen extraction device according to any one of claims 1 to 10.
12. the reagent preparation device, the test substance extraction device, and the amplification device are isolated from each other; the reagent preparation device and the amplification device are located on either side of the sample extraction device, a first passage is provided between the reagent preparation device and the sample extraction device, and a second passage is provided between the sample extraction device and the amplification device, and both the first passage and the second passage have a blocking state and a conducting state; and / or a transfer mechanism provided between the reagent preparation device and the specimen extraction device; the transfer mechanism can move a first reaction vessel for preparing an extraction reagent and a second reaction vessel for preparing an amplification reagent to the specimen extraction device through the first passage; The integrated nucleic acid detection device of claim 11, characterized in that the gripping portion (41) of the sample extraction device can move the first reaction vessel to a first reaction vessel placement position of the sample extraction device and move the second reaction vessel to a second reaction vessel placement position of the sample extraction device.
Citation Information
Patent Citations
Device and method for liquid transfer type nucleic acid extraction
CN108998444A
Automatic nucleic acid extractor
CN111621418A
Nucleic acid extraction device
JP2014020779A
Nucleic acid analyzer
JP2019054826A
Specimen pretreatment device, robot arm, and specimen pretreatment method
JP2019174369A