WO2015192331A1 - 核酸提取装置及其工作方法 - Google Patents

核酸提取装置及其工作方法 Download PDF

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Publication number
WO2015192331A1
WO2015192331A1 PCT/CN2014/080130 CN2014080130W WO2015192331A1 WO 2015192331 A1 WO2015192331 A1 WO 2015192331A1 CN 2014080130 W CN2014080130 W CN 2014080130W WO 2015192331 A1 WO2015192331 A1 WO 2015192331A1
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WIPO (PCT)
Prior art keywords
nucleic acid
liquid
incubation
reaction vessel
reaction
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PCT/CN2014/080130
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English (en)
French (fr)
Inventor
王海
翁彦雯
冷彦宁
解传芬
Original Assignee
深圳迈瑞生物医疗电子股份有限公司
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Application filed by 深圳迈瑞生物医疗电子股份有限公司 filed Critical 深圳迈瑞生物医疗电子股份有限公司
Priority to CN201480074410.9A priority Critical patent/CN105940094B/zh
Priority to PCT/CN2014/080130 priority patent/WO2015192331A1/zh
Publication of WO2015192331A1 publication Critical patent/WO2015192331A1/zh
Priority to US15/374,863 priority patent/US10647979B2/en

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/1003—Extracting or separating nucleic acids from biological samples, e.g. pure separation or isolation methods; Conditions, buffers or apparatuses therefor
    • C12N15/1006—Extracting or separating nucleic acids from biological samples, e.g. pure separation or isolation methods; Conditions, buffers or apparatuses therefor by means of a solid support carrier, e.g. particles, polymers
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6844—Nucleic acid amplification reactions
    • C12Q1/6848—Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00584—Control arrangements for automatic analysers
    • G01N35/0092—Scheduling
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/025—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations having a carousel or turntable for reaction cells or cuvettes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/04—Details of the conveyor system
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1002—Reagent dispensers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N2035/00465—Separating and mixing arrangements
    • G01N2035/00534—Mixing by a special element, e.g. stirrer
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N2035/00465—Separating and mixing arrangements
    • G01N2035/00564—Handling or washing solid phase elements, e.g. beads
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/04—Details of the conveyor system
    • G01N2035/0401—Sample carriers, cuvettes or reaction vessels
    • G01N2035/0437—Cleaning cuvettes or reaction vessels
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/04—Details of the conveyor system
    • G01N2035/0439—Rotary sample carriers, i.e. carousels
    • G01N2035/0444—Rotary sample carriers, i.e. carousels for cuvettes or reaction vessels

Definitions

  • the invention relates to the field of nucleic acid extraction technology, and in particular to a nucleic acid extraction device and a working method thereof.
  • Nucleic acid is the basic object of molecular biology research.
  • the nucleic acid extraction step is the most important and basic part of molecular diagnosis.
  • the magnetic bead separation method is one of the most widely used and most mature automation methods.
  • the basic principle is that the surface of small particles with magnetic materials can be adsorbed by a certain treatment, and then adsorbed by magnets.
  • the enriched magnetic beads are cleaned to further remove impurities and other unwanted substances, and the biological material of interest is retained by adsorption on the magnetic beads, and finally enriched in the magnetic beads under certain conditions.
  • the biological material on it is released into the desired solution system.
  • the existing automated nucleic acid extraction equipment using magnetic bead separation method has evolved from a fully automated enzyme-free system, generally referred to as a plate type scheme, that is, a classic 96-well plate or a deformed plate (hereinafter collectively referred to as a 96-well plate).
  • the reagent and the sample liquid are loaded through a plurality of parallel loading heads, and then the whole plate is oscillated and mixed, and after the incubation is completed, it is sent to the magnetic separation position for magnetic adsorption, and a plurality of liquid suction heads are connected in parallel (Tip The operation of sucking the waste liquid is repeated a certain number of times to wash the interfering substances other than the nucleic acid, and then the 96-well plate which has been washed is eluted to obtain an eluted product (i.e., the nucleic acid dispersed in the eluate).
  • an eluted product i.e., the nucleic acid dispersed in the eluate
  • a 96-well plate is usually used in the nucleic acid extraction device to perform processing for each test step for the test unit.
  • cross-infection is sometimes found. It is considered that it is related to the processing of each test step by using a 96-well plate as a test unit in a nucleic acid extraction device. This plate scheme uses multiple methods in parallel.
  • the sample because the pore spacing is small and the depth of the pore is small, it is easy to cause the reaction liquid to enter the surrounding pore position, thereby forming a pollution to the surrounding pore position, and the parallel liquid absorption and drainage treatment of the multi-head is also likely to cause a high risk of cross-contamination. In addition, use the whole plate to shake and mix It is also easy to cause cross-contamination.
  • a nucleic acid extraction apparatus comprising:
  • At least one recyclable annular structure the annular structure being spaced apart from a plurality of reaction cups for carrying a reaction vessel, the annular structure being distributed along the way of its cyclic movement with at least one for performing a pipetting operation and At least one operating position of the infusion operation;
  • At least one liquid absorbing mechanism arranged to perform the liquid absorbing operation along the annular structure; at least one liquid filling mechanism arranged to perform the liquid filling operation along the annular structure; for driving the annular structure to circulate Drive mechanism.
  • a nucleic acid extraction apparatus includes:
  • An incubation mechanism for providing a place for the reaction solution to be incubated
  • a separating mechanism for separating the nucleic acid-binding carrier to which the nucleic acid is adsorbed is separated from the reaction solution, wherein the separating mechanism is the recyclable ring structure, and a plurality of rows arranged at least one column are arranged along the annular interval a reaction cup for carrying the reaction vessel, the separation mechanism is distributed along the way of its cyclic movement with an inlet and outlet position for taking out or placing the reaction vessel from the separation mechanism, at least one liquid absorption position and at least one liquid injection position;
  • At least one liquid suction mechanism for performing a liquid suction operation at a liquid suction position of the separation mechanism; at least one liquid injection mechanism for performing a liquid injection operation at a liquid injection position of the separation mechanism; at least one for transporting the reaction container into and out of each mechanism Transshipment agency.
  • a method for operating a nucleic acid extraction device includes: driving at least one liquid absorbing mechanism when the annular structure drives the reaction container to stop according to a predetermined rotation operation. And the at least one infusion mechanism performs a predetermined operation to each of the reaction vessels located in the operating position, and continues to transport to the next operating position with the annular structure after the reaction vessel completes the predetermined operation.
  • a method for operating a nucleic acid extraction device comprising: driving the separation mechanism to cycle progressively according to a preset rotation step and a rotation direction and during a stop period Perform a predetermined operation when the separation mechanism performs the operation When stopped, the transport mechanism picks up the reaction vessel from which the incubation is completed from the incubation mechanism to the ingress and egress of the separation mechanism, or picks up the completed separation reaction vessel located in the entry and exit position of the separation mechanism.
  • the nucleic acid extraction device uses a recyclable ring structure and performs a liquid absorption and liquid injection operation thereon, and the reaction cup positions are spaced apart so that a single reaction container can be used as a processing unit during nucleic acid extraction. Processing one by one, which can open the gap between test and test, reduce the parallel operation between different tests, and thus effectively solve the cross-contamination problem between tests.
  • FIG. 1 is a schematic plan view of a nucleic acid extraction device according to an embodiment of the present invention
  • FIG. 2 is a schematic perspective view of the separation mechanism of FIG.
  • Figure 3 is a schematic view showing the working process of the separating mechanism shown in Figure 2;
  • Fig. 4 is a flow chart showing the operation of the nucleic acid extraction device according to an embodiment of the present invention. detailed description
  • a nucleic acid extraction device for fully automating a nucleic acid extraction process, that is, a plurality of test steps involved in a nucleic acid extraction process (such as including a dispensing reaction solution, mixing hooks, and incubation) is provided. , magnetic separation and elution, etc. are all automated.
  • the nucleic acid extraction device comprises:
  • the annular structure is spaced apart from a plurality of reaction cups for carrying the reaction vessel, and the annular structure is distributed along the way of its cyclic movement for performing a liquid suction operation or a liquid injection operation
  • the annular structure is a structure that is connected end to end and can be cyclically moved, and the shape thereof is not limited.
  • the annular structure may be a circular running track or a square or serpentine running track;
  • At least one liquid absorbing mechanism arranged to perform a liquid absorbing operation along the annular structure; at least one liquid filling mechanism arranged to perform a liquid filling operation along the annular structure; for driving the reaction vessel located on the annular structure along the annular structure
  • the drive mechanism of the cyclic movement of the movement is not limited to:
  • the liquid that can be injected includes a sample, a reagent, a nucleic acid binding carrier, a cleaning solution, and an eluent, and the injected liquid is associated with a corresponding operation, such as injection in a separation operation. It is the cleaning solution.
  • the injection of the nucleic acid-binding carrier can be dispensed by an additional infusion mechanism that is not disposed along the annular structure but is disposed adjacent thereto.
  • the injection of the eluent may also be dispensed not by the liquid injection mechanism arranged along the annular structure, but by other liquid injection mechanisms additionally arranged in the vicinity of the annular structure.
  • the detection reagent can be directly injected for detection.
  • the annular structure is only one, that is, the annular structure integrates the incubation operation, the separation operation, and the elution operation.
  • the incubation operation involves incubating the reaction solution
  • the separation operation comprises separating the nucleic acid-bound carrier adsorbed with the nucleic acid from the incubated reaction solution
  • the elution operation includes The eluate is added to the separated reaction vessel to form an elution product, and the eluted product may not include the nucleic acid-binding carrier, and may also include a nucleic acid-binding carrier.
  • the annular structure is two, that is, a first annular structure and a second annular structure, and the first annular structure is used to perform any two of an incubation operation, a separation operation, and an elution operation, and the second ring The structure is used to perform the remaining operation.
  • annular structures there are three annular structures, one of which is used to perform the incubation operation, the other is used to perform the separation operation, and the remaining one is used to perform the elution operation.
  • the pipetting mechanism can perform a pipetting operation using a disposable pipetting head. It is easy to understand that the nucleic acid extraction device also needs at least one transport mechanism for transporting the reaction container into and out of the annular structure, and the reaction solution in the reaction container is often required to be mixed in the nucleic acid extraction. Therefore, the nucleic acid extraction device also needs to include at least one The mixer is used to mix the reaction solution in the reaction vessel.
  • the nucleic acid extraction device transfers a flow tube for carrying the waste liquid following the reaction container during the stop of the transport mechanism transport reaction container before performing the elution operation, and the flow tube can also carry the suction tube
  • the liquid head, the flow tube and the reaction vessel are used together to further avoid cross-contamination due to injection or aspiration. It is easy to understand that a flow tube position can be provided on the ring structure, and the flow tube position is adjacent to the reaction cup position.
  • the reaction cups carrying the reaction container are disposed at intervals on the recyclable annular structure, and operations such as liquid absorption and liquid injection are performed on the annular structure.
  • the working method is: when the driving annular structure drives the reaction container to stop according to the pre-shaped structure, the at least one liquid suction mechanism and the at least one liquid injection mechanism perform a predetermined operation to the reaction container located in the operating position, when the reaction container After the predetermined operation is completed, the transfer continues with the ring structure. It can be seen that it is different from the traditional plate structure because the whole plate is the processing unit.
  • the cross-contamination caused by the processing of the nucleic acid extraction device of the present embodiment is performed by processing the nucleic acid extraction one by one with a single reaction container as a processing unit, and the single-stage sequential treatment can open the test and test.
  • the distance between the two tests reduces the parallel operation between different tests, which can effectively solve the cross-contamination problem between tests.
  • a nucleic acid extraction apparatus comprising: an incubation mechanism, a separation mechanism, an elution mechanism, a liquid absorption mechanism, a liquid injection mechanism, and at least one transport mechanism for transporting the reaction container into and out of each mechanism.
  • the nucleic acid extraction and detection are separated, and the nucleic acid extraction is described by three test steps of incubation, separation and elution. In another example, nucleic acid extraction may also be performed without elution, and incubation and separation are performed.
  • the detection reagent can also be directly injected for detection.
  • a configuration a plurality of reaction cups arranged in at least one column for carrying the reaction vessel are arranged along the annular space, and the incubation mechanism is distributed along the path of the circulation movement for removing the reaction container from the incubation mechanism for mixing A mixing hook is used to place the reaction vessel into the placement position of the incubation mechanism, the sample addition site, and the reagent addition site.
  • the nucleic acid extraction device further includes an incubation mixer, and the injection mechanism includes a sample addition mechanism and a reagent addition mechanism. The incubation mechanism is cycled according to a preset rotation step and a rotation direction.
  • the transport mechanism picks up the reaction container located at the mixing position of the incubation mechanism to the incubation mixer or mixes the incubation
  • the reaction container in the device is picked up to the mixing hook
  • the transport mechanism picks up the empty reaction container to the loading position of the incubation mechanism
  • the sample adding mechanism adds the sample to the reaction container located at the sample addition position of the incubation mechanism.
  • the reagent addition mechanism adds a reagent to the reaction vessel located at the reagent addition site of the incubation mechanism.
  • the incubation mechanism is further provided with a plurality of flow tube positions for carrying the flow tube for containing the waste liquid and the liquid suction head along the annular shape thereof, and the flow tube position is The corresponding reaction cups are adjacent; the transport mechanism also transports the flow tube following the reaction vessel during the stop of the transport reaction vessel.
  • the separation mechanism is for separating the nucleic acid-binding carrier to which the nucleic acid is adsorbed from the reaction solution.
  • the separating mechanism is a recyclable annular structure, and a plurality of reaction cups arranged in at least one row for carrying the reaction container are arranged along the annular interval, and the separating mechanism moves along the cycle
  • the route is distributed with an inlet and outlet position for removing the reaction vessel from the separation mechanism or into the separation mechanism, at least one liquid absorption position, and at least one liquid injection position.
  • the separation mechanism performs the operation stop period according to the preset rotation, and the transport mechanism picks up the reaction vessel that completes the incubation from the incubation mechanism to the entry and exit position of the separation mechanism, or picks up the separated reaction container located at the entry and exit position of the separation mechanism to elute. mechanism.
  • the liquid suction mechanism is configured to perform an aspiration operation at a liquid absorption position of the separation mechanism, and the liquid injection mechanism includes a cleaning liquid injection mechanism for performing a liquid injection operation at the liquid injection position; and the liquid absorption mechanism during the separation of the separation mechanism for performing the operation And the liquid injection mechanism respectively perform a predetermined operation to the reaction container stopped at the liquid suction position and the liquid injection position.
  • the separation mechanism is further provided with a plurality of flow tube positions for carrying the flow tube for containing the waste liquid and the liquid suction head along the annular shape thereof, and the flow tube position is The corresponding reaction cups are adjacent; the transport mechanism also transports the flow tube following the reaction vessel during the stop of the transport reaction vessel.
  • the inside or the outside of the separation mechanism further includes an adsorption mechanism that provides a desired adsorption force for the reaction vessel located at a predetermined position on the separation mechanism.
  • the elution mechanism is used to form an elution product by adding an eluent, which is a recyclable annular structure, and a plurality of reaction cups arranged in at least one column for carrying the reaction vessel are arranged along the annular interval, and eluted
  • the mechanism is distributed along the way of its cyclic movement with a mixed hook, a loading position for placing the reaction container in the elution mechanism, and an eluent addition position.
  • the nucleic acid extraction device further includes a nucleic acid mixing device.
  • the liquid injection mechanism includes an eluent adding mechanism, and the elution mechanism is cyclically advanced according to a preset rotation step and a rotation direction, and the transfer mechanism is located at a mixing hook of the elution mechanism during the stop of the elution mechanism for performing the operation.
  • the reaction container picks up the nucleic acid mixer or picks up the completed reaction container in the nucleic acid mixing device to the mixing hook, and the eluent adding mechanism adds the reaction container to the eluent addition position at the elution mechanism. Eluent.
  • Embodiment 2 will be described in detail below in conjunction with the specific structure of the nucleic acid extraction apparatus of one example.
  • the nucleic acid extraction device includes a working platform on which a plurality of functional areas are arranged, including a consumable area 1, a sample area 3, a reagent area, a nucleic acid storage area 6a, a waste collection area 11a, and the like, and in the work A transfer mechanism, an incubation mechanism, a separation mechanism 12, and an elution mechanism are also installed on the platform.
  • the consumable area 1 is provided with consumables required for the nucleic acid extraction test process, including a reaction vessel such as a reaction cup 18a, a flow tube 18b for use with the reaction cup 18a, and a liquid suction head 18c.
  • the sample area 3 is placed in the sample to be tested.
  • the reagent zone is placed in the kit 5 required for the experiment, and the kit 5 carries all the reagents (such as magnetic bead reagents, eluents, etc.) required for a test item and corresponding Reagent suction head.
  • the extracted nucleic acid is placed in the nucleic acid storage area 6a.
  • the waste recovery area 11a collects the waste liquid generated during the nucleic acid extraction process and the used liquid suction head.
  • a sample loading module 2b is provided in Fig. 1 for taking a sample from the sample area 3 and dispensing it into the reaction cup 18a.
  • a consumable grip cup 2a and a consumable holding arm (not shown), a consumable robot can be provided.
  • reagent loading module 4 for taking a reagent from the reagent cartridge 5 of the reagent zone and dispensing it into the reaction cup 18a, which includes a reagent holding arm (not shown), and the reagent holding arm is sucked by the reagent The liquid head sucks the reagent from the reagent cartridge 5 and dispenses it into the reaction cup 18a.
  • the incubation mechanism performs an incubation operation on the reaction cup 18a after loading the sample and the reagent, and moves the reaction cup 18a to a corresponding position in the separation mechanism after the mixing is completed.
  • an incubation gripper 14, an incubator 13 and an incubator 15 can be provided at this time. Incubating the robot 14 allows the cuvette 18a to be grasped from the incubation tray 13 to the incubator 15 or the separation mechanism, or the cuvette 18a is grasped from the incubation mixer 15 to the incubation tray 13.
  • the incubation tray 13 holds the reaction cup 18a and the flow tube 18b fed by the hand grip 2a and realizes the incubation of the liquid in the reaction cup 18a; the incubation hook 15 is used to incubate and mix the liquid in the reaction cup 18a. .
  • a magnetic separation device is used to remove interfering substances other than nucleic acids in the reaction vessel.
  • the separation mechanism is a circular separation disk.
  • the magnetic separation device includes a separation disc 121, an adsorption structure 122, a liquid absorbing member 16 (corresponding to 16a to 16d in Fig. 1), a liquid injection member 17 (corresponding to 17a to 17b in Fig. 1), and a moving member. (not shown).
  • the separation disc 12 is a recyclable annular structure, and a plurality of reaction cups 124 for carrying the reaction vessel arranged in at least one column are arranged along the annular space thereof, and for carrying and reacting
  • the flow tube position 125 of the flow tube used in the container is adjacent to the corresponding reaction cup position 124, and the recyclable annular structure is distributed along the way of the cyclic movement thereof with a plurality of liquid absorption positions and at least one note Liquid position.
  • Adsorption structure in this embodiment 122 is annular and disposed on the outer ring of the separation disc. In other embodiments, the adsorption structure 122 may also be disposed on the inner ring of the separation disc.
  • the adsorption structure 122 provides the desired adsorption force to the nucleic acid-binding carrier in the reaction vessel on the separation disk so that the nucleic acid-binding carrier in the reaction vessel accumulates under the action of the adsorption force to the side of the reaction vessel near the adsorption structure.
  • the liquid absorbing member 16 is for performing a liquid absorbing operation at the liquid suction position.
  • the liquid injection member 17 is for performing a liquid injection operation at the liquid injection position.
  • the moving member is used to drive the separation disc 121 and the adsorption structure 122 to rotate or stop.
  • the adsorption structure 122 is provided with a plurality of adsorptive members 123 (such as magnets) that can adsorb the extract-binding carrier along the ring shape, and at least one vacancy position without the adsorptive component is disposed on the adsorption structure 122 (not shown) ).
  • adsorptive members 123 such as magnets
  • at least one vacancy position without the adsorptive component is disposed on the adsorption structure 122 (not shown) ).
  • Different operations have different requirements for the adsorption of nucleic acid-binding carriers. Some operations (or the concept of time period) require adsorption, while others do not require adsorption. Therefore, during the rotation or stop of the reaction vessel, the vacancy position of the moving mechanism driving the adsorption mechanism without adsorption force moves without providing an adsorption force position to the extract binding carrier.
  • the separation disc 121 and the adsorption structure 122 can be independently rotated and stopped under the driving of the moving part, so that the vacancy position 1 12 of the adsorption mechanism 11 follows the reaction cup position of the reaction container where the adsorption force is not required, so that During this period, the nucleic acid-binding carrier in the reaction vessel is not subjected to adsorption force, and the nucleic acid-binding carrier is suspended in the solution, which is advantageous for binding more extracts and cleaning impurities on the extract-binding carrier.
  • the vacancy of the moving mechanism driving the adsorption mechanism follows the reaction cup of the reaction vessel to move synchronously.
  • the extract-binding carrier in the reaction vessel is not subjected to adsorption force during the mixing stage after the addition of the cleaning solution.
  • the separating mechanism carries a reaction cup 18a requiring magnetic separation, and a flow tube 18b for use therewith.
  • the flow tube 18b functions to carry the liquid suction head 18c and store waste liquid;
  • a liquid absorbing member 16 and a liquid injection member 17 are disposed above the trajectory of the reaction cup 18a, wherein the liquid absorbing member 16 is arranged in a total of four (16a to 16d), and the liquid injection member 17 is arranged in two (17a to 17b), and the liquid absorbing member 16 is required to load the liquid suction head to suck the liquid in the reaction cup 18a;
  • a magnetic field ring (ie, adsorption structure) 122 which is concentric with the magnetic separation disk 121, is disposed outside the magnetic separation disk 121, and the magnetic field ring 122 is fixed.
  • a magnet 123 is attached for adsorbing the magnetic beads in the cuvette 18a.
  • the magnetic separation disk 121 is arranged in a total of 36 positions for carrying the reaction cup and the flow tube, respectively, wherein the reaction cup and the flow tube are spaced into the magnetic separation disk 121.
  • the reaction cup and the flow tube are instrumented (incubating the cup hand) 14) placing the magnetic separation disk 121 from the position of the 36th position on the magnetic separation disk 121, and then moving forward with the magnetic separation disk 121, in which the position of the outer magnetic field ring corresponding to the reaction cup has a magnetic field, so that The magnetic bead cup is adsorbed to the side of the reaction cup; when the flow tube rotates to the position of the first stage of the liquid absorption mechanism at the position 9 of the magnetic separation disk, the liquid suction mechanism moves downward in the loading flow tube The liquid suction head is then lifted up; thereafter, the magnetic separation disk is retracted to a position such that the reaction cup just enters the position 9 on the magnetic separation disk, and the liquid suction mechanism descends to
  • the design of the flow tube can be made to keep the two positions consistent, and no magnetic is needed.
  • the step of separating the movement of the disk So far, the first-stage aspiration movement of the magnetic separation is completed.
  • the magnetic separation disk and the magnetic field ring of the outer ring thereof are kept in synchronization or stopped, so that the reaction cup is always in the magnetic field adsorption state.
  • the magnetic separation disc continues to advance to three positions, so that the reaction cup enters the 11th position on the magnetic separation disc, that is, below the liquid injection mechanism, and the magnetic field ring occurs during the advancement of the magnetic separation disk.
  • the relative motion makes the part of the magnetic field ring without the magnetic field corresponding to the reaction cup.
  • the liquid injection mechanism injects the cleaning liquid into the reaction cup without the magnetic field adsorption, and then the magnetic separation plate retreats back to the three positions so that the flow tube returns to the first In the first-stage aspiration position, the liquid suction mechanism descends to load the liquid suction head, and then the magnetic separation disk continues to retreat to a position such that the reaction cup is located below the first-stage liquid absorption position, and the liquid suction mechanism drops the cleaning liquid and the magnetic beads in the reaction cup.
  • the magnetic separation disc is further advanced to a position, so that the flow tube is located under the liquid suction mechanism to unload the liquid suction head, and the magnetic separation first-stage liquid injection and the mixing hook operation are completed, and the magnetic separation is performed in the process.
  • the disk and the magnetic field ring are kept in synchronous motion and stopped, so the reaction cup is always in a state of no magnetic field adsorption, and the magnetic beads are resuspended in the cleaning liquid.
  • the magnetic field ring is re-rotated relative to the magnetic separation disc so that the reaction cup is in a magnetic field, and the magnetic field adsorption of the next step is continued.
  • the second-order magnetic separation and liquid-filling action are repeated with the above process, and then the third stage only performs the liquid absorption action, and does not perform the liquid injection action, sucking the liquid in the reaction cup, the fourth order is the third
  • the steps are repeated, and only the liquid is absorbed by the liquid to absorb the residual liquid at the bottom of the cup.
  • reaction cup and the flow tube continue to move back to position 36 with the magnetic separation disc, and the reaction cup and the flow tube are taken away by the instrument for subsequent operations.
  • this process is designed for a specific extraction characteristic.
  • the number of aspirations and injections can be increased or decreased, even in Finally, adding other components of the reaction liquid required for subsequent testing is a possible variant.
  • a nucleic acid loading module 7 is required to extract the eluent from the reagent box 5 of the reagent zone and dispense it into the reaction cup 18a, which may include a nucleic acid holding arm (not shown), nucleic acid
  • the gripping arm realizes an operation of sucking the eluent from the reagent cartridge 5 through the reagent liquid suction head and dispensing it into the reaction container.
  • the elution mechanism performs elution treatment, and elutes the eluted product to be extracted into the elution product storage area. For example, if the eluted product is a nucleic acid, the nucleic acid is extracted into the nucleic acid storage area.
  • an eluting gripper 10, an elution disc 9 and a nucleic acid mixing hook 8 can be provided. Elution of the gripper 10 allows the reaction vessel to be taken from the separation mechanism to the elution tray 9, or the reaction vessel is grasped from the elution tray 9 to the nucleic acid mixing device 8.
  • the elution disk 9 effects elution and incubation of the liquid in the reaction vessel.
  • the nucleic acid mixing device 8 implements a mixing operation of the liquid in the reaction vessel.
  • a process for realizing a nucleic acid extraction by using the nucleic acid extraction device of one embodiment of the present invention including three major steps: a loading incubation step S1, a magnetic separation purification step S3, and Elution step S5.
  • the process for realizing the primary nucleic acid extraction is completed in a reaction cup 18a, which is a disposable use consumable, and a flow tube 18b is used in combination with the reaction cup, and the flow tube is used to carry the magnetic separation process.
  • Sample suction head (Tip) 18c for waste liquid and magnetic separation aspiration.
  • the reaction cup 18a, the flow tube 18b, and the sample tip 18c placed in the flow tube 18b are placed in the consumable loading area 1, and the reaction cup 18a and the flow tube 18b are grasped by the consumable grip cup 2a to the incubation tray. 13;
  • the sample loading module 2b then loads the sample tip 18c, sucks the sample and dispenses it into the reaction cup 18a, and then unloads the sample tip 18c into the flow tube 18b; thereafter, the gripping cup hand 14 is grasped from the incubation disk 13
  • the reaction cup 18a is mixed to the incubation hook 15 to mix.
  • the consumable gripper 2a grabs the next cuvette and its flow tube to the incubator 13 and then performs the same operation as described above.
  • the cuvette 18a is grasped back into the incubation tray and incubated at a constant temperature for a certain period of time.
  • the subsequent cuvette is incubated with the gripping cup 14 and transferred from the incubator 13 to the incubator 15 for mixing.
  • the reaction cup 18a that completes the incubation hook and the corresponding flow tube 18b (the built-in sample tip 18c) are again grasped from the incubation tray 13 by the incubation gripper 14 to the magnetic separation disk 12;
  • a magnetic field is disposed outside the separation disc 12, and the reaction cup 18a performs magnetic adsorption under the action of a magnetic field, and rotates clockwise at a fixed time interval.
  • the liquid suction mechanism 16a loads the sample Tip 18c, and then sucks the waste liquid in the reaction cup 18a; then discharges the waste liquid to the flow Tube 18b, and unloading sample Tip 18c into flow tube 18b, while eluting grip cup 10 grabs the magnetic separation of the cuvette from the magnetic separation disc to the elution tray, or incubating the gripper hand 14 from the incubation tray 13 Grab the next reaction cup to the magnetic separation disc; when the reaction cup 18a that completes the liquid absorption continues to advance under the liquid injection mechanism 17a, the liquid injection mechanism 17a injects the cleaning liquid; then the reaction cup 18a is returned to the lower side of the liquid absorption mechanism 16a, sucking The liquid mechanism 16a loads the sample Tip 18c to perform a suction and discharge hook on the liquid in the cuvette 18a; thus, the first-stage magnetic separation operation is completed.
  • the cuvette 18a and its flow tube 18b continue to advance clockwise, sequentially into the lower portion of the next-stage liquid-absorbent mechanism 16b, below the liquid-filling mechanism 17b, and below the liquid-absorbent mechanism 16b, to complete the second-order magnetic separation operation.
  • the subsequent cuvette performs the first-order magnetic separation operation; thereafter, the cuvette 18a and its flow tube 18b continue to advance to 16c and 16d,
  • the third-order and fourth-order magnetic separation operations, but different from the first two-stage magnetic separation operations, are the second two-stage magnetic separation to perform the aspiration operation without injecting a new cleaning liquid.
  • the reaction cup 18a which has completed the magnetic separation is taken up from the magnetic separation disk 12 by the elution gripper 10 to the elution disk 9 for elution operation, and the corresponding flow tube 18b and the sample Tip 18c are washed.
  • the grasping cup hand 10 is discarded from the throwing cup position 11a after being grasped; the nucleic acid loading module 7 draws the eluent from the reagent box 5 into the reaction cup 18a; then the nucleic acid gripping cup 10 grasps the reaction cup 18a to the nucleic acid mixed After the hooking operation is completed in the hook 8 and then it is taken back into the elution tray 9; the reaction cup 18a is started to be incubated in the elution tray 9 at the same time, and the nucleic acid gripping cup 10 grasps the next reaction cup to the nucleic acid mixed hook.
  • the garbage hook operation is completed in the device 8.
  • the reaction cup 18a is incubated at a constant temperature for a certain period of time, and the elution is completed after the nucleic acid loading module 7 loads the nucleic acid Tip 6b at the nucleic acid Tip cassette 6c, and the eluted product is aspirated from the reaction cup 18a and dispensed into the well on the nucleic acid output plate 6a.
  • the step of extracting the eluted product may be performed under the action of a magnetic field to avoid the absorption of the magnetic beads; thereafter, the nucleic acid Tip 6b is unloaded into the tossing position 11 b to be discarded; and finally the cuvette 18a of the completed test is caught by the nucleic acid.
  • the embodiment of the present invention provides a single-tube based automatic nucleic acid extraction device and a working method thereof, which is performed for each test.
  • each test involves multiple test sessions, including dispensing of the reaction solution, mixing and incubation, magnetic separation, and elution, with a single reaction vessel for each test session.
  • the processing unit for example, when the reaction container A1 completes the operation B1, is flowed to the next operation B2, and the operation B2 is performed, while the next reaction container A2 of the reaction container A1 is flown to the operation B1, and the operation B1 is performed. So on and so forth. Therefore, the single reaction vessel can be used as the processing unit for the flow of the processing unit, and multiple samples are not required to perform the same operation in parallel at the same time, effectively separating the interval between the test and the test, reducing the parallel operation between different tests, and effectively solving the problem. The problem of cross-contamination between tests.

Abstract

一种核酸提取装置及其工作方法，该装置包括：至少一个可循环移动的环形结构（12），其上间隔设置有多个用于承载反应容器（18a）的反应杯位，且沿其循环移动的途径分布有至少一个用于执行吸液操作和至少一个注液操作的操作位；沿环形结构（12）布置的至少一个用于执行吸液操作的吸液机构（16）；沿环形结构（12）布置的至少一个用于执行注液操作的注液机构（17）；用于驱动位于环形结构（12）上的反应容器（18a）沿环形结构（12）的循环移动的途径运动的驱动机构。由于采用可循环移动的环形结构（12）并在其上进行吸液和注液操作，反应杯位为间隔设置，使得在进行核酸提取时可以以单个反应容器（18a）为处理单元一个接一个地处理，由此可减少不同测试之间的并行操作，进而可有效地解决测试之间的交叉污染问题。

Description

核酸提取装置及其工作方法 技术领域
本发明涉及核酸提取技术领域， 具体涉及一种核酸提取装置及其工 作方法。
背景技术
核酸是分子生物学研究的基本对象， 核酸提取步骤是分子诊断中最 为重要、 最基本的一个环节。 从生物样本中提取 DNA或 RNA的方法有 很多， 例如传统的有机溶剂提取方法、 硅胶模柱吸附法、 磁珠分离法和 电荷法等。 其中， 磁珠分离法是目前应用最广、 自动化条件最为成熟的 一种方法， 基本原理是利用具有磁性材料的小微粒表面通过一定的处理 使其可以吸附所需要物质， 然后通过磁铁吸附富集后抛弃废液， 并对富 集的磁珠进行清洗， 进一步清除杂质及其他不需要的物质， 而感兴趣生 物物质因吸附在磁珠上得以保留， 最后在一定条件下将富集在磁珠上的 生物物质释放到所需要的溶液体系中。
现有釆用磁珠分离法的自动化核酸提取设备由全自动酶免系统演变 而来， 一般称为板式方案， 即， 以经典的 96孔板或其变形板（后面统称 96孔板） 为处理单元， 通过并行的多个加样头进行试剂及样本液加样， 然后进行整板的震荡混勾， 完成孵育后再送到磁分离位置进行磁吸附， 并由并行的多个吸液头（Tip )进行吸取废液的操作， 如此重复一定次数 来清洗核酸之外的干扰物质， 然后对完成清洗的 96孔板进行洗脱处理， 得到洗脱产物（即分散在洗脱液中的核酸）， 最后釆用吸液头将洗脱产物 取到一个新的 96孔板中， 以便与 PCR ( polymerase chain reaction, 聚合 酶链反应） 试剂混勾后用于下一环节的核酸检测工作或是执行其它的核 酸检测或处理操作。
由于 PCR检测是以 96孔板为测试单元进行处理， 因此在核酸提取 装置中通常也釆用 96 孔板为测试单元进行每个测试环节的处理。 但在 PCR检测过程中有时会发现交叉感染的现象， 经研究认为与核酸提取装 置中釆用 96孔板为测试单元进行每个测试环节的处理有关 ,这种板式方 案釆用并行方式处理多个样本， 由于孔间距小且孔的深度小， 容易导致 反应液进入周围孔位， 进而形成对周围孔位的污染， 且多头并行的吸液 及排液处理还容易导致交叉污染的风险很高， 此外， 釆用整板震动混匀 也容易造成交叉污染。
由于 PCR技术对核酸进行指数扩增， 会导致测试的灵敏度很高， 且 线性范围很宽， 故而 PCR技术对交叉污染的要求非常高， 而板式方案在 交叉污染的避免方面存在前述的重要缺陷， 这也是制约该方案在临床上 应用的重要原因。 因此亟需一种防止交叉污染的核酸提取装置。
发明内容
依据本发明的第一方面，在一种实施方式中提供一种核酸提取装置， 包括：
至少一个可循环移动的环形结构， 所述环形结构上间隔设置有多个 用于承载反应容器的反应杯位， 所述环形结构沿其循环移动的途径分布 有至少一个用于执行吸液操作和至少一个注液操作的操作位；
沿所述环形结构布置的至少一个用于执行吸液操作的吸液机构； 沿所述环形结构布置的至少一个用于执行注液操作的注液机构； 用于驱动所述环形结构循环移动的驱动机构。
依据本发明的第二方面，在另一种实施方式提供一种核酸提取装置， 包括：
孵育机构， 用于为反应溶液提供进行孵育的场所；
分离机构， 用于将吸附有核酸的核酸结合性载体从反应溶液中分离 出来， 所述分离机构为所述可循环移动的环形结构， 且沿其环形间隔设 置有多个排布成至少一列的用于承载反应容器的反应杯位， 所述分离机 构沿其循环移动的途径分布有用于将反应容器从分离机构取出或放入的 进出位、 至少一个吸液位置和至少一个注液位置；
至少一个吸液机构， 用于在分离机构的吸液位置执行吸液操作； 至少一个注液机构， 用于在分离机构的注液位置执行注液操作； 至少一个用于转运反应容器进出各个机构的转运机构。
依据本申请的第三方面， 在另一种实施方式中提供一种前述核酸提 取装置的工作方法， 包括： 驱动环形结构带动反应容器按照预设的转动 执行操作而停止时， 至少一个吸液机构和至少一个注液机构向位于操作 位的各反应容器执行预定操作， 当反应容器完成预定操作后继续随环形 结构转运到下一操作位。
依据本申请的第四方面， 在另一种实施方式中提供一种前述核酸提 取装置的工作方法， 包括： 驱动所述分离机构按照预设的转动步长和转 动方向循环递进并在停止期间执行预定的操作， 当分离机构为执行操作 而停止时， 所述转运机构将完成孵育的反应容器从孵育机构拾取到分离 机构的进出位， 或拾取出位于分离机构的进出位的已完成分离的反应容 器。
依据本发明的核酸提取装置， 其釆用可循环移动的环形结构并在其 上进行吸液和注液操作， 反应杯位为间隔设置， 使得在进行核酸提取时 可以以单个反应容器为处理单元一个接一个地处理， 由此可以拉开测试 与测试之间的间距， 减少不同测试之间的并行操作， 进而可有效地解决 测试之间的交叉污染问题。
附图说明
图 1是本发明一种实施方式的核酸提取装置的俯视示意图； 图 2是图 1中分离机构的立体结构示意图；
图 3是图 2所示分离机构的工作过程示意图；
图 4是本发明一种实施方式的核酸提取装置的工作流程示意图。 具体实施方式
下面通过具体实施方式结合附图对本发明作进一步详细说明。
[实施例 1]
依据本发明的一种实施方式， 提供一种核酸提取装置， 用于实现核 酸提取过程的完全自动化， 即将一次核酸提取过程中涉及的多个测试环 节 （如包括分注反应液、 混勾及孵育、 磁分离以及洗脱等） 都自动化实 现。 该核酸提取装置包括：
至少一个可循环移动的环形结构， 环形结构上间隔设置有多个用于 承载反应容器的反应杯位， 且环形结构沿其循环移动的途径分布有多个 用于执行吸液操作或注液操作的操作位， 本实施方式中， 环形结构为首 尾相连且可循环运动的结构， 其形状不限， 例如环形结构可以是圓形的 运行轨道， 或者是方形或蛇形的运行轨道；
沿环形结构布置的至少一个用于执行吸液操作的吸液机构； 沿环形结构布置的至少一个用于执行注液操作的注液机构； 用于驱动位于环形结构上的反应容器沿环形结构的循环移动的途径 运动的驱动机构。
对于注液机构， 一种实施例中， 其可以注入的液体包括样本、 试剂、 核酸结合性载体、清洗液和洗脱液，这些注入的液体与对应的操作相关， 例如在进行分离操作中注入的是清洗液。 一种情况下， 在进行孵育操作 时， 核酸结合性载体的注入可以由另外的注液机构进行分注， 该另外的 注液机构不沿环形结构布置， 而是布置在其附近。 另一种情况中， 在进 行洗脱操作时， 洗脱液的注入也可以不由沿环形结构布置的注液机构进 行分注， 而是由另外布置在环形结构附近的其它注液机构予以分注。 此 外， 执行了分离操作之后， 还可以直接注入检测试剂进行检测。
基于本实施方式， 一种实例中， 环形结构仅为一个， 即该环形结构 集孵育操作、 分离操作和洗脱操作为一体。 这些操作与现有核酸提取过 程涉及的操作类似， 例如， 孵育操作包括对反应溶液进行孵育， 分离操 作包括将吸附有核酸的核酸结合性载体从孵育后的反应溶液中分离出 来， 洗脱操作包括向分离后的反应容器中加入洗脱液形成洗脱产物， 洗 脱产物可以不包括核酸结合性载体， 也可以包括核酸结合性载体。
又一种实例中，环形结构为两个， 即第一环形结构和第二环形结构， 第一环形结构用于执行孵育操作、分离操作和洗脱操作中的任两种操作， 而第二环形结构用于执行剩下的一种操作。
另一种实例中， 存在三个环形结构， 其中的一个环形结构用于执行 孵育操作， 另一个环形结构用于执行分离操作， 剩下的一个环形结构用 于执行洗脱操作。
为了进一步解决核酸提取过程中注液针引起的交叉污染问题， 吸液 机构可以使用一次性吸液头进行吸液操作。 容易理解， 核酸提取装置还 需要有至少一个用于转运反应容器进出环形结构的转运机构， 而且核酸 提取中经常需要对反应容器内的反应溶液进行混勾， 因此， 核酸提取装 置还需要包括至少一个混匀器以混匀反应容器内的反应溶液。
更优选地， 核酸提取装置在执行洗脱操作之前， 在转运机构转运反 应容器的停止期间， 转运机构还转运跟随该反应容器的用于承载盛装废 液的流转管， 该流转管还可承载吸液头， 流转管和反应容器配套使用， 进一步避免了由于注液或吸液而导致的交叉污染。 容易理解， 环形结构 上可以设置有流转管位， 该流转管位与反应杯位相邻。
釆用本实施方式的核酸提取装置， 其承载反应容器的反应杯位是间 隔设置在可循环移动的环形结构上， 吸液、 注液等操作均是在该环形结 构上完成。 具体地， 其工作方法是： 驱动环形结构带动反应容器按照预 形结构为执行操作而停止时， 至少一个吸液机构和至少一个注液机构向 位于操作位的反应容器执行预定操作， 当反应容器完成预定操作后继续 随环形结构转运。 可见， 不同于传统的板式结构因为整板为处理单元进 行处理而导致的交叉污染， 本实施方式的核酸提取装置在进行核酸提取 时， 是以单个反应容器为处理单元一个接一个地处理， 这种以单个依次 处理的方案可以拉开测试与测试之间的距离， 减少不同测试之间的并行 操作， 由此可以有效地解决测试之间的交叉污染问题。
[实施例 2]
为更好地理解本发明， 这里以存在三个环形结构的情况为实施例 2 进行描述， 其余数量的环形结构的情况类似。 依据本发明的一种实施方 式， 提供一种核酸提取装置， 包括： 孵育机构、 分离机构、 洗脱机构、 吸液机构、 注液机构和至少一个用于转运反应容器进出各个机构的转运 机构。 应理解， 这里是将核酸提取和检测剥离开， 将核酸提取按孵育、 分离、 洗脱这三个测试环节进行描述， 另一种实例中核酸提取也可以不 进行洗脱， 执行了孵育、 分离操作后， 还可以直接注入检测试剂进行检 测。 形结构， 沿其环形间隔设置有多个排布成至少一列的用于承载反应容器 的反应杯位， 且孵育机构沿其循环移动的途径分布有用于将反应容器从 孵育机构取出进行混勾的混勾位、 用于将反应容器放入孵育机构的放入 位、 样本添加位和试剂添加位。 一种具体实施例中， 核酸提取装置还包 括孵育混匀器， 注液机构包括样本添加机构和试剂添加机构。 孵育机构 按照预设的转动步长和转动方向循环递进， 在孵育机构为执行操作停止 期间， 转运机构将位于孵育机构的混勾位上的反应容器拾取到孵育混匀 器或将孵育混勾器中的完成混勾的反应容器拾取到混勾位， 转运机构将 空的反应容器拾取到孵育机构的放入位， 样本添加机构向位于孵育机构 的样本添加位上的反应容器内添加样本， 试剂添加机构向位于孵育机构 的试剂添加位上的反应容器内添加试剂。 如前一实施例， 为进一步解决 注液针引起的交叉污染问题， 孵育机构沿其环形还设有多个用于承载盛 装废液和吸液头的流转管的流转管位， 流转管位与其对应的反应杯位相 邻； 转运机构在转运反应容器的停止期间， 还转运跟随该反应容器的流 转管。
分离机构用于将吸附有核酸的核酸结合性载体从反应溶液中分离出 来。 分离机构为可循环移动的环形结构， 且沿其环形间隔设置有多个排 布成至少一列的用于承载反应容器的反应杯位， 分离机构沿其循环移动 的途径分布有用于将反应容器从分离机构取出或放入分离机构的进出 位、 至少一个吸液位置和至少一个注液位置。 分离机构按照预设的转动 执行操作停止期间， 转运机构将完成孵育的反应容器从孵育机构拾取到 分离机构的进出位， 或将位于分离机构的进出位的已完成分离的反应容 器拾取到洗脱机构。吸液机构用于在分离机构的吸液位置执行吸液操作， 注液机构包括清洗液注液机构， 用于在注液位置执行注液操作； 在分离 机构为执行操作停止期间， 吸液机构和注液机构分别向停止在吸液位置 和注液位置的反应容器执行预定操作。 如前一实施例， 为进一步解决注 液针引起的交叉污染问题， 分离机构沿其环形还设有多个用于承载盛装 废液和吸液头的流转管的流转管位，流转管位与其对应的反应杯位相邻； 转运机构在转运反应容器的停止期间，还转运跟随该反应容器的流转管。 在釆用例如磁珠分离法进行核酸提取时， 分离机构的内侧或外侧还包括 为位于分离机构上预定位置的反应容器提供需要的吸附力的吸附机构。
洗脱机构用于通过加入洗脱液形成洗脱产物， 为可循环移动的环形 结构， 沿其环形间隔设置有多个排布成至少一列的用于承载反应容器的 反应杯位， 且洗脱机构沿其循环移动的途径分布有混勾位、 用于将反应 容器放入洗脱机构的放入位、 以及洗脱液添加位， 一种实例中， 核酸提 取装置还包括核酸混勾器， 注液机构包括洗脱液添加机构， 洗脱机构按 照预设的转动步长和转动方向循环递进， 在洗脱机构为执行操作停止期 间， 转运机构将位于洗脱机构的混勾位上的反应容器拾取到核酸混匀器 或将核酸混勾器中的完成混勾的反应容器拾取到混勾位， 洗脱液添加机 构向位于洗脱机构的洗脱液添加位上的反应容器内添加洗脱液。
以下结合一种实例中核酸提取装置的具体结构对实施例 2进行详细 的描述。
如图 1所示，核酸提取装置包括工作平台，其上布置了多个功能区， 包括耗材区 1、 样本区 3、 试剂区、 核酸存放区 6a、 废弃物回收区 11a 等， 并且在该工作平台上还安装有转运机构、 孵育机构、 分离机构 12 和洗脱机构。 耗材区 1放置核酸提取测试过程所需的耗材， 包括反应容 器如反应杯 18a、 与反应杯 18a配套使用的流转管 18b及吸液头 18c。 样 本区 3放置实验待检样本。 试剂区放置实验所需的试剂盒 5 , 试剂盒 5 承载一个测试项目所需要的所有试剂 （如磁珠试剂、 洗脱液等） 及相应 的试剂吸液头。 核酸存放区 6a放置提取出的核酸。 废弃物回收区 11a 收集核酸提取过程中产生的废液和已使用过的吸液头。
在进行核酸提取时， 需要实现从样本区和试剂区给反应容器加载样 本和试剂， 加载后将反应容器传送给其它工作机构， 即需要存在提供样 本加样和试剂加样功能的模块。 图 1中提供了样本加样模块 2b , 用于从 样本区 3吸取样本并分注到反应杯 18a, 此时可以设置有耗材抓杯手 2a 和耗材夹持臂（图未示），耗材机械手 2a实现将反应杯 18a和流转管 18b 从耗材区 1移动到其它工作机构的操作， 耗材夹持臂实现从耗材区 1装 载吸液头 18c并从样本区 3给反应容器加载样本、 以及将吸液头 18c卸 载到流转管 18b的操作。 图 1中还提供了试剂加样模块 4用于从试剂区 的试剂盒 5吸取试剂并分注到反应杯 18a,其包括试剂夹持臂（图未示）， 试剂夹持臂实现通过试剂吸液头将试剂从试剂盒 5吸取出并分注到反应 杯 18a的操作。
孵育机构将加载样本和试剂后的反应杯 18a进行孵育操作， 并在混 匀完成后将反应杯 18a移动到分离机构中的对应位置。 具体地， 此时可 以设置有孵育抓杯手 14、 孵育盘 13 和孵育混勾器 15。 孵育机械手 14 实现将反应杯 18a从孵育盘 13抓取到孵育混勾器 15或者分离机构， 或 者实现将反应杯 18a从孵育混匀器 15抓取到孵育盘 13。 孵育盘 13盛装 耗材抓杯手 2a送来的反应杯 18a和流转管 18b并实现对反应杯 18a中的 液体的孵育；孵育混勾器 15实现对反应杯 18a中的液体的孵育和混匀操 作。
本实施例中采用磁分离装置清除反应容器中核酸之外的干扰物质。 为了解决现有共用吸液头引起的交叉污染的问题， 还提出了在分离机构 中釆用一次性吸液头的解决方案， 本实施例中， 分离机构为圓形的分离 盘。 如图 2所示， 磁分离装置包括分离盘 121、 吸附结构 122、 吸液部件 16 (对应图 1中的 16a〜16d )、 注液部件 17 (对应图 1中的 17a~17b )和 移动部件 （图未示）。
一种实施例中，分离盘 1 2为可循环移动的环形结构，且沿其环形间 隔设置有多个排布成至少一列的用于承载反应容器的反应杯位 124、 以 及用于承载与反应容器配套使用的流转管的流转管位 125 ,流转管位 125 与其对应的反应杯位 124相邻， 该可循环移动的环形结构沿其循环移动 的途径分布有多个吸液位置和至少一个注液位置。 该实施例中吸附结构 122为环形， 设置在分离盘的外圈， 在其它实施例中， 吸附结构 122也 可以设置在分离盘的内圈。 吸附结构 122为分离盘上的反应容器内的核 酸结合性载体提供需要的吸附力， 以使反应容器中的核酸结合性载体在 吸附力的作用下聚积到反应容器的靠近吸附结构的一侧。 吸液部件 16 用于在吸液位置执行吸液操作。注液部件 17用于在注液位置执行注液操 作。 移动部件用于驱动分离盘 121和吸附结构 122旋转或停止。
本实施例中， 吸附结构 122沿环形设有多个可吸附提取物结合性载 体的吸附性部件 123 (如磁铁）， 且吸附结构 122上至少设置一个没有吸 附性部件的空缺位（图未示）。不同的操作对核酸结合性载体吸附力的要 求不同， 有些操作 （或者是时间段的概念） 需要有吸附力， 而有些不需 要有吸附力。 因此在反应容器旋转或停止过程中， 移动机构驱动吸附机 构上没有吸附力的空缺位随不需要对提取物结合性载体提供吸附力位置 而移动。 分离盘 121和吸附结构 122可在移动部件的驱动下独立地旋转 和停止，使吸附机构 1 1的空缺位 1 12跟随该不需要吸附力的反应容器所 在的反应杯位同步移动， 从而使得在此期间反应容器中的核酸结合性载 体不受吸附力作用， 核酸结合性载体悬浮在溶液中， 有利于结合更多的 提取物和清洗提取物结合性载体上的杂质。 一种具体实例中， 在反应容 器旋转或停止过程中， 至少在分离盘上的反应容器加入清洗液处于混匀 阶段时， 移动机构驱动吸附机构的空缺位跟随该反应容器的反应杯位同 步移动，使得反应容器中的提取物结合性载体在加入清洗液后的混匀阶 段不受吸附力作用。
结合图 1和图 2所示， 分离机构承载着需要磁分离的反应杯 18a, 以及与之配套使用的流转管 18b , 流转管 18b的作用是用来承载吸液头 18c以及存放废液； 在反应杯 18a运行轨迹上方布置有吸液部件 16以及 注液部件 17 , 其中吸液部件 16共布置 4个（ 16a~16d ), 注液部件 17共 布置 2个（ 17a~17b ),吸液部件 16需要装载吸液头后才可以吸取反应杯 18a中的液体； 在磁分离盘 121 的外侧布置一个可与磁分离盘 121 同心 旋转的磁场环 （即吸附结构） 122 , 磁场环 122 的固定位置安装有磁铁 123用于吸附反应杯 18a中的磁珠。
在一个具体实施例里面， 如图 3所示， 磁分离盘 121上共均排布有 36个位置， 分别用于承载反应杯和流转管， 其中反应杯和流转管间隔进 入磁分离盘 121。 在工作开始时， 反应杯和流转管被仪器 （孵育抓杯手 14 )从磁分离盘 121上第 36号位置一前一后放入磁分离盘 121 , 然后随 着磁分离盘 121旋转递进， 在此过程中反应杯对应的外侧磁场环位置具 有磁场， 使得磁珠杯吸附到反应杯一侧； 当流转管随着磁分离盘旋转到 磁分离盘上第 9号位置即第一阶的吸液机构下方时， 吸液机构向下运动 装载流转管中的吸液头， 然后抬起； 其后磁分离盘向后退一个位置， 使 得反应杯刚好进入磁分离盘上第 9号位置， 吸液机构下降吸取反应杯中 的液体后抬起； 然后磁分离盘继续前进一个位置， 使得流转管位于磁分 离盘上第 9号位置， 然后吸液机构向下运动排出废液并卸载吸液头 （在 此过程中， 由于流转管内排废液位置与卸载吸液头位置并不一致， 因此 需要排完废液后磁分离盘再次运动到卸载吸液头的位置， 当然也可以通 过流转管的设计， 使得两个位置保持一致， 则不需要磁分离盘运动的步 骤）。 至此磁分离第一阶吸液动作完成， 在上述过程中， 磁分离盘和其外 圈的磁场环一致保持同步运动或停止， 因此反应杯一直处于磁场吸附状 态下。 完成第一阶吸液动作后， 磁分离盘继续前进 3个位置 ， 使得反应 杯进入到磁分离盘上第 11号位置即注液机构下方，在磁分离盘前进过程 中 ,磁场环与之发生相对运动使得磁场环上没有磁场的部分对应反应杯 , 此时注液机构在没有磁场吸附作用下向反应杯内注入清洗液， 其后磁分 离盘回退 3个位置使得流转管重新回到第一阶吸液位置， 吸液机构下降 装载吸液头， 然后磁分离盘继续后退一个位置， 使得反应杯位于第一阶 吸液位置下方， 吸液机构下降对反应杯内的清洗液和磁珠进行吸排混匀 后抬起， 然后磁分离盘继续前进一个位置， 使得流转管位于吸液机构下 方卸载吸液头， 至此磁分离第一阶注液及混勾动作完成， 在此过程中磁 分离盘与磁场环一直保持同步运动和停止， 因此反应杯一直处于无磁场 吸附的状态下， 便于磁珠重新悬浮于清洗液中。 完成混勾后磁场环重新 与磁分离盘相对转动使得反应杯处于有磁场的状态下， 继续下一阶的磁 场吸附。 第二阶的磁分离吸液及注液混勾动作与上述过程重复， 然后第 三阶则只进行吸液动作， 不进行注液动作， 吸干反应杯内的液体， 第四 阶同第三阶动作重复， 不注液只吸液进一步吸干杯底的残留液体。至此， 整个磁分离动作完成。 然后反应杯和流转管随着磁分离盘继续运动回到 36号位置， 由仪器取走反应杯和流转管进行后续的操作。 当然这一过程 是针对一个特定的提取特性而设计， 根据提取所需要的洁净程度的不同 以及对残留液体的不同， 可以增加或者减少吸液和注液的次数， 甚至在 最后增加注入后续测试所需要的其他反应液成分，都是可能的变形方案。 洗脱环节中， 需要存在核酸加样模块 7 , 用以从试剂区的试剂盒 5 中吸取洗脱液并分注到反应容杯 18a,其可以包括核酸夹持臂（图未示）， 核酸夹持臂实现通过试剂吸液头将洗脱液从试剂盒 5吸取出并分注到反 应容器的操作。 洗脱机构进行洗脱处理， 并将洗脱得到洗脱产物， 提取 到洗脱产物存放区，例如洗脱产物是核酸， 则将核酸提取到核酸存放区。 此时可以设置有洗脱抓杯手 10、 洗脱盘 9和核酸混勾器 8。 洗脱抓杯手 10实现将反应容器从分离机构抓取到洗脱盘 9 , 或者实现将反应容器从 洗脱盘 9抓取到核酸混勾器 8。 洗脱盘 9实现对反应容器中的液体的洗 脱和孵育操作。 核酸混勾器 8实现对反应容器中的液体的混勾操作。
为便于理解， 参考图 1和图 4 , 下面给出釆用本发明一种实施方式 的核酸提取装置以实现一次核酸提取的过程， 包括三大步骤： 加载孵育 步骤 Sl、 磁分离纯化步骤 S3和洗脱步骤 S5。 其中实现该一次核酸提取 的过程是在一个反应杯 18a内完成， 该反应杯为一次性使用的耗材， 与 反应杯配套使用的还有一个流转管 18b, 流转管用于承载磁分离过程中 产生的废液以及磁分离吸液使用的样本吸液头 （Tip ) 18c。
在加载孵育步骤 S1中：反应杯 18a、流转管 18b以及放在流转管 18b 中的样本 tip 18c放置在耗材加载区 1 , 由耗材抓杯手 2a抓取反应杯 18a 及流转管 18b到孵育盘 13 ; 然后样本加样模块 2b装载样本 tip 18c后吸 取样本并分注到反应杯 18a中 ,随后将样本 tip 18c卸载到流转管 18b中； 其后孵育抓杯手 14从孵育盘 13中抓取反应杯 18a到孵育混勾器 15处进 行混匀。在混勾期间，耗材抓杯手 2a再抓取下一反应杯及其流转管到孵 育盘 13 , 然后执行与上述相同的操作。 完成孵育混勾后， 将反应杯 18a 抓回孵育盘， 在恒定温度下孵育一定时间。 在反应杯 18a开始孵育后， 其后一反应杯被孵育抓杯手 14从孵育盘 13中转移到孵育混勾器 15处进 行混匀。
在磁分离纯化步骤 S3中：完成孵育混勾的反应杯 18a以及与其对应 的流转管 18b (内置样本 tip 18c )再次由孵育抓杯手 14从孵育盘 13中 抓取到磁分离盘 12; 磁分离盘 12外侧布置有磁场， 反应杯 18a在磁场 作用下完成磁吸附作用， 并按照固定的时间间隔向顺时针转动， 当反应 杯 18a及流转管 18b转动到吸液机构 16a的位置处时， 吸液机构 16a装 载样本 Tip 18c , 然后吸取反应杯 18a中的废液； 然后将废液排放到流转 管 18b , 并将样本 Tip 18c卸载到流转管 18b中， 同时洗脱抓杯手 10将 完成磁分离的反应杯从磁分离盘抓取到洗脱盘，或孵育抓杯手 14从孵育 盘 13中抓取下一反应杯到磁分离盘；完成吸液的反应杯 18a继续前进到 达注液机构 17a下方时， 注液机构 17a注入清洗液； 然后反应杯 18a退 回到吸液机构 16a下方， 吸液机构 16a装载样本 Tip 18c对反应杯 18a 内的液体进行吸排混勾； 至此完成第一阶的磁分离操作。 反应杯 18a及 其流转管 18b继续顺时针前进，依次进入到下一阶的吸液机构 16b下方、 注液机构 17b的下方以及吸液机构 16b下方，完成第二阶的磁分离操作。 当反应杯 18a在执行第二阶的磁分离操作时， 其后一个反应杯在执行第 一阶的磁分离操作； 其后反应杯 18a及其流转管 18b继续前进至 16c以 及 16d下方， 执行第三阶及第四阶磁分离操作， 但区别于前两阶磁分离 操作的是后两阶磁分离至进行吸液操作不注入新的清洗液。
在洗脱步骤 S5中： 完成磁分离的反应杯 18a被洗脱抓杯手 10从磁 分离盘 12抓取到洗脱盘 9进行洗脱操作， 相应的流转管 18b 以及样本 Tip 18c则被洗脱抓杯手 10抓取后从抛杯位 11a抛弃； 核酸加样模块 7 从试剂盒 5吸取洗脱液分注到反应杯 18a中；然后核酸抓杯手 10抓取反 应杯 18a到核酸混勾器 8中完成混勾操作后再将其抓回洗脱盘 9中； 反 应杯 18a在洗脱盘 9中开始恒温孵育， 同时，核酸抓杯手 10抓取下一反 应杯到核酸混勾器 8中完成混勾操作。 反应杯 18a恒温孵育一定时间后 完成洗脱；核酸加样模块 7在核酸 Tip盒 6c处装载核酸 Tip 6b后从反应 杯 18a中吸取洗脱产物并将其分注到核酸输出板 6a上的孔位中，其中吸 取洗脱产物的步骤可以在磁场作用下完成， 以避免吸取到磁珠； 其后将 核酸 Tip 6b卸载到抛杯位 11 b中抛弃； 最后完成测试的反应杯 18a被核 酸抓杯手 10抓取后在抛杯位 l ib处抛弃， 至此测试完成。 综上， 依据本发明的实施方式可知， 为了解决板式方案存在的交叉 污染问题， 本发明实施方式提出一种基于单管的全自动核酸提取装置及 其工作方法，该装置进行每次测试时是在一个一次性的反应容器中完成， 每次测试涉及多个测试环节， 包括分注反应液、 混匀及孵育、 磁分离以 及洗脱等， 且每个测试环节中均以单一的反应容器为处理单元， 例如当 反应容器 A1完成操作 B1后， 即被流转到下一操作 B2 , 执行操作 B2 , 同时反应容器 A1的下一个反应容器 A2被流转到操作 B1 ,执行操作 B1 , 依此类推。 由此可以以单一反应容器为处理单元进行流转， 不需要多个 样本同时并行执行相同的操作， 有效地拉开测试和测试之间的间距， 减 少不同测试之间的并行操作， 进而有效地解决了测试之间的交叉污染问 题。
以上应用了具体个例对本发明进行阐述， 只是用于帮助理解本发明 并不用以限制本发明。对于本领域的一般技术人员，依据本发明的思想， 可以对上述具体实施方式进行变化。

Claims

权 利 要 求
1. 一种核酸提取装置， 其特征在于， 包括：
至少一个可循环移动的环形结构， 所述环形结构上间隔设置有多个 用于承载反应容器的反应杯位， 所述环形结构沿其循环移动的途径分布 有至少一个用于执行吸液操作和至少一个注液操作的操作位；
沿所述环形结构布置的至少一个用于执行吸液操作的吸液机构； 沿所述环形结构布置的至少一个用于执行注液操作的注液机构； 用于驱动所述环形结构循环移动的驱动机构。
2. 如权利要求 1所述的核酸提取装置， 其特征在于， 所述环形结构 集孵育操作、 分离操作和洗脱操作为一体， 所述孵育操作包括对反应溶 液进行孵育， 所述分离操作包括将吸附有核酸的核酸结合性载体从孵育 后的反应溶液中分离出来， 所述洗脱操作包括通过向分离后的反应容器 中加入洗脱液形成洗脱产物。
3. 如权利要求 1所述的核酸提取装置， 其特征在于， 所述环形结构 包括第一环形结构和第二环形结构， 第一环形结构用于执行孵育操作、 分离操作和洗脱操作中的任两种操作， 第二环形结构用于执行剩下的一 种操作， 所述孵育操作包括对反应溶液进行孵育， 所述分离操作包括将 吸附有核酸的核酸结合性载体从孵育后的反应溶液中分离出来， 所述洗 脱操作包括通过向分离后的反应容器中加入洗脱液形成洗脱产物。
4. 如权利要求 1所述的核酸提取装置， 其特征在于， 存在三个所述 用于将吸附有核酸的核酸结合性载体从反应溶液中分离出来的分离机 构、 和用于通过加入洗脱液形成洗脱产物的洗脱机构。
5. 如权利要求 4所述的核酸提取装置，其特征在于， 所述分离机构 和孵育机构分别沿其环形还设有多个用于承载盛装废液的流转管的流转 管位 , 所述流转管位与其对应的反应杯位相邻。
6. 如权利要求 1-5任一项所述的核酸提取装置， 其特征在于， 所述 吸液机构使用一次性吸液头进行吸液操作。
7. 如权利要求 1-5任一项所述的核酸提取装置， 其特征在于， 还包 括至少一个用于转运反应容器进出所述环形结构的转运机构。
8. 如权利要求 1-5任一项所述的核酸提取装置， 其特征在于， 还包 括至少一个用于混匀反应容器内的反应溶液的混匀器。
9. 如权利要求 1所述的核酸提取装置， 其特征在于， 所述注液机构 用于向位于所述环形结构上的反应容器至少注入核酸结合性载体和清洗 液。
10. 一种核酸提取装置， 其特征在于， 包括：
孵育机构， 用于为反应溶液提供进行孵育的场所；
分离机构， 用于将吸附有核酸的核酸结合性载体从反应溶液中分离 出来， 所述分离机构为所述可循环移动的环形结构， 且沿其环形间隔设 置有多个排布成至少一列的用于承载反应容器的反应杯位， 所述分离机 构沿其循环移动的途径分布有用于将反应容器从分离机构取出或放入的 进出位、 至少一个吸液位置和至少一个注液位置； 至少一个吸液机构， 用于在分离机构的吸液位置执行吸液操作； 至少一个注液机构， 用于在分离机构的注液位置执行注液操作； 至少一个用于转运反应容器进出各个机构的转运机构。
11. 如权利要求 10所述的核酸提取装置，其特征在于， 孵育机构为 可循环移动的环形结构， 孵育机构沿其环形间隔设置有多个排布成至少 一列的用于承载反应容器的反应杯位。
12.如权利要求 11所述的核酸提取装置， 其特征在于， 所述分离机 构按照预设的转动步长和转动方向循环递进并在停止期间执行预定的操 作， 在分离机构为执行操作停止期间， 所述转运机构将完成孵育的反应 容器从孵育机构拾取到分离机构的进出位， 或拾取出位于分离机构的进 出位的已完成分离的反应容器。
13. 如权利要求 11所述的核酸提取装置，其特征在于， 所述分离机 构和孵育机构分别沿其环形还设有多个用于承载盛装废液的流转管的流 转管位， 所述流转管位与其对应的反应杯位相邻。
14. 如权利要求 13所述的核酸提取装置，其特征在于，在所述转运 机构转运反应容器的停止期间， 所述转运机构还转运跟随该反应容器的 流转管。
15. 如权利要求 10-14任一项所述的核酸提取装置， 其特征在于， 还包括孵育混匀器， 所述注液机构包括样本添加机构和试剂添加机构； 所述孵育机构沿其循环移动的途径分布有用于将反应容器从孵育机 构取出进行混匀的混匀位、 用于将反应容器放入孵育机构的放入位、 样 本添加位和试剂添加位， 孵育机构按照预设的转动步长和转动方向循环 递进， 在孵育机构为执行操作停止期间， 所述转运机构将位于孵育机构 的混勾位上的反应容器拾取到孵育混勾器或将孵育混勾器中的完成混匀 的反应容器拾取到混勾位， 所述转运机构将空的反应容器拾取到孵育机 构的放入位， 样本添加机构向位于孵育机构的样本添加位上的反应容器 内添加样本， 试剂添加机构向位于孵育机构的试剂添加位上的反应容器 内 力口 i式剂。
16. 如权利要求 15所述的核酸提取装置，其特征在于，还包括核酸 混匀器和用于通过加入洗脱液形成洗脱产物的洗脱机构， 所述注液机构 包括洗脱液添加机构， 洗脱机构为可循环移动的环形结构， 洗脱机构沿 其环形间隔设置有多个排布成至少一列的用于承载反应容器的反应杯 位； 所述洗脱机构沿其循环移动的途径分布有混勾位、 用于将反应容器 放入洗脱机构的放入位、 以及洗脱液添加位， 洗脱机构按照预设的转动 步长和转动方向循环递进， 在洗脱机构为执行操作停止期间， 所述转运 机构将位于洗脱机构的混勾位上的反应容器拾取到核酸混勾器或将核酸 混匀器中的完成混匀的反应容器拾取到混匀位， 洗脱液添加机构向位于 洗脱机构的洗脱液添加位上的反应容器内添加洗脱液。
17. 如权利要求 10所述的核酸提取装置，其特征在于，还包括为位 于分离机构上预定位置的反应容器提供需要的吸附力的吸附机构。
18. 一种如权利要求 1-9 任一项所述的核酸提取装置的工作方法， 其特征在于， 驱动环形结构带动反应容器按照预设的转动步长和转动方 向循环递进并在停止期间执行预定的操作， 当环形结构为执行操作而停 止时， 至少一个吸液机构和至少一个注液机构向位于操作位的各反应容 器执行预定操作， 当反应容器完成预定操作后继续随环形结构转运到下 一操作位。
19. 如权利要求 18所述的方法， 其特征在于， 在需要排出废液的反 应容器的反应杯位旁设置用于承载盛装废液的流转管的流转管位， 所述 核酸提取装置在执行洗脱操作之前， 在所述转运机构转运反应容器的停 止期间， 所述转运机构还转运跟随该反应容器的用于承载盛装废液的流 转管。
20. 如权利要求 19所述的方法， 其特征在于， 所述流转管还用于承 载一次性吸液头， 所述吸液机构在吸液操作前先装载一次性吸液头， 通 过一次性吸液头进行吸液操作， 吸液操作完成后再将一次性吸液头卸载 到流转管中。
21. 一种如权利要求 10-17任一项所述的核酸提取装置的工作方法， 其特征在于， 包括： 驱动所述分离机构按照预设的转动步长和转动方向 循环递进并在停止期间执行预定的操作， 当分离机构为执行操作而停止 时， 所述转运机构将完成孵育的反应容器从孵育机构拾取到分离机构的 进出位， 或拾取出位于分离机构的进出位的已完成分离的反应容器。
22. 如权利要求 21所述的方法， 其特征在于， 在分离机构为执行操 作停止期间， 吸液机构和注液机构分别向停止在吸液位置和注液位置的 反应容器执行预定操作。
2 3. 如权利要求 22所述的方法，其特征在于，在所述转运机构转运 反应容器的停止期间， 所述转运机构还转运跟随该反应容器的流转管， 所述流转管用于盛装废液和承载该流转管跟随的反应容器的一次性吸液 头。
24. 如权利要求 23所述的方法，其特征在于还包括： 驱动可循环移 动的环形结构孵育机构按照预设的转动步长和转动方向循环递进， 在孵 育机构为执行操作而停止时， 所述转运机构将位于孵育机构的混勾位上 的反应容器拾取到孵育混匀器或将孵育混匀器中的完成混匀的反应容器 拾取到混勾位，所述转运机构将空的反应容器拾取到孵育机构的放入位， 样本添加机构向位于孵育机构的样本添加位上的反应容器内添加样本 , 试剂添加机构向位于孵育机构的试剂添加位上的反应容器内添加试剂。
25. 如权利要求 24所述的方法，其特征在于，样本添加机构向位于 孵育机构的样本添加位上的反应容器内添加样本的步骤包括：
样本添加机构装载一次性吸液头；
通过一次性吸液头吸取样本并将样本添加到位于孵育机构的样本添 加位上的反应容器内；
样本添加机构将一次性吸液头卸载到跟随该反应容器的流转管内。
26. 如权利要求 23-25 任一项所述的方法， 其特征在于， 在从将反 应容器放入分离盘到该反应容器完成分离的每个工作周期， 包括顺序执 行的至少一次吸注操作和至少一次吸液操作， 所述吸注操作包括：
驱动分离盘带动反应容器及其流转管旋转到吸液位置处；
吸液机构从所述流转管中装载一次性吸液头； 通过一次性吸液头吸取所述反应容器中的废液；
将废液排放到所述流转管中， 并将一次性吸液头卸载到所述流转管 中；
驱动分离盘带动完成吸液的所述反应容器及其流转管前进到注液位 置处；
注液机构向所述反应容器中注入清洗液；
驱动分离盘带动完成注液的所述反应容器及其流转管退回到吸液位 置处；
吸液机构从所述流转管中装载一次性吸液头；
通过一次性吸液头对所述反应容器内的液体进行吸排混匀； 所述吸液操作包括：
驱动分离盘带动反应容器及其流转管前进到吸液位置处；
吸液机构从所述流转管中装载一次性吸液头；
通过一次性吸液头吸取所述反应容器中的废液；
将废液排放到所述流转管中， 并将一次性吸液头卸载到所述流转管 中。
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