WO2023098363A1 - 基于封闭式微流控芯片的核酸提取装置与方法 - Google Patents

基于封闭式微流控芯片的核酸提取装置与方法 Download PDF

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Publication number
WO2023098363A1
WO2023098363A1 PCT/CN2022/128188 CN2022128188W WO2023098363A1 WO 2023098363 A1 WO2023098363 A1 WO 2023098363A1 CN 2022128188 W CN2022128188 W CN 2022128188W WO 2023098363 A1 WO2023098363 A1 WO 2023098363A1
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microfluidic chip
nucleic acid
closed microfluidic
acid extraction
extraction device
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PCT/CN2022/128188
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English (en)
French (fr)
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舒高烽
付满良
吴金龙
阎玉川
张劼
罗七一
常兆华
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上海微创惟微诊断技术有限公司
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Publication of WO2023098363A1 publication Critical patent/WO2023098363A1/zh

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • B01L7/52—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M1/00—Apparatus for enzymology or microbiology
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M1/00—Apparatus for enzymology or microbiology
    • C12M1/36—Apparatus for enzymology or microbiology including condition or time responsive control, e.g. automatically controlled fermentors
    • C12M1/38—Temperature-responsive control
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M1/00—Apparatus for enzymology or microbiology
    • C12M1/42—Apparatus for the treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic waves
    • 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
    • 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
    • C12N15/1013—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 by using magnetic beads
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the present application relates to the field of microfluidic technology, in particular to a nucleic acid extraction device and method based on a closed microfluidic chip.
  • Polymerase Chain Reaction (Polymerase Chain Reaction, PCR) is a molecular biology technique developed in the late 1920s. Through denaturation, annealing and extension, a large number of specific nucleic acid fragments can be replicated. Due to the high sensitivity and specificity of PCR technology, PCR technology is widely used in the field of molecular diagnosis to realize the diagnosis of infectious diseases, early screening of tumors, guidance of medication, and screening of congenital diseases.
  • a nucleic acid extraction device based on a closed microfluidic chip includes magnetic beads and a plurality of connected preset chambers, and the magnetic beads are placed in the preset chambers In the chamber, a phase-change valve for controlling on-off is provided at the connection between the two preset chambers;
  • the nucleic acid extraction device based on a closed microfluidic chip includes:
  • a first temperature control component the first temperature control component has a heating mechanism, and the heating mechanism is used to heat the phase change valve so that the phase change valve is opened to communicate with the two preset chambers;
  • a magnetic attraction the magnetic attraction is within a preset distance from the closed microfluidic chip, and is used to absorb the magnetic beads;
  • a first moving mechanism drives the closed microfluidic chip or the magnetic attraction piece to move, so that the magnetic beads move in the communicated preset chambers.
  • the first temperature control component has a cooling mechanism for cooling the phase change valve so that the phase change valve blocks the communication between the two preset chambers.
  • the nucleic acid extraction device based on the closed microfluidic chip also includes a first support plate for placing the closed microfluidic chip; the first moving mechanism drives the first support plate move.
  • the nucleic acid extraction device based on a closed microfluidic chip further includes a frame and a first guide assembly; the first guide assembly is arranged on the frame, and the first support plate and The first guide assembly is connected;
  • two first pressure plates are provided on the first support plate, and the two first pressure plates respectively press the opposite sides of the closed microfluidic chip;
  • the first support plate is provided with a second pressing plate and a driving mechanism for driving the second pressing plate to move, and the second pressing plate can be set on the closed micro-fluid under the driving of the driving mechanism. on the waterproof and breathable membrane of the control chip and seal the waterproof and breathable membrane.
  • the nucleic acid extraction device based on the closed microfluidic chip further includes a second moving mechanism; the second moving mechanism is connected to the first temperature control assembly and the magnetic attraction member;
  • the heating mechanism includes a first heating plate, and the magnetic attraction is arranged adjacent to the first heating plate.
  • the closed microfluidic chip-based nucleic acid extraction device further includes a mixing mechanism for mixing the liquid in the preset chamber.
  • the mixing mechanism includes a first bracket, an ultrasonic transducer arranged on the first bracket, and a first guide wheel rotatably arranged on the first bracket;
  • the two elastic members are arranged on the frame or the ground, the first support plate is provided with a hollow area that can expose at least one of the preset chambers, and the side of the first support plate is provided with a first avoidance hole;
  • the first moving mechanism drives the first support plate to move above the mixing mechanism, and when the bottom surface of the first support plate collides with the first guide wheel, the ultrasonic transducer and the There is a gap between the closed microfluidic chips placed on the first support plate; when the first guide wheel moves into the first avoidance hole, the ultrasonic transducer and one of the contact with the preset chamber.
  • the number and positions of the first avoidance holes correspond to all the preset chambers one by one;
  • the mixing mechanism further includes a third guide assembly, and the first bracket is connected to the frame or the ground through the third guide assembly.
  • the nucleic acid extraction device based on the closed microfluidic chip further includes a second temperature control component, and the second temperature control component can heat the sample detection chamber of the closed microfluidic chip .
  • the second temperature control assembly includes a second heating plate and a third heating plate arranged at intervals, the temperature heated by the second heating plate is higher than the temperature heated by the third heating plate, so The second heating plate and the third heating plate cycle alternately to heat the sample detection chamber.
  • the second temperature control assembly further includes two semiconductor cooling fins, a radiator and a cooling fan; one of the semiconductor cooling fins is placed between the second heating plate and the radiator, and the other is placed between the second heating plate and the radiator.
  • the semiconductor refrigerating sheet is placed between the third heating plate and the radiator, and the radiator is connected to the cooling fan;
  • the second temperature control assembly is arranged on the frame or the ground through a third elastic member, the second temperature control assembly is provided with a second guide wheel, and the side of the first support plate is provided with a first Two avoidance holes, the first moving mechanism can drive the first support plate to move above the second temperature control assembly; when the bottom surface of the first support plate conflicts with the second guide wheel, There is an interval between the second heating plate and the third heating plate and the closed microfluidic chip placed on the first support plate; when the second guide wheel moves into the first When the second heating plate is out of the hole, the second heating plate or the third heating plate is in contact with the sample detection chamber.
  • the closed microfluidic chip-based nucleic acid extraction device further includes an optical detection module; the optical detection module is used for optical detection of the nucleic acid in the sample detection chamber.
  • the optical detection module includes a fluorescence excitation component, an optical fiber detection component, and a fluorescence reading component; the fluorescence excitation component is used to generate fluorescence, and transmit the generated fluorescence to the optical fiber detection component, the The optical fiber detection component is used to guide the fluorescence into the sample detection chamber, and guide the light reflected by the nucleic acid in the sample detection chamber to the fluorescence reading component.
  • the fluorescence excitation component includes a fluorescence emission end, a dichroic mirror, and a fluorescence emission end; the fluorescence generated by the fluorescence emission end is incident on the dichroic mirror, and passes through the dichroic mirror in turn.
  • the mirror and the fluorescent emitting end emit outwards;
  • the optical fiber detection assembly includes a first transmission fiber, a detection fiber and a second transmission fiber; both ends of the first transmission fiber are respectively connected to the fluorescence emitting end and the detection fiber, and The detection optical fiber and the fluorescence receiving end of the fluorescence reading assembly, the detection optical fiber is facing the sample detection chamber;
  • the fluorescence reading assembly includes a detection camera, an optical filter, and a fluorescence receiving end arranged in sequence, and the fluorescence reflected by the sample in the sample detection chamber is transmitted to the fluorescence receiving end through the detection optical fiber, and the fluorescence receiving end uses The fluorescence is then transmitted to the optical filter, and then incident to the detection camera after being filtered by the optical filter.
  • the optical fiber detection assembly further includes a third moving mechanism and a buffer seat arranged on the frame; the third moving mechanism is connected with the buffer seat, and the third moving mechanism is used to drive The buffer seat moves to the first support plate, and the detection optical fiber is arranged on the buffer seat;
  • the fluorescent reading assembly further includes a mounting base, a fourth moving mechanism disposed on the mounting base, and an array base movably disposed on the mounting base; the fourth moving mechanism is connected to the array base , used to drive the array seat to move; there are at least two fluorescent emitting ends, and at least two optical filters are arranged in one-to-one correspondence with the fluorescent emitting ends; all the optical filters are sequentially arranged on On the array seat, when the fourth moving mechanism drives the array seat to move, the optical filter on the array seat can be sequentially aligned with the fluorescence receiving end.
  • Step S10 when used with a closed microfluidic chip, the magnetic attraction member absorbs the magnetic beads carrying the target object, and the first temperature control component heats the phase change valve of the closed microfluidic chip to open the phase change valve;
  • Step S20 using the first moving mechanism to move the microfluidic chip or the magnetic attraction, so that the magnetic beads carrying the target move from one of the preset chambers to the next preset chamber through the phase change valve in the open state room.
  • the sample liquid is injected into the first preset chamber through the sample inlet, so that the sample liquid is in the preset chamber.
  • the stored reagent reacts, and the target object after reaction is carried by the magnetic beads, and the magnetic beads are adsorbed by the magnetic suction part, and the microfluidic chip or the magnetic suction part is moved by the first moving mechanism, so that the magnetic beads carry the target object and move to the next one.
  • the chamber Preset the chamber, and finally enter the last preset chamber, and get the target in the last preset chamber; then the gas power component acts to make the target enter the sample detection chamber, and then it can be detected in the sample
  • the chamber completes the amplification and detection operations. It can be seen that the extraction operation of the target object is completed in the closed preset chamber, which can reduce the difficulty of the operation, avoid contamination of the sample, and help improve the accuracy of the detection result.
  • FIG. 1 is a schematic structural view of a closed microfluidic chip according to an embodiment of the present application
  • FIG. 2 is a structural diagram of a nucleic acid extraction device based on a closed microfluidic chip according to an embodiment of the present application
  • Fig. 3 is a schematic structural view of one of the side panels of the rack in Fig. 2 hidden;
  • Fig. 4 is a schematic structural view of some parts hidden in Fig. 2;
  • Fig. 5 is a schematic structural diagram of a magnetic attraction part and a first temperature control assembly according to an embodiment of the present application
  • FIG. 6 is a schematic structural view of a closed microfluidic chip disposed on a first support plate according to an embodiment of the present application
  • FIG. 7 is a schematic structural diagram of a fluorescence excitation component according to an embodiment of the present application.
  • FIG. 8 is a schematic structural diagram of an optical fiber detection assembly according to an embodiment of the present application.
  • Fig. 9 is a schematic structural diagram of a fluorescence reading assembly according to an embodiment of the present application.
  • the first temperature control component 21. The first heating plate; 22. The cooling plate; 30. The magnetic attraction; 41. The first moving mechanism; 42. The first support plate; 421. The positioning groove; 422.
  • FIG. 1 shows a schematic structural diagram of a closed microfluidic chip 10 .
  • the closed microfluidic chip 10 includes a chip body 11 , magnetic beads (not shown in the figure) and an aerodynamic component 12 .
  • the chip body 11 is provided with at least two preset chambers 111 arranged sequentially in communication. All adjacent pre-chambers 111 are connected through the first communication channel 112 .
  • wall panels 113 are arranged between all adjacent preset chambers 111, all first communication passages 112 are arranged on the top parts of wall panels 113, and all first communication passages 112 are provided with phase change valves (Fig. not shown).
  • the mouths of all the preset chambers 111 are all blocked by, for example, a sealing film (the sealing film shown in FIG. 1 is hidden, not shown).
  • a reaction reagent or a cleaning solution is provided inside the preset chamber 111 .
  • the chip body 11 is also provided with a sample inlet and an exhaust port. Both the sample inlet and the exhaust port communicate with the first pre-set chamber 111 .
  • the sample liquid is injected into the first preset chamber 111 through the sample inlet.
  • the sample liquid that enters causes the gas in the first preset chamber 111 to be discharged outward through the exhaust port, and the chip body 11
  • a sample detection chamber 114 is also provided on the top, and the sample detection chamber 114 communicates with the preset chamber 111 located at the end. The magnetic beads move in all the preset chambers 111 under the action of the magnetic device.
  • the gas power component 12 communicates with the last pre-set chamber 111 , and pushes the eluent including nucleic acid in the last pre-set chamber 111 to the sample detection chamber by providing air pressure.
  • the gas power component 12 can also communicate with the sample detection chamber 114, and transfer the eluent containing nucleic acid in the last pre-set chamber 111 to the sample detection chamber 114 by providing suction force.
  • an embodiment of the present application provides a nucleic acid extraction device based on a closed microfluidic chip 10.
  • the nucleic acid extraction device based on a closed microfluidic chip 10 includes: a first temperature control component 20, a magnetic attraction Part 30 and the first moving mechanism 41.
  • the first temperature control assembly 20 has a heating mechanism, and the heating mechanism is used to heat the phase change valve so that the phase change valve is opened to communicate with the two preset chambers, that is, the first temperature control assembly 20 can control the phase change of the closed microfluidic chip 10.
  • the heating of the phase change valve causes the phase change valve to open.
  • the magnetic attraction part 30 and the closed microfluidic chip 10 are within a preset distance range, and are used to absorb magnetic beads, and when the phase change valve is in an open state, the magnetic attraction part 30 can absorb and drive the magnetic beads inside the closed microfluidic chip 10. Beads move in all pre-chambers 111 .
  • the magnetic attraction 30 includes but not limited to permanent magnets and electromagnets.
  • the first moving mechanism 41 drives the closed microfluidic chip 10 or the magnetic element 30 to move, so that the magnetic beads move in the connected pre-chamber 111 .
  • the sample liquid is injected into the first preset chamber 111 through the sample inlet, so that the sample liquid is in the preset chamber.
  • the chamber 111 reacts with the stored reagents, carries the reacted target through the magnetic beads, and absorbs the magnetic beads by the magnetic attraction, and moves the microfluidic chip or the magnetic attraction through the first moving mechanism 41, so that the magnetic beads carry the target
  • the object moves to the next preset chamber 111, and finally enters the last preset chamber 111, and the target to be detected is obtained in the last preset chamber 111; then the gas power assembly 12 acts to make the target to be detected
  • the amplification and detection operations can be completed in the sample detection chamber 114. It can be seen that the extraction operation of the target object to be detected is completed in the closed preset chamber 111, which can reduce the difficulty of operation, avoid contamination of the sample, and help improve the accuracy of the detection result.
  • the first temperature control assembly 20 has a cooling mechanism for cooling the phase change valve so that the phase change valve blocks the communication between the two preset chambers.
  • the heating mechanism of the first temperature control component 20 heats the phase-change valve, the phase-change valve changes from a solid state to a liquid state, that is, the phase-change valve is opened, so that the magnetic attraction part 30 can drive the adsorbed magnetic beads through The phase change valve in the liquid state enters into another adjacent preset chamber 111 .
  • the cooling mechanism of the first temperature control assembly 20 is used to lower the temperature, so that the temperature of the phase-change valve can be quickly reduced, so that the phase-change valve can be rapidly transformed from a liquid state to a liquid state. Transform into a solid state, that is, the phase change valve is closed.
  • the phase change valve is closed, the two preset chambers 111 can be better isolated from each other to avoid mutual influence, thereby ensuring the accuracy of nucleic acid extraction.
  • the phase change valve can also be cooled and cooled by natural heat dissipation in the environment where it is located.
  • the nucleic acid extraction device based on the closed microfluidic chip 10 further includes a first support plate 42 for placing the closed microfluidic chip 10 .
  • the closed microfluidic chip 10 is arranged on the first supporting plate 42 , and the first moving mechanism 41 drives the first supporting plate 42 to move. In this way, when the first moving mechanism 41 drives the first support plate 42 to move, it drives the closed microfluidic chip 10 to move accordingly.
  • the nucleic acid extraction device based on the closed microfluidic chip 10 further includes a rack 50 and a first guide assembly 43 .
  • the first guide assembly 43 is disposed on the frame 50 , and the first support plate 42 is connected to the first guide assembly 43 . In this way, when the first moving mechanism 41 drives the first supporting plate 42 to move, under the guidance of the first guiding assembly 43 , the moving effect of the first supporting plate 42 is relatively stable.
  • the first moving mechanism 41 is, for example, disposed on the frame 50 or other positions, which is not limited here, as long as it can drive the first support plate 42 to move.
  • the first moving mechanism 41 includes but is not limited to a screw motor, a belt motor, an air cylinder, and a hydraulic cylinder, which can be set according to actual needs.
  • the first guide assembly 43 includes, but is not limited to, a sliding guide method in which a slide rail cooperates with a slider, and a sliding guide method in which a guide rod and a guide sleeve are used.
  • closed microfluidic chip 10 comprises the first chip body 115 (the left part as shown in Figure 1) and the second chip body 116 (the right side part as shown in Fig. 1) that are connected ). All the preset chambers 111 are sequentially arranged on the first chip body 115 , the sample detection chamber 114 is arranged on the second chip body 116 , and the thickness of the first chip body 115 is greater than that of the second chip body 116 . In addition, in order to perform optical detection on the sample detection chamber 114, the second chip body 116 is a transparent plate.
  • the sample detection chamber 114 is provided with a liquid inlet and an air outlet, and the liquid inlet of the sample detection chamber 114 communicates with the end preset chamber 111.
  • a waterproof gas-permeable membrane is provided at the air outlet end.
  • the gas power assembly 12 acts on the last preset chamber 111, so that the last preset chamber The eluent in 111 is pushed into the sample detection chamber 114, and the gas in the sample detection chamber 114 is discharged outside through the waterproof and gas-permeable membrane.
  • the first support plate 42 is provided with a positioning groove 421 corresponding to the closed microfluidic chip 10 .
  • the position is relatively fixed and the stability is good.
  • two first pressure plates 422 are also provided on the first support plate 42, and the two first pressure plates 422 correspond to the first chip body 115 of the closed microfluidic chip 10 respectively. opposite sides.
  • the two first press plates 422 correspondingly press the opposite sides of the first chip body 115 of the closed microfluidic chip 10, and the closed microfluidic chip 10 can be realized.
  • the flow control chip 10 is firmly arranged on the first support plate 42, so as to ensure the extraction and detection effect of nucleic acid.
  • first pressing plate 422 there may be one first pressing plate 422 or other numbers.
  • the first pressing plate 422 may be pressed against one side of the first chip body 115 .
  • the first pressing plate 422 is not limited to being pressed against the side portion of the first chip body 115, and can also be pressed against other parts of the first chip body 115, as long as it is pressed on the first chip body 115. It does not interfere with the transfer of magnetic beads, ultrasonic mixing, and adjustment of the state of the phase change valve.
  • the first pressing plate 422 is detachably mounted on the first support plate 42 through a fastener 423 , and the pressure on the first chip body 115 can be adjusted by adjusting the tightness of the fastener 423 .
  • the fastener 423 may be, for example, a screw, a bolt, a threaded rod, etc., which is not limited here.
  • the first supporting plate 42 is further provided with a second pressing plate 424 .
  • the second press plate 424 presses the second chip body 116 of the closed microfluidic chip 10, and the pressing area of the second press plate 424 on the second chip body 116 can cover the waterproof and gas-permeable membrane of the closed microfluidic chip 10, and can The sample detection chamber 114 of the closed microfluidic chip 10 is exposed.
  • the second pressing plate 424 is used to press the second chip body 116 of the closed microfluidic chip 10 correspondingly, so that the closed microfluidic chip 10 can be firmly fixed.
  • the second press plate 424 blocks the waterproof and gas-permeable membrane, which can prevent the liquid in the preset chamber 111 from flowing with the liquid in the sample detection chamber 114 to cause pollution. Only under the action of power can the eluent in the pre-set chamber 111 be transferred to the sample detection chamber 114 .
  • the pressing area of the second pressure plate 424 on the second chip body 116 exposes the sample detection chamber 114 of the closed microfluidic chip 10, that is, the second pressure plate 424 is pressed against the second chip body 116 without any interference with the optical path.
  • the blocking can ensure that the optical detection and analysis of the sample detection chamber 114 can be carried out normally.
  • the nucleic acid extraction device based on the closed microfluidic chip 10 also includes a driving mechanism 425, and the driving mechanism 425 is used to drive the second pressing plate 424 to move, and the second pressing plate 424 is driven by the driving mechanism 425.
  • the lower energy is set on the waterproof and gas-permeable membrane of the closed microfluidic chip 10 and seals the waterproof and gas-permeable membrane.
  • the driving mechanism 425 is disposed on the first support plate 42 .
  • the driving mechanism 425 can drive the second platen 424 to move up and down or move horizontally, so as to move away from and close to the closed microfluidic chip 10 .
  • the second pressure plate 424 when the second pressure plate 424 is driven away from the closed microfluidic chip 10 by the driving mechanism 425, the second pressure plate 424 loosens the waterproof and gas-permeable membrane, and the sample detection chamber 114 communicates with the external environment through the waterproof and gas-permeable membrane, and then in the gas Under the power of the power assembly 12, the eluent in the last preset chamber 111 can enter the sample detection chamber 114; and when the eluent completely enters the sample detection chamber 114, the drive mechanism 425 resets, the second pressing plate 424 resets and presses the second chip body 116 of the closed microfluidic chip 10, and the second pressing plate 424 blocks the waterproof and gas-permeable membrane, which can prevent the liquid in the preset chamber 111 from contacting the sample detection chamber.
  • the liquid in 114 flows mutually and causes pollution.
  • the specific design form of the drive mechanism 425 is more, as long as it can drive the second platen 424 up and down, as an example, the drive mechanism 425 includes, for example, a motor (not shown) arranged on the first support plate 42, The eccentric block 4251 arranged on the rotating shaft of the motor, and the frame 4252 arranged on the second pressing plate 424 .
  • the motor shaft drives the eccentric block 4251 to rotate, it can touch the frame 4252 and drive the frame 4252 to move upward, and the frame 4252 correspondingly drives the second pressure plate 424 to move upward to separate from the closed microfluidic chip 10 .
  • the eccentric block 4251 can also rotate to a position separated from the frame 4252 , at this time the second pressing plate 424 resets and presses on the closed microfluidic chip 10 .
  • the first support plate 42 is provided with a first limiting rod 426 and a first elastic member (not shown) disposed on the first limiting rod 426 .
  • the second pressure plate 424 is provided with a first movable hole and is sleeved on the first limiting rod 426 through the first movable hole, and the head of the first limiting rod 426 is away from the second pressure plate 424 through the first elastic member.
  • the surfaces of the first support plate 42 collide.
  • the second pressure plate 424 moves along the first limit rod 426 and compresses the first elastic member; Under the action of the elastic force of the first elastic member, the second pressing plate 424 can be reset and pressed against the second chip body 116 .
  • the number of first limiting rods 426 is not limited to one, but may be two, three or more, and the number of movable holes on the second pressing plate 424 is consistent with the number of first limiting rods 426 .
  • the nucleic acid extraction device based on the closed microfluidic chip 10 further includes a second moving mechanism 61 .
  • the second moving mechanism 61 is connected to the first temperature control assembly 20 and the magnetic attraction member 30 .
  • the second moving mechanism 61 moves the first temperature control assembly 20 or the magnetic attraction 30 up and down, so that the magnetic attraction 30 can be moved To the position where the top surface of the preset chamber 111 is attached to absorb the magnetic beads inside the preset chamber 111, it is also possible to move the first temperature control component 20 to the position where the phase change valve is located, thereby heating the phase change valve or cool down.
  • the first temperature control component 20 includes a first heating plate 21 .
  • the magnetic attraction 30 is arranged adjacent to the first heating plate 21.
  • the first heating plate 21 is synchronously adjacent to the preset chamber 111.
  • the phase change valve is close.
  • the magnetic attraction 30 can make the inside of the preset chamber 111
  • the magnetic beads are attracted to the top surface of the preset chamber 111, and at the same time, because the first heating plate 21 is synchronously approaching the phase change valve adjacent to the preset chamber 111, the phase change valve changes from solid to liquid, so that when the first moving When the mechanism 41 drives the closed microfluidic chip 10 to move, the magnetic beads can pass through the phase change valve and enter the interior of another adjacent preset chamber 111 , which can improve the efficiency of nucleic acid extraction.
  • the first temperature control assembly 20 further includes a cooling plate 22 .
  • the cooling plate 22 , the magnetic element 30 and the first heating plate 21 are arranged in sequence.
  • the cooling plate 22 is synchronously close to the phase change valve between the first preset chamber 111 and the second preset chamber 111, which can reduce the temperature of the phase change valve, so that the phase change valve changes from liquid to solid , that is, the phase change valve is closed, so that the first pre-set chamber 111 and the second pre-set chamber 111 are isolated from each other.
  • the nucleic acid extraction device based on the closed microfluidic chip 10 further includes a frame 50 and a second guide assembly 62 .
  • the second moving mechanism 61 is installed on the frame 50 through the second support plate 63 , and the driving end of the second moving mechanism 61 is respectively connected with the first temperature control component 20 and the magnetic attraction member 30 through the second guiding component 62 .
  • the movement of the first temperature control assembly 20 and the magnetic attraction member 30 is more stable, thereby ensuring the efficiency of nucleic acid extraction.
  • the second moving mechanism 61 is similar to the first moving mechanism 41 and has many design forms, which are not limited here and can be set according to actual needs.
  • the second guide assembly 62 is similar to the first guide assembly 43 and mainly plays a guiding role.
  • the specific structure is not limited and can be set according to actual needs.
  • the second guide assembly 62 includes at least one first guide column 621 disposed on the second support plate 63 , and a first slide plate 622 slidably sleeved on the first guide column 621 .
  • the first sliding plate 622 is provided with a sliding hole and sleeved on the first guide post 621 through the sliding hole.
  • the driving end of the second moving mechanism 61 is connected with the first sliding plate 622 to drive the first sliding plate 622 to move.
  • the first temperature control component 20 and the magnetic element 30 are installed on the first sliding plate 622 .
  • the nucleic acid extraction device based on the closed microfluidic chip 10 further includes a mixing mechanism 70 .
  • the mixing mechanism 70 is used to mix the liquid in the pre-set chamber 111 of the closed microfluidic chip 10 .
  • the mixing mechanism 70 contacts any preset chamber 111 of the closed microfluidic chip 10
  • the liquid in the preset chamber 111 can Mix well to ensure the extraction effect of nucleic acid.
  • the mixing mechanism 70 includes, but is not limited to, an ultrasonic mixing mechanism 70, an oscillating mixing mechanism 70, and the like.
  • the mixing mechanism 70 includes a first bracket 71, an ultrasonic transducer 72 arranged on the first bracket 71, and an ultrasonic transducer 72 arranged on the first bracket rotatably.
  • the first bracket 71 is arranged on the frame 50 or the ground through the second elastic member (not shown in the figure), and the first support plate 42 is provided with a hollowed out area (not shown in the figure) that can expose at least one preset chamber 111 ), the side of the first support plate 42 is provided with a first escape hole 427, and the first moving mechanism 41 can drive the first support plate 42 to move above the mixing mechanism 70.
  • the ultrasonic transducer 72 When the bottom surface of the first support plate 42 was in conflict with the first guide wheel 73, an interval was provided between the ultrasonic transducer 72 and the closed microfluidic chip 10 placed on the first support plate 42; when the first guide wheel 73 When moving into the first escape hole 427 , the ultrasonic transducer 72 is in contact with one of the preset chambers 111 . In this way, the first moving mechanism 41 drives the first support plate 42 to move above the mixing mechanism 70, and when the first guide wheel 73 moves into the first avoidance hole 427, the ultrasonic transducer 72 is in contact with one of them.
  • the preset chamber 111 contacts and mixes the liquid in the preset chamber 111; when the first guide wheel 73 does not move into the first escape hole 427, the first guide wheel 73 and the first support plate
  • the bottom surface of 42 is pressed down by the gravity of the first support plate 42, so that the second elastic member is compressed, and there is a gap between the ultrasonic transducer 72 and the closed microfluidic chip 10 placed on the first support plate 42, That is, the ultrasonic transducer 72 is not in contact with the preset chamber 111 , so the ultrasonic transducer 72 will not transmit ultrasonic energy to the closed microfluidic chip 10 .
  • the number and position of the first escape holes 427 correspond to all the preset chambers 111 of the closed microfluidic chip 10 one by one.
  • the first support plate 42 drives the closed microfluidic chip 10 to move above the mixing mechanism 70
  • the first guide wheel 73 enters one of the first avoidance holes 427
  • the first avoidance hole 427 corresponds to
  • the preset chamber 111 is convenient to be in contact with the ultrasonic transducer 72, and the ultrasonic transducer 72 can realize the mixing action of the preset chamber 111. Therefore, the ultrasonic transducer 72 can be in contact with the bottom surfaces of all the preset chambers 111 , that is, all the preset chambers 111 can be mixed by the ultrasonic transducer 72 according to actual needs.
  • the number of first escape holes 427 may also be less than the number of pre-chambers 111 of the closed microfluidic chip 10 , which is not limited here.
  • first guide wheels 73 are provided on opposite sides of the first bracket 71, and first guide wheels 73 are provided on opposite sides of the first support plate 42.
  • the two first guide wheels 73 of the first bracket 71 can enter into the two first avoidance holes 427 correspondingly and synchronously.
  • the first support plate 42 moves above the mixing mechanism 70, when the two first guide wheels 73 do not move into the two first escape holes 427, the first support plate 42 is synchronized with the two first avoidance holes 427.
  • a guide wheel 73 is in contact with each other, and the movement stability of the first support plate 42 is better.
  • the mixing mechanism 70 further includes a third guide assembly 74 .
  • the first bracket 71 is connected with the frame 50 or the ground through the third guide assembly 74 . In this way, under the guidance of the third guide assembly 74 , the first bracket 71 is raised and lowered in a straight line with better stability.
  • the specific combination form of the third guide assembly 74 is similar to that of the first guide assembly 43 , which is not limited here.
  • the third guide assembly 74 can be provided in one, two, three or other numbers.
  • the second elastic member is, for example, a spring, which is sleeved outside the third guide assembly 74 . One end of the second elastic member is connected to the first bracket 71 , and the other end is connected to the third guide assembly 74 or to the frame 50 .
  • the nucleic acid extraction device based on the closed microfluidic chip 10 further includes a second temperature control component 81 .
  • the second temperature control component 81 can heat the sample detection chamber 114 of the closed microfluidic chip 10 . In this way, when the eluent enters the sample detection chamber 114, the second temperature control component 81 heats the eluent in the sample detection chamber 114 in a cycle of high temperature and low temperature, so as to realize nucleic acid amplification.
  • the second temperature control assembly 81 includes a second heating plate 811 and a third heating plate 812 arranged at intervals.
  • the temperature heated by the second heating plate 811 is higher than the temperature heated by the third heating plate 812 , and the second heating plate 811 and the third heating plate 812 cycle alternately to heat the sample detection chamber 114 .
  • the second heating plate 811 and the third heating plate 812 constitute dual-temperature zone heating, which reduces the time required for the heat source to change temperature, improves the heating and cooling rate of the liquid, and shortens the amplification detection time.
  • the second temperature control assembly 81 further includes two semiconductor cooling fins 813 , a radiator 814 and a cooling fan 815 .
  • One semiconductor cooling chip 813 is placed between the second heating plate 811 and the radiator 814
  • the other semiconductor cooling chip 813 is placed between the third heating plate 812 and the radiator 814 .
  • the radiator 814 is connected with a cooling fan 815 .
  • the second heating plate 811 and the third heating plate 812 can also be heated in other ways, such as heat conduction through electric heating wires, which is not limited here and can be set according to actual needs.
  • the second temperature control assembly 81 is arranged on the frame 50 or the ground through a third elastic member (not shown in the figure), and the second temperature control assembly 81 is set There is a second guide wheel 82 , and a second avoidance hole 428 is provided on the side of the first support plate 42 , and the first moving mechanism 41 can drive the first support plate 42 to move above the second temperature control assembly 81 .
  • the bottom surface of the first support plate 42 is in contact with the second guide wheel 82, there is a gap between the second heating plate 811 and the third heating plate 812 and the closed microfluidic chip 10 placed on the first support plate 42.
  • the second heating plate 811 or the third heating plate 812 is in contact with the sample detection chamber 114 .
  • the first moving mechanism 41 drives the first support plate 42 to move above the second temperature control assembly 81
  • the second guide wheel 82 moves into the second avoidance hole 428
  • the third heating plate 812 is in contact with the sample detection chamber 114, and heats and amplifies the nucleic acid in the sample detection chamber 114
  • the second guide wheel 82 does not move into the second escape hole 428, the second guide wheel 82 is in contact with the bottom surface of the first support plate 42 and is pressed down by the gravity of the first support plate 42, so that the third elastic member is compressed, and the second heating plate 811 and the third heating plate 812 are placed on the first support plate 42.
  • the second temperature control assembly 81 is disposed on the frame 50 through the fourth guide assembly 83 , and under the guidance of the fourth guide assembly 83 , the movement of the second temperature control assembly 81 is more stable.
  • the first support plate 42 drives the closed microfluidic chip 10 to move above the second temperature control assembly 81
  • the second guide wheels 82 sequentially enter the second avoidance holes 428
  • the second heating plate 811 and the third heating plate 812 will be in contact with the sample detection chamber 114 successively, so as to heat the sample detection chamber 114 sequentially.
  • the nucleic acid extraction device based on the closed microfluidic chip 10 further includes an optical detection module 90 .
  • the optical detection module 90 is used for optical detection of the nucleic acid in the sample detection chamber 114 .
  • the optical detection module 90 includes a fluorescence excitation component 91 , an optical fiber detection component 92 and a fluorescence reading component 93 .
  • the fluorescence excitation component 91 is used to generate fluorescence, and emit the generated fluorescence to the optical fiber detection component 92
  • the optical fiber detection component 92 is used to introduce the fluorescence into the nucleic acid in the sample detection chamber 114, and detect the nucleic acid in the sample detection chamber 114 The reflected light is directed to the fluorescent reading assembly 93 .
  • the fluorescence excitation component 91 includes a fluorescence emission end 911 , a dichroic mirror 912 and a fluorescence emission end 913 . Fluorescence generated by the fluorescence emission end 911 is incident on the dichroic mirror 912 , and is emitted outward through the dichroic mirror 912 and the fluorescence emission end 913 in sequence.
  • the fiber detection assembly 92 includes a first transmission fiber (not shown in the figure), a detection fiber 921 and a second transmission fiber (not shown in the figure). Both ends of the first transmission fiber are respectively connected to the fluorescence emission end 913 and the detection fiber 921 , and the two ends of the second transmission fiber are respectively connected to the detection fiber 921 and the fluorescence receiving end 933 of the fluorescence reading assembly 93 , and the detection fiber 921 faces the sample detection chamber 114 .
  • the fluorescence reading assembly 93 includes a detection camera 931 , a filter 932 and a fluorescence receiving end 933 arranged in sequence.
  • the fluorescence reflected by the sample in the sample detection chamber 114 is transmitted to the fluorescence receiving end 933 through the detection optical fiber 921 , and the fluorescence receiving end 933 is used to transmit the fluorescence to the filter 932 , and then enter the detection camera 931 after being filtered by the filter 932 .
  • the optical fiber detection assembly 92 further includes a third moving mechanism 922 and a buffer seat 923 disposed on the frame 50 .
  • the third moving mechanism 922 is connected with the buffer seat 923 , and the third moving mechanism 922 is used to drive the buffer seat 923 to move to the first support plate 42 , and the detection optical fiber 921 is arranged on the buffer seat 923 .
  • the third moving mechanism 922 drives the buffer seat 923 to move, and the buffer seat 923 moves by contacting the first support plate 42
  • the detection optical fiber 921 is facing the sample detection chamber 114 on the closed microfluidic chip 10, so that the fluorescence can be incident on the surface of the nucleic acid sample in the sample detection chamber 114, and receive the light from the surface of the nucleic acid sample. Fluorescence reflected back.
  • the first support plate 42 is provided with a second pressure plate 424, and the buffer seat 923 is positioned after moving downward against the second pressure plate 424, that is, the buffer seat 923 indirectly contacts the first support plate 42 .
  • the third moving mechanism 922 is similar to the first moving mechanism 41 , and its specific structure is not limited, as long as it can drive the buffer seat 923 to move.
  • the third moving mechanism 922 is installed on the frame 50 through the third support plate 925, and the fifth guide assembly 924 is arranged on the third support plate 925, and the fifth guide assembly 924 is connected with the buffer seat 923, so that the third When the moving mechanism 922 drives the buffer seat 923 to move, the fifth guide assembly 924 guides, and the buffer seat 923 moves more smoothly.
  • the fluorescence reading assembly 93 further includes a mounting base 934 , a fourth moving mechanism disposed on the mounting base 934 , and an array base 935 movably disposed on the mounting base 934 .
  • the fourth moving mechanism is connected with the array seat 935 and is used to drive the array seat 935 to move.
  • There are at least two fluorescence emitting ends 911 and at least two optical filters 932 are set in one-to-one correspondence with the fluorescence emitting ends 911 . All the filters 932 are sequentially arranged on the array seat 935 , and when the fourth moving mechanism drives the array seat 935 to move, the filters 932 on the array seat 935 can be aligned with the fluorescence receiving end 933 sequentially.
  • the fluorescent emitting ends 911 are turned on sequentially.
  • the fourth moving mechanism drives the array base 935 to move, so that the filter 932 corresponding to the fluorescent emitting ends 911 moves to the position corresponding to the fluorescent receiving ends 933.
  • the switching detection of multiple optical paths can be realized in a short time, which reduces the detection time and improves the detection speed under the premise of ensuring accuracy.
  • a nucleic acid extraction method based on a closed microfluidic chip 10 using the nucleic acid extraction device based on a closed microfluidic chip 10 in any of the above embodiments, includes the following steps:
  • Step S10 when used in conjunction with the closed microfluidic chip 10, the magnetic attraction member absorbs the magnetic beads carrying the target, and the first temperature control component 20 heats the phase change valve of the closed microfluidic chip 10 to open the phase change valve;
  • Step S20 using the first moving mechanism 41 to move the microfluidic chip or the magnetic attraction, so that the magnetic beads carrying the target move from one of the preset chambers 111 through the open phase change valve to the next preset chamber Room 111.
  • the extraction operation of the target object is completed in the pre-set chamber 111 in a closed state, which can reduce the difficulty of operation, avoid contamination of samples, and help improve the accuracy of detection results. Spend.
  • the nucleic acid extraction method based on the closed microfluidic chip 10 also includes steps:
  • Step S30 when the magnetic beads carrying the target move from one of the preset chambers 111 through the phase change valve in the open state to the next preset chamber 111, the first temperature control assembly 20 is used to control the phase change valve in the open state.
  • the temperature of the phase change valve is lowered so that the phase change valve changes from a liquid state to a solid state and closes.
  • Step S40 when the phase change valve is closed, drive the magnetic attraction away from the closed microfluidic chip 10, and move the closed microfluidic chip 10 or the mixing mechanism 70, so that the mixing mechanism 70 contacts the preset chamber with the magnetic beads 111 , mixing the liquid in the preset chamber 111 by the mixing mechanism 70 .
  • Step S50 repeating the above step S10 to step S40 until the magnetic beads carry the target into the last pre-set chamber 111 .
  • Step S60 under the power of the gas power assembly 12, push the eluent in the last preset chamber 111 into the sample detection chamber 114;
  • Step S70 move the closed microfluidic chip 10 or the second temperature control component 81, so that the second temperature control component 81 contacts the sample detection chamber 114; the second temperature control component 81 provides two different preset temperatures, with two different The preset temperature works alternately and transfers heat to the sample detection chamber 114 .
  • the two different preset temperatures are high temperature and low temperature, respectively, and the specific size can be set according to the actual situation.
  • the second temperature control component 81 alternately contacts the sample detection chamber 114 with two different preset temperatures, so that the sample can be detected. Nucleic acid within chamber 114 is amplified.
  • Step S80 after heating the inside of the sample detection chamber 114 by the second temperature control component 81 for a preset time, move the closed microfluidic chip 10 or the optical detection module 90 so that the optical detection module 90 can be connected with the sample detection chamber 114 alignment, and perform optical detection on the nucleic acid in the sample detection chamber 114 .
  • first and second are used for descriptive purposes only, and cannot be interpreted as indicating or implying relative importance or implicitly specifying the quantity of indicated technical features.
  • the features defined as “first” and “second” may explicitly or implicitly include at least one of these features.
  • “plurality” means at least two, such as two, three, etc., unless otherwise specifically defined.
  • a first feature being "on” or “under” a second feature may mean that the first and second features are in direct contact, or that the first and second features are indirect through an intermediary. touch.
  • “above”, “above” and “above” the first feature on the second feature may mean that the first feature is directly above or obliquely above the second feature, or simply means that the first feature is higher in level than the second feature.
  • “Below”, “beneath” and “beneath” the first feature may mean that the first feature is directly below or obliquely below the second feature, or simply means that the first feature is less horizontally than the second feature.

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Abstract

一种基于封闭式微流控芯片的核酸提取装置与方法。配合封闭式微流控芯片(10)使用时，将样本液通过进样口注入到位于首位的预置腔室(111)内，使得样本液在预置腔室(111)内与储存的试剂发生反应，通过磁珠携带反应后的目标物，并借用磁吸件(30)吸附磁珠，通过第一移动机构(41)移动微流控芯片(10)或磁吸件(30)，使得磁珠携带目标物移动到下一个预置腔室(111)，并最终进入到末尾的预置腔室(111)，在末尾的预置腔室(111)得到目标物；然后通过气体动力组件(12)进行动作，使得目标物进入到样品检测腔室(114)内，便可以在样品检测腔室(114)完成扩增与检测操作。如此可见，目标物的提取操作，是位于封闭状态的预置腔室(111)中完成，能够降低操作难度，能避免污染样本，有利于提高检测结果的准确度。

Description

基于封闭式微流控芯片的核酸提取装置与方法
相关申请的交叉引用
本公开要求于2021年12月2日提交中国专利局、申请号为2021114627371、名称为“基于封闭式微流控芯片的核酸提取装置与方法”的中国专利的优先权，所述专利申请的全部内容通过引用结合在本公开中。
技术领域
本申请涉及微流控技术领域，特别是涉及一种基于封闭式微流控芯片的核酸提取装置与方法。
背景技术
聚合酶链式反应(Polymerase Chain Reaction,PCR)是20年代末期发展的分子生物学技术，通过变性、退火和延伸，实现对特定核酸片段的大量复制。由于PCR技术的高灵敏度和特异性，PCR技术广泛应用于分子诊断领域实现对传染病诊断、肿瘤早筛、指导用药以及先天疾病筛查等方面。
传统的PCR技术的应用场景须在专业的分子实验室中进行，对整个过程有着严格的控制，必须有独立的样本制备间、试剂准备间、分析实验室等。用户需使用大型工作站或者提取仪对样本的核酸进行提取，后将提取完毕的核酸片段转移到PCR管内，再加载到PCR仪器上进行扩增分析检测。此类操作不仅需要专业人员和在专业场地进行，而且在操作过程中存在污染样本的可能，进而导致错误的检测结果。
发明内容
基于此，有必要克服现有技术的缺陷，提供一种基于封闭式微流控芯片的核酸提取装置与方法，它能够降低操作难度，能避免污染样本，有利于提高检测结果的准确度。
其技术方案如下：一种基于封闭式微流控芯片的核酸提取装置，所述封闭式微流控芯片包括磁珠以及多个相连通的预置腔室，所述磁珠置于所述预置腔室中，两个预置腔室的相连通处设有控制通断的相变阀；所述基于封闭式微流控芯片的核酸提取装置包括：
第一温控组件，所述第一温控组件具有加热机构，所述加热机构用于对所述相变阀加热使得所述相变阀开启以连通所述两个预置腔室；
磁吸件，所述磁吸件与所述封闭式微流控芯片处于预设距离范围内，用于吸附所述磁珠；
第一移动机构，所述第一移动机构驱动所述封闭式微流控芯片或所述磁吸件移动，使所述磁珠在相通的预置腔室中移动。
在其中一个实施例中，所述第一温控组件具有对所述相变阀降温处理使得所述相变阀阻断所述两个预置腔室连通的降温机构。
在其中一个实施例中，所述基于封闭式微流控芯片的核酸提取装置还包括用于放置所述封闭式微流控芯片的第一支撑板；所述第一移动机构驱动所述第一支撑板移动。
在其中一个实施例中，所述基于封闭式微流控芯片的核酸提取装置还包括机架与第一导向组件；所述第一导向组件设置于所述机架上，所述第一支撑板与所述第一导向组件相连；
和/或，所述第一支撑板上设有两个第一压板，两个第一压板分别对应压住所述封闭式微流控芯片相对两侧；
和/或，所述第一支撑板上设有第二压板以及用于驱动第二压板运动的驱动机构，所述第二压板在所述驱动机构的驱动下能压设在所述封闭式微流控芯片的防水透气膜上并密闭所述防水透气膜。
在其中一个实施例中，所述基于封闭式微流控芯片的核酸提取装置还包括第二移动机构；所述第二移动机构与所述第一温控组件、所述磁吸件均相连；
和/或，所述加热机构包括第一加热板，所述磁吸件与所述第一加热板相邻设置。
在其中一个实施例中，所述基于封闭式微流控芯片的核酸提取装置还包括用于将所述预置腔室内的液体混匀的混匀机构。
在其中一个实施例中，所述混匀机构包括第一支架、设置于第一支架上的超声换能器、转动地设置于第一支架上的第一导向轮；所述第一支架通过第二弹性件设置于机架或地面上，所述第一支撑板设有能露出至少一个所述预置腔室的镂空区，所述第一支撑板的侧部设有第一避让孔；所述第一移动机构驱动所述 第一支撑板移动到所述混匀机构的上方，当所述第一支撑板的底面与所述第一导向轮相抵触时，所述超声换能器与所述第一支撑板上放置的所述封闭式微流控芯片之间设有间隔；当所述第一导向轮移动进入到所述第一避让孔中时，所述超声换能器与其中一个所述预置腔室相接触。
在其中一个实施例中，所述第一避让孔的数量和位置与所有所述预置腔室一一对应；
和/或，所述混匀机构还包括第三导向组件，所述第一支架通过所述第三导向组件与所述机架或所述地面相连。
在其中一个实施例中，所述基于封闭式微流控芯片的核酸提取装置还包括第二温控组件，所述第二温控组件能够对所述封闭式微流控芯片的样品检测腔室进行加热。
在其中一个实施例中，所述第二温控组件包括间隔设置的第二加热板与第三加热板，所述第二加热板加热的温度高于所述第三加热板加热的温度，所述第二加热板与所述第三加热板循环交替给所述样品检测腔室加热。
在其中一个实施例中，所述第二温控组件还包括两个半导体制冷片、散热器与散热风扇；其中一半导体制冷片置于所述第二加热板和所述散热器间，另一半导体制冷片置于第三加热板和所述散热器间，所述散热器与所述散热风扇相连；
和/或，所述第二温控组件通过第三弹性件设置于机架或地面上，所述第二温控组件设有第二导向轮，所述第一支撑板的侧部设有第二避让孔，所述第一移动机构能驱动所述第一支撑板移动到所述第二温控组件的上方；当所述第一支撑板的底面与所述第二导向轮相抵触时，所述第二加热板、所述第三加热板均与所述第一支撑板上放置的所述封闭式微流控芯片之间设有间隔；当所述第二导向轮移动进入到所述第二避让孔中时，所述第二加热板或所述第三加热板与所述样品检测腔室相接触。
在其中一个实施例中，所述基于封闭式微流控芯片的核酸提取装置还包括光学检测模块；所述光学检测模块用于对样品检测腔室内的核酸进行光学检测。
在其中一个实施例中，所述光学检测模块包括荧光激发组件、光纤检测组件与荧光读数组件；所述荧光激发组件用于产生荧光，并将产生的荧光发射到所述光纤检测组件，所述光纤检测组件用于将荧光导入到样品检测腔室，并将经所述样品检测腔室中的核酸反射的光线导入给所述荧光读数组件。
在其中一个实施例中，所述荧光激发组件包括荧光发射端、二向色镜与荧光出射端；所述荧光发射端产生的荧光入射到所述二向色镜，依次经过所述二向色镜与所述荧光出射端向外射出；
所述光纤检测组件包括第一传输光纤、检测光纤与第二传输光纤；所述第一传输光纤两端分别连接所述荧光出射端、所述检测光纤，所述第二传输光纤两端分别连接所述检测光纤与所述荧光读数组件的荧光接收端，所述检测光纤对着所述样品检测腔室；
所述荧光读数组件包括依次设置的检测相机、滤光片与荧光接收端，所述样品检测腔室的样品反射的荧光经过所述检测光纤传输给所述荧光接收端，所述荧光接收端用于将荧光传输给所述滤光片，经所述滤光片过滤后入射到所述检测相机。
在其中一个实施例中，所述光纤检测组件还包括设置于机架上的第三移动机构与缓冲座；所述第三移动机构与所述缓冲座相连，所述第三移动机构用于驱动所述缓冲座移动到所述第一支撑板上，所述检测光纤设置于所述缓冲座上；
和/或，所述荧光读数组件还包括安装座、设置于安装座上的第四移动机构、以及可移动地设置于安装座上的阵列座；所述第四移动机构与所述阵列座相连，用于驱动阵列座移动；所述荧光发射端为至少两个，所述滤光片为至少两个并与所述荧光发射端一一对应设置；所有所述滤光片均依次地设置于所述阵列座上，所述第四移动机构驱动所述阵列座移动时，能使得所述阵列座上的所述滤光片依次与所述荧光接收端对位。
一种基于封闭式微流控芯片的核酸提取方法，采用了所述的基于封闭式微流控芯片的核酸提取装置，包括如下步骤：
步骤S10、配合封闭式微流控芯片使用时，磁吸件吸附携带目标物的磁珠，第一温控组件对封闭式微流控芯片的相变阀加热使得所述相变阀开启；
步骤S20、通过第一移动机构移动微流控芯片或磁吸件，使得携带目标物的磁珠从其中一个所述预置腔室穿过处于开启状态的相变阀移动到下一个预置腔室。
上述的基于封闭式微流控芯片的核酸提取装置与方法，配合封闭式微流控芯片使用时，将样本液通过进样口注入到位于首位的预置腔室内，使得样本液在预置腔室内与储存的试剂发生反应，通过磁珠携带反应后的目标物，并借用磁吸件吸附磁珠，通过第一移动机构移动微流控芯片或磁吸件，使得磁珠携带目标 物移动到下一个预置腔室，并最终进入到末尾的预置腔室，在末尾的预置腔室得到目标物；然后通过气体动力组件进行动作，使得目标物进入到样品检测腔室内，便可以在样品检测腔室完成扩增与检测操作。如此可见，目标物的提取操作，是位于封闭状态的预置腔室中完成，能够降低操作难度，能避免污染样本，有利于提高检测结果的准确度。
附图说明
构成本申请的一部分的附图用来提供对本申请的进一步理解，本申请的示意性实施例及其说明用于解释本申请，并不构成对本申请的不当限定。
为了更清楚地说明本申请实施例中的技术方案，下面将对实施例描述中所需要使用的附图作简单地介绍，显而易见地，下面描述中的附图仅仅是本申请的一些实施例，对于本领域普通技术人员来讲，在不付出创造性劳动的前提下，还可以根据这些附图获得其他的附图。
图1为本申请一实施例的封闭式微流控芯片的结构示意图；
图2为本申请一实施例的基于封闭式微流控芯片的核酸提取装置的结构图；
图3为图2中的机架的其中一侧板隐藏后的结构示意图；
图4为图2中的部分部件隐藏后的结构示意图；
图5为本申请一实施例的磁吸件与第一温控组件的结构示意图；
图6为本申请一实施例的封闭式微流控芯片设置于第一支撑板上的结构示意图；
图7为本申请一实施例的荧光激发组件的结构示意图；
图8为本申请一实施例的光纤检测组件的结构示意图；
图9为本申请一实施例的荧光读数组件的结构示意图。
10、封闭式微流控芯片；11、芯片本体；111、预置腔室；112、第一连通通道；113、墙板；114、样品检测腔室；115、第一芯片体；116、第二芯片体；12、气体动力组件；
20、第一温控组件；21、第一加热板；22、降温板；30、磁吸件；41、第一移动机构；42、第一支撑板；421、定位槽；422、第一压板；423、紧固件；424、第二压板；425、驱动机构；4251、偏心块；4252、框架；426、第一限位杆；427、第一避让孔；428、第二避让孔；43、第一导向组件；50、机架；61、第二移动机构；62、第二导向组件；621、第一导向柱；622、第一滑动板；63、第二支撑板；70、混匀机构；71、第一支架；72、超声换能器；73、第一导向轮；74、第三导向组件；81、第二温控组件；811、第二加热板；812、第三加热板；813、半导体制冷片；814、散热器；815、散热风扇；82、第二导向轮；83、第四导向组件；90、光学检测模块；91、荧光激发组件；911、荧光发射端；912、二向色镜；913、荧光出射端；92、光纤检测组件；921、检测光纤；922、第三移动机构；923、缓冲座；924、第五导向组件；925、第三支撑板；93、荧光读数组件；931、检测相机；932、滤光片；933、荧光接收端；934、安装座；935、阵列座；936、第四移动机构。
具体实施方式
为使本申请的上述目的、特征和优点能够更加明显易懂，下面结合附图对本申请的具体实施方式做详细的说明。在下面的描述中阐述了很多具体细节以便于充分理解本申请。但是本申请能够以很多不同于在此描述的其它方式来实施，本领域技术人员可以在不违背本申请内涵的情况下做类似改进，因此本申请不受下面公开的具体实施例的限制。
请参阅图1，图1示出了一种封闭式微流控芯片10的结构示意图。封闭式微流控芯片10包括芯片本体11、磁珠(图中未示出)与气体动力组件12。芯片本体11上设有依次连通设置的至少两个预置腔室111。所有相邻预置腔室111均通过第一连通通道112相连通。具体而言，所有相邻预置腔室111之间设有墙板113，所有第一连通通道112均设置于墙板113的顶部部位，所有第一连通通道112均设有相变阀(图中未示出)。此外，所有预置腔室111的口部(如图1中口部位于芯片本体11的顶面)均例如采用密封膜(图1中所示的密封膜隐藏掉，未示出)封堵而呈封闭状态，在预置腔室111的内部设有反应试剂或清洗液。
此外，芯片本体11上还设有进样口与排气口。进样口与排气口均和位于首位的预置腔室111连通。样本液通过进样口注入到位于首位的预置腔室111内，在进样过程中，进入的样本液使得首位的预置腔室111内的气体通过排气口向外排放，芯片本体11上还设有样品检测腔室114，样品检测腔室114与位于末尾的预置腔室111连通。磁珠在磁性装置的作用下在所有预置腔室111中移动。气体动力组件12与末尾的预置腔室111连通，通过提供气压将末尾的预置腔室111内的包括核酸的洗脱液推动到样品检测室。气 体动力组件12也可以与样品检测腔室114相连通，通过提供抽吸力将末尾的预置腔室111内的含有核酸的洗脱液抽吸转移到样品检测腔室114中。
参阅图2至图5，本申请一实施例提供的一种基于封闭式微流控芯片10的核酸提取装置，基于封闭式微流控芯片10的核酸提取装置包括：第一温控组件20、磁吸件30与第一移动机构41。第一温控组件20具有加热机构，加热机构用于对相变阀加热使得相变阀开启以连通两个预置腔室，即第一温控组件20能够对封闭式微流控芯片10的相变阀加热使得相变阀开启。磁吸件30与封闭式微流控芯片10处于预设距离范围内，用于吸附磁珠，且相变阀处于开启状态时，磁吸件30能吸附并带动封闭式微流控芯片10内部的磁珠在所有预置腔室111中移动。磁吸件30包括但不限于永磁铁、电磁铁。第一移动机构41驱动封闭式微流控芯片10或磁吸件30移动，使磁珠在相通的预置腔室111中移动。
上述的基于封闭式微流控芯片10的核酸提取装置，配合封闭式微流控芯片10使用时，将样本液通过进样口注入到位于首位的预置腔室111内，使得样本液在预置腔室111内与储存的试剂发生反应，通过磁珠携带反应后的目标物，并借用磁吸件吸附磁珠，通过第一移动机构41移动微流控芯片或磁吸件，使得磁珠携带目标物移动到下一个预置腔室111，并最终进入到末尾的预置腔室111，在末尾的预置腔室111得到待检测目标物；然后通过气体动力组件12进行动作，使得待检测目标物进入到样品检测腔室114内，便可以在样品检测腔室114完成扩增与检测操作。如此可见，待检测目标物的提取操作，是位于封闭状态的预置腔室111中完成，能够降低操作难度，能避免污染样本，有利于提高检测结果的准确度。
在一个实施例中，第一温控组件20具有对相变阀降温处理使得相变阀阻断两个预置腔室连通的降温机构。如此，当第一温控组件20的加热机构对相变阀加热时，使得相变阀由固态转变为液态，即相变阀开启，这样磁吸件30便能带动吸附住的磁珠穿过液态状态的相变阀进入到相邻的另一个预置腔室111中。反之，当磁珠进入到相邻的另一个预置腔室111中后，通过第一温控组件20的降温机构进行降温，能快速降低相变阀的温度，使得相变阀由液态快速地转变为固态，即相变阀关闭，相变阀关闭时能较好地将两个预置腔室111相互隔离，避免相互影响，从而能保证核酸的提取精度。当然，作为一个可选的方案，相变阀也可以是在所处环境中以自然散热的方式冷却降温。
请参阅图2至图4，在一个实施例中，基于封闭式微流控芯片10的核酸提取装置还包括用于放置封闭式微流控芯片10的第一支撑板42。封闭式微流控芯片10设于第一支撑板42上，第一移动机构41驱动第一支撑板42移动。如此，第一移动机构41驱动第一支撑板42移动时，便相应带动封闭式微流控芯片10移动。
请参阅图3、图4与图6，在一个实施例中，基于封闭式微流控芯片10的核酸提取装置还包括机架50与第一导向组件43。第一导向组件43设置于机架50上，第一支撑板42与第一导向组件43相连。如此，第一移动机构41驱动第一支撑板42移动过程中，在第一导向组件43的导向作用下，第一支撑板42的移动效果较为平稳。
具体而言，第一移动机构41例如设置于机架50上或其它位置，在此不进行限定，只要能实现驱动第一支撑板42移动即可。此外，第一移动机构41包括但不限于丝杆电机、皮带电机、气缸、液压缸，可以根据实际需求进行设置。
另外，第一导向组件43包括但不限于滑轨与滑块配合的滑动导向方式，导向杆与导套的滑动导向方式。
请再参阅图1，一般地，封闭式微流控芯片10包括相连的第一芯片体115(如图1所示的左侧部位)与第二芯片体116(如图1所示的右侧部位)。所有预置腔室111依次设置于第一芯片体115上，样品检测腔室114设置于第二芯片体116上，第一芯片体115的厚度大于第二芯片体116的厚度。此外，为了能对样品检测腔室114进行光学检测，第二芯片体116为透明板材。
请再参阅图1，在一个实施例中，样品检测腔室114设有进液端与出气端，样品检测腔室114的进液端与末尾的预置腔室111连通，样品检测腔室114的出气端具体例如设有防水透气膜。并当需要将末尾的预置腔室111内包括有核酸的洗脱液转移到样品检测腔室114时，通过气体动力组件12作用于末尾的预置腔室111，使得末尾的预置腔室111内的洗脱液推压到样品检测腔室114中，样品检测腔室114内的气体通过防水透气膜向外排放。
请参阅图6，在一个实施例中，第一支撑板42上设有与封闭式微流控芯片10相应的定位槽421。如此，封闭式微流控芯片10放置于第一支撑板42上的定位槽421中时位置相对固定，稳定性较好。
请参阅图6，在一个实施例中，第一支撑板42上还设有两个第一压板422，两个第一压板422分别对应压住封闭式微流控芯片10的第一芯片体115的相对两侧。如此，当封闭式微流控芯片10放置于第一支 撑板42上后，借助两个第一压板422对应压住封闭式微流控芯片10的第一芯片体115的相对两侧，能实现封闭式微流控芯片10稳固地设置于第一支撑板42上，从而能保证核酸的提取与检测效果。此外，由于两个第一压板422压住第一芯片体115的相对两侧，而并没有压设于第一芯片体115的其余区域，这样对预置腔室111的磁珠转移、超声混匀、相变阀状态调整不会造成影响。
当然，作为一个可选的方案，第一压板422也可以是一个或其它数量，当第一压板422为一个时，第一压板422压住于第一芯片体115的其中一侧即可。另外，第一压板422也不限于是必须压在第一芯片体115的侧部部位，还可以是压住于第一芯片体115的其它部位，只要在第一芯片体115上压合的部位不妨碍磁珠转移、超声混匀、相变阀状态调整即可。
其中，第一压板422例如通过紧固件423可拆卸地装设于第一支撑板42上，调整紧固件423的松紧度时便能调整对第一芯片体115的压力大小。紧固件423例如可以是螺钉、螺栓、螺杆等等，在此不进行限定。
请参阅图6，在一个实施例中，第一支撑板42上还设有第二压板424。第二压板424压住封闭式微流控芯片10的第二芯片体116，且第二压板424在第二芯片体116上的压合区域能覆盖封闭式微流控芯片10的防水透气膜，以及能露出封闭式微流控芯片10的样品检测腔室114。如此，当封闭式微流控芯片10放置于第一支撑板42上后，借助第二压板424对应压住封闭式微流控芯片10的第二芯片体116，能实现封闭式微流控芯片10稳固地设置于第一支撑板42上，从而能保证核酸的提取与检测效果。此外，由于第二压板424在第二芯片体116上的压合区域覆盖封闭式微流控芯片10的防水透气膜，即当第二压板424压合于第二芯片体116上时，第二压板424堵住防水透气膜，这样能避免预置腔室111内的液体与样品检测腔室114内的液体相互流动而造成污染，只有当第二压板424离开防水透气膜，在气体动力组件12的动力作用下，才能实现将预置腔室111的洗脱液转移到样品检测腔室114内。另外，由于第二压板424在第二芯片体116上的压合区域露出封闭式微流控芯片10的样品检测腔室114，即第二压板424压住于第二芯片体116上不会对光路造成遮挡，能保证样品检测腔室114的光学检测分析正常开展。
请参阅图6，在一个实施例中，基于封闭式微流控芯片10的核酸提取装置还包括驱动机构425，驱动机构425用于驱动第二压板424运动，第二压板424在驱动机构425的驱动下能压设在封闭式微流控芯片10的防水透气膜上并密闭防水透气膜。具体而言，驱动机构425设置于第一支撑板42上。驱动机构425能够驱动第二压板424升降运动或者水平运动，以使得远离与靠近于封闭式微流控芯片10。如此，通过驱动机构425驱动第二压板424远离于封闭式微流控芯片10时，第二压板424便松开了防水透气膜，样品检测腔室114通过防水透气膜与外界环境连通，进而在气体动力组件12的动力作用下，便能实现末尾的预置腔室111内的洗脱液进入到样品检测腔室114内；并当洗脱液完全进入到样品检测腔室114内后，驱动机构425复位，第二压板424复位并压住封闭式微流控芯片10的第二芯片体116，第二压板424堵住防水透气膜，这样能避免预置腔室111内的液体与样品检测腔室114内的液体相互流动而造成污染。
可选地，驱动机构425的具体设计形式较多，只要能实现驱动第二压板424升降即可，作为一个示例，驱动机构425例如包括设置于第一支撑板42上的电机(未标示)、设置于电机的转轴的偏心块4251、以及设置于第二压板424上的框架4252。电机的转轴驱动偏心块4251转动时能抵触框架4252并驱动框架4252向上移动，框架4252相应带动第二压板424向上运动与封闭式微流控芯片10分离。偏心块4251还能转动到与框架4252相分离的位置，此时第二压板424复位，并压迫于封闭式微流控芯片10上。
请参阅图6，在一个实施例中，第一支撑板42上设有第一限位杆426以及设于第一限位杆426上的第一弹性件(图中未示出)。第二压板424上设有第一活动孔并通过第一活动孔套设于第一限位杆426上，第一限位杆426的头部通过第一弹性件与第二压板424上远离于第一支撑板42的表面相抵触。如此，当驱动机构425驱动第二压板424远离于封闭式微流控芯片10运动时，第二压板424沿着第一限位杆426活动并压缩第一弹性件；当驱动机构425复位时，在第一弹性件的弹力作用下，能实现第二压板424复位并压紧于第二芯片体116上。需要说明的是，第一限位杆426的数量不限于是一个，可以是两个、三个或以上，第二压板424上的活动孔的数量与第一限位杆426的数量相一致。
参阅图3至图5，在一个实施例中，基于封闭式微流控芯片10的核酸提取装置还包括第二移动机构61。第二移动机构61与第一温控组件20、磁吸件30均相连。如此，当第一移动机构41将封闭式微流控芯片10移动到预设位置时，通过第二移动机构61上下移动第一温控组件20或磁吸件30，能实现将磁吸件30移动到贴合预置腔室111顶面的位置以吸附预置腔室111内部的磁珠，也能实现将第一温控组件20移动到相变阀所在的位置，从而对相变阀进行加热或降温。
参阅图1与图5，在一个实施例中，第一温控组件20包括第一加热板21。磁吸件30与第一加热板21 相邻设置，当磁吸件30与任意一个预置腔室111的顶面相贴合接触时，第一加热板21同步与预置腔室111相邻的相变阀靠近。如此，当第二移动机构61驱动磁吸件30运动，使磁吸件30与其中一个预置腔室111的顶面相贴合接触时，磁吸件30能将该预置腔室111内部的磁珠吸附到预置腔室111的顶面，同时由于第一加热板21同步与预置腔室111相邻的相变阀靠近使得该相变阀由固态转变为液态，这样当第一移动机构41驱动封闭式微流控芯片10移动时，便能实现磁珠穿过相变阀进入到相邻的另一个预置腔室111内部，这样能提高核酸提取效率。
参阅图1与图5，在一个实施例中，第一温控组件20还包括降温板22。降温板22、磁吸件30与第一加热板21依次设置。如此，例如当磁吸件30带动磁珠从第一个预置腔室移动到第二个预置腔室111内部时，磁吸件30与第二个预置腔室111的顶面相贴合接触，降温板22同步与第一个预置腔室111与第二预置腔室111之间的相变阀靠近，能降低该相变阀的温度，使得该相变阀由液态转变为固态，即相变阀关闭，进而第一个预置腔室111与第二个预置腔室111相互隔离。
参阅图3至图5，在一个实施例中，基于封闭式微流控芯片10的核酸提取装置还包括机架50与第二导向组件62。第二移动机构61通过第二支撑板63装设于机架50上，第二移动机构61的驱动端通过第二导向组件62分别与第一温控组件20、磁吸件30相连。如此，在第二导向组件62的导向作用下，第一温控组件20与磁吸件30的移动更为稳定，从而能保证核酸的提取效率。
需要说明的是，第二移动机构61类似于第一移动机构41，设计形式较多，在此不进行限定，根据实际需求设置即可。
需要说明的是，第二导向组件62类似于第一导向组件43，主要起到导向作用，具体结构不进行限定，可以根据实际需求进行设置。具体在本实施例中，第二导向组件62包括设置于第二支撑板63上的至少一个第一导向柱621、以及滑动套设于第一导向柱621上的第一滑动板622。第一滑动板622设有滑动孔并通过滑动孔套设于第一导向柱621上。第二移动机构61的驱动端与第一滑动板622相连驱动第一滑动板622移动。第一温控组件20与磁吸件30装设于第一滑动板622上。
参阅图1至图4，在一个实施例中，基于封闭式微流控芯片10的核酸提取装置还包括混匀机构70。混匀机构70用于将封闭式微流控芯片10的预置腔室111内的液体混匀。如此，在核酸裂解、清洗、洗脱过程中，可以根据实际需要，通过混匀机构70接触封闭式微流控芯片10的任意一个预置腔室111时，并使得预置腔室111内的液体混匀，从而能保证核酸的提取效果。
具体而言，混匀机构70包括但不限于超声混匀机构70、震荡混匀机构70等等。
参阅图1、图3、图4与图6，在一个实施例中，混匀机构70包括第一支架71、设置于第一支架71上的超声换能器72、转动地设置于第一支架71上的第一导向轮73。第一支架71通过第二弹性件(图中未示出)设置于机架50或地面上，第一支撑板42设有能露出至少一个预置腔室111的镂空区(图中未示出)，第一支撑板42的侧部设有第一避让孔427，第一移动机构41能驱动第一支撑板42移动到混匀机构70的上方。当第一支撑板42的底面与第一导向轮73相抵触时，超声换能器72与第一支撑板42上放置的封闭式微流控芯片10之间设有间隔；当第一导向轮73移动进入到第一避让孔427中时，超声换能器72与其中一个预置腔室111相接触。如此，第一移动机构41驱动第一支撑板42移动到混匀机构70的上方过程中，当第一导向轮73移动进入到第一避让孔427中时，超声换能器72才与其中一个预置腔室111相接触，并对预置腔室111内的液体混匀；当第一导向轮73没有移动进入到第一避让孔427中，此时第一导向轮73与第一支撑板42的底面接触受到第一支撑板42的重力下压作用，使得第二弹性件发生压缩，超声换能器72与第一支撑板42上放置的封闭式微流控芯片10之间设有间隔，即超声换能器72并没有与预置腔室111相接触，这样超声换能器72便不会将超声能量传递到封闭式微流控芯片10。
参阅图1、图3、图4与图6，在一个实施例中，第一避让孔427的数量与位置与封闭式微流控芯片10的所有预置腔室111一一对应设置。如此，第一支撑板42带动封闭式微流控芯片10移动到混匀机构70的上方过程中，第一导向轮73进入到其中一个第一避让孔427中时，该第一避让孔427所对应的预置腔室111便于与超声换能器72相接触，超声换能器72便可以实现该预置腔室111进行混匀动作。因此，超声换能器72可以与所有预置腔室111的底面均接触，即所有预置腔室111均可以根据实际需求，来通过超声换能器72进行混匀处理。
可以理解的是，作为一个可选的方案，第一避让孔427的设置数量也可以少于封闭式微流控芯片10的预置腔室111的数量，在此不进行限定。
参阅图1、图3、图4与图6，在一个实施例中，第一支架71的相对两侧均设有第一导向轮73，第一支撑板42的相对两侧均设有第一避让孔427，第一支架71的两个第一导向轮73能够同步分别对应进入到 两个第一避让孔427中。如此，第一支撑板42在混匀机构70上方移动过程中，当两个第一导向轮73并没有移动进入到两个第一避让孔427中时，第一支撑板42同步与两个第一导向轮73相接触，第一支撑板42的运动稳定性较好。
参阅图3、图4与图6，在一个实施例中，混匀机构70还包括第三导向组件74。第一支架71通过第三导向组件74与机架50或地面相连。如此，在第三导向组件74的导向作用下，第一支架71的升降方式为直线升降，平稳性较好。需要说明的是，第三导向组件74的具体组合形式类似于第一导向组件43，在此不进行限定。此外，第三导向组件74可以设置为一个、两个、三个或其它数量。另外，第二弹性件例如为弹簧，弹簧套设于第三导向组件74外，第二弹性件的一端与第一支架71相连，另一端与第三导向组件74相连或与机架50相连。
参阅图1、图3与图4，在一个实施例中，基于封闭式微流控芯片10的核酸提取装置还包括第二温控组件81。第二温控组件81能够对封闭式微流控芯片10的样品检测腔室114进行加热。如此，当洗脱液进入到样品检测腔室114内后，通过第二温控组件81对样品检测腔室114内的洗脱液采用高温与低温循环加热，从而能实现核酸扩增。
参阅图1、图3与图4，在一个实施例中，第二温控组件81包括间隔设置的第二加热板811与第三加热板812。第二加热板811加热的温度高于第三加热板812加热的温度，第二加热板811与第三加热板812循环交替给样品检测腔室114加热。如此，第二加热板811与第三加热板812构成双温区加热，减少了热源变温需要的时间，提高了液体的升温和降温速率，缩短了扩增检测时间。
参阅图1、图3与图4，在一个实施例中，第二温控组件81还包括两个半导体制冷片813、散热器814与散热风扇815。其中一半导体制冷片813置于第二加热板811和散热器814间，另一半导体制冷片813置于第三加热板812和散热器814间。散热器814与散热风扇815相连。
当然，第二加热板811与第三加热板812还可以通过其它方式进行加热，例如通过电热丝的方式进行导热，在此不进行限定，根据实际需求进行设置即可。
参阅图1、图3与图4，在一个实施例中，第二温控组件81通过第三弹性件(图中未示出)设置于机架50或地面上，第二温控组件81设有第二导向轮82，第一支撑板42的侧部设有第二避让孔428，第一移动机构41能驱动第一支撑板42移动到第二温控组件81的上方。当第一支撑板42的底面与第二导向轮82相抵触时，第二加热板811、第三加热板812均与第一支撑板42上放置的封闭式微流控芯片10之间设有间隔；当第二导向轮82移动进入到第二避让孔428中时，第二加热板811或第三加热板812与样品检测腔室114相接触。如此，第一移动机构41驱动第一支撑板42移动到第二温控组件81的上方过程中，当第二导向轮82移动进入到第二避让孔428中时，第二加热板811或第三加热板812与样品检测腔室114相接触，并对样品检测腔室114内的核酸加热扩增；当第二导向轮82没有移动进入到第二避让孔428中，此时第二导向轮82与第一支撑板42的底面接触受到第一支撑板42的重力下压作用，使得第三弹性件发生压缩，第二加热板811、第三加热板812均与第一支撑板42上放置的封闭式微流控芯片10之间设有间隔，即第二加热板811与第三加热板812均没有与样品检测腔室114相接触，这样第二温控组件81便不会将热量传递到样品检测腔室114。
类似地，第二温控组件81通过第四导向组件83设置于机架50上，在第四导向组件83的导向作用下，第二温控组件81的移动更加平稳。
参阅图6，在一个实施例中，第二避让孔428为至少两个，所有第二避让孔428沿着第一支撑板42的侧部依次设置。具体而言，第一支撑板42带动封闭式微流控芯片10移动到第二温控组件81的上方过程中，第二导向轮82依次进入到各个第二避让孔428中时，第二加热板811与第三加热板812会先后与样品检测腔室114相接触，实现对样品检测腔室114依次加热。
参阅图1、图3与图4，此外，当预置腔室111需要通过第二温控组件81加热时，即在第一支撑板42上设置的第二避让孔428便不止是两个，并设置有与预置腔室111相对应的第二避让孔428，当第二导向轮82进入到与预置腔室111相应的第二避让孔428中时，第二温控组件81的加热板能接触预置腔室111，便可以将热量传递给预置腔室111。
请参阅图3、图7至图9，在一个实施例中，基于封闭式微流控芯片10的核酸提取装置还包括光学检测模块90。光学检测模块90用于对样品检测腔室114内的核酸进行光学检测。
请参阅图3、图7至图9，在一个实施例中，光学检测模块90包括荧光激发组件91、光纤检测组件92与荧光读数组件93。荧光激发组件91用于产生荧光，并将产生的荧光发射到光纤检测组件92，光纤检测组件92用于将荧光导入到样品检测腔室114的核酸，并将经样品检测腔室114中的核酸反射的光线导 入给荧光读数组件93。
请参阅图7至图9，在一个实施例中，荧光激发组件91包括荧光发射端911、二向色镜912与荧光出射端913。荧光发射端911产生的荧光入射到二向色镜912，依次经过二向色镜912与荧光出射端913向外射出。
请参阅图7至图9，在一个实施例中，光纤检测组件92包括第一传输光纤(图中未示出)、检测光纤921与第二传输光纤(图中未示出)。第一传输光纤两端分别连接荧光出射端913、检测光纤921，第二传输光纤两端分别连接检测光纤921与荧光读数组件93的荧光接收端933，检测光纤921对着样品检测腔室114。
请参阅图7至图9，在一个实施例中，荧光读数组件93包括依次设置的检测相机931、滤光片932与荧光接收端933。样品检测腔室114的样品反射的荧光经过检测光纤921传输给荧光接收端933，荧光接收端933用于将荧光传输给滤光片932，经滤光片932过滤后入射到检测相机931。
请参阅图7至图9，在一个实施例中，光纤检测组件92还包括设置于机架50上的第三移动机构922与缓冲座923。第三移动机构922与缓冲座923相连，第三移动机构922用于驱动缓冲座923移动到第一支撑板42上，检测光纤921设置于缓冲座923上。如此，当第一支撑板42带动封闭式微流控芯片10移动到光纤检测组件92的正下方时，通过第三移动机构922驱动缓冲座923移动，缓冲座923通过接触第一支撑板42而移动到位并起到缓冲作用，检测光纤921对着封闭式微流控芯片10上的样品检测腔室114，便能实现将荧光入射到样品检测腔室114内的核酸样品表面，并接收由核酸样品表面反射回的荧光。
需要说明的是，具体本实施例中，第一支撑板42上设置有第二压板424，缓冲座923向下移动抵住第二压板424后定位，即缓冲座923间接接触第一支撑板42。
还需要说明的是，第三移动机构922类似于第一移动机构41，不限定其具体结构形式，只要能实现驱动缓冲座923移动即可。此外，第三移动机构922通过第三支撑板925装设于机架50，并在第三支撑板925上设置有第五导向组件924，第五导向组件924与缓冲座923相连，这样第三移动机构922驱动缓冲座923移动时，第五导向组件924进行导向，缓冲座923运动更加平稳。
在一个实施例中，荧光读数组件93还包括安装座934、设置于安装座934上的第四移动机构、以及可移动地设置于安装座934上的阵列座935。第四移动机构与阵列座935相连，用于驱动阵列座935移动。荧光发射端911为至少两个，滤光片932为至少两个并与荧光发射端911一一对应设置。所有滤光片932均依次地设置于阵列座935上，第四移动机构驱动阵列座935移动时，能使得阵列座935上的滤光片932依次与荧光接收端933对位。如此，依次点亮荧光发射端911，在荧光发射端911点亮时，通过第四移动机构驱动阵列座935移动，使得与荧光发射端911所对应的滤光片932移动到与荧光接收端933对位的位置，这样便能够在短时间内实现多重光路的切换检测，在保证准确性的前提下减少了检测时间，提高了检测速度。
在一个实施例中，一种基于封闭式微流控芯片10的核酸提取方法，采用了上述任一实施例的基于封闭式微流控芯片10的核酸提取装置，包括如下步骤：
步骤S10、配合封闭式微流控芯片10使用时，磁吸件吸附携带目标物的磁珠，第一温控组件20对封闭式微流控芯片10的相变阀加热使得相变阀开启；
步骤S20、通过第一移动机构41移动微流控芯片或磁吸件，使得携带目标物的磁珠从其中一个预置腔室111穿过处于开启状态的相变阀移动到下一个预置腔室111。
上述的基于封闭式微流控芯片10的核酸提取方法，目标物的提取操作，是位于封闭状态的预置腔室111中完成，能够降低操作难度，能避免污染样本，有利于提高检测结果的准确度。
在一实施例中，基于封闭式微流控芯片10的核酸提取方法还包括步骤：
步骤S30、当携带目标物的磁珠从其中一个预置腔室111穿过处于开启状态的相变阀移动到下一个预置腔室111时，通过第一温控组件20对处于开启状态的相变阀进行降温，使得相变阀从液态变化固态而关闭。
步骤S40、当相变阀关闭后，驱动磁吸件远离封闭式微流控芯片10，并移动封闭式微流控芯片10或混匀机构70，使得混匀机构70接触有磁珠的预置腔室111，通过混匀机构70对该预置腔室111的液体进行混匀。
步骤S50、重复执行上述步骤S10至步骤S40，直到磁珠携带目标物进入到末尾的预置腔室111中。
步骤S60、在气体动力组件12的动力作用下，将末尾的预置腔室111内的洗脱液推入到样品检测腔室114中；
步骤S70、移动封闭式微流控芯片10或第二温控组件81，使第二温控组件81接触样品检测腔室114；第二温控组件81提供两种不同预设温度，以两种不同预设温度交替工作并传递热量给样品检测腔室114。
该两种不同预设温度分别为高温与低温，具体大小可以根据实际情况进行设置，通过第二温控组件81以两种不同预设温度循环交替接触样品检测腔室114，能实现将样品检测腔室114内的核酸进行扩增。
步骤S80、通过第二温控组件81对样品检测腔室114内的加热到预设时间后，移动封闭式微流控芯片10或光学检测模块90，使得光学检测模块90能够与样品检测腔室114对位，并对样品检测腔室114内的核酸进行光学检测。
以上实施例的各技术特征可以进行任意的组合，为使描述简洁，未对上述实施例中的各个技术特征所有可能的组合都进行描述，然而，只要这些技术特征的组合不存在矛盾，都应当认为是本说明书记载的范围。
以上所述实施例仅表达了本申请的几种实施方式，其描述较为具体和详细，但并不能因此而理解为对申请专利范围的限制。应当指出的是，对于本领域的普通技术人员来说，在不脱离本申请构思的前提下，还可以做出若干变形和改进，这些都属于本申请的保护范围。因此，本申请专利的保护范围应以所附权利要求为准。
在本申请的描述中，需要理解的是，术语“中心”、“纵向”、“横向”、“长度”、“宽度”、“厚度”、“上”、“下”、“前”、“后”、“左”、“右”、“竖直”、“水平”、“顶”、“底”、“内”、“外”、“顺时针”、“逆时针”、“轴向”、“径向”、“周向”等指示的方位或位置关系为基于附图所示的方位或位置关系，仅是为了便于描述本申请和简化描述，而不是指示或暗示所指的装置或元件必须具有特定的方位、以特定的方位构造和操作，因此不能理解为对本申请的限制。
此外，术语“第一”、“第二”仅用于描述目的，而不能理解为指示或暗示相对重要性或者隐含指明所指示的技术特征的数量。由此，限定有“第一”、“第二”的特征可以明示或者隐含地包括至少一个该特征。在本申请的描述中，“多个”的含义是至少两个，例如两个，三个等，除非另有明确具体的限定。
在本申请中，除非另有明确的规定和限定，术语“安装”、“相连”、“连接”、“固定”等术语应做广义理解，例如，可以是固定连接，也可以是可拆卸连接，或成一体；可以是机械连接，也可以是电连接；可以是直接相连，也可以通过中间媒介间接相连，可以是两个元件内部的连通或两个元件的相互作用关系，除非另有明确的限定。对于本领域的普通技术人员而言，可以根据具体情况理解上述术语在本申请中的具体含义。
在本申请中，除非另有明确的规定和限定，第一特征在第二特征“上”或“下”可以是第一和第二特征直接接触，或第一和第二特征通过中间媒介间接接触。而且，第一特征在第二特征“之上”、“上方”和“上面”可是第一特征在第二特征正上方或斜上方，或仅仅表示第一特征水平高度高于第二特征。第一特征在第二特征“之下”、“下方”和“下面”可以是第一特征在第二特征正下方或斜下方，或仅仅表示第一特征水平高度小于第二特征。
需要说明的是，当元件被称为“固定于”或“设置于”另一个元件，它可以直接在另一个元件上或者也可以存在居中的元件。当一个元件被认为是“连接”另一个元件，它可以是直接连接到另一个元件或者可能同时存在居中元件。本文所使用的术语“垂直的”、“水平的”、“上”、“下”、“左”、“右”以及类似的表述只是为了说明的目的，并不表示是唯一的实施方式。

Claims (16)

  1. 一种基于封闭式微流控芯片的核酸提取装置，所述封闭式微流控芯片包括磁珠以及多个相连通的预置腔室，所述磁珠置于所述预置腔室中，两个预置腔室的相连通处设有控制通断的相变阀；所述基于封闭式微流控芯片的核酸提取装置包括：
    第一温控组件，所述第一温控组件具有加热机构，所述加热机构用于对所述相变阀加热使得所述相变阀开启以连通所述两个预置腔室；
    磁吸件，所述磁吸件与所述封闭式微流控芯片处于预设距离范围内，用于吸附所述磁珠；
    第一移动机构，所述第一移动机构驱动所述封闭式微流控芯片或所述磁吸件移动，使所述磁珠在相通的预置腔室中移动。
  2. 根据权利要求1所述的基于封闭式微流控芯片的核酸提取装置，其中，所述第一温控组件具有对所述相变阀降温处理使得所述相变阀阻断所述两个预置腔室连通的降温机构。
  3. 根据权利要求1所述的基于封闭式微流控芯片的核酸提取装置，其中，所述基于封闭式微流控芯片的核酸提取装置还包括用于放置所述封闭式微流控芯片的第一支撑板；所述第一移动机构驱动所述第一支撑板移动。
  4. 根据权利要求3所述的基于封闭式微流控芯片的核酸提取装置，其中，所述基于封闭式微流控芯片的核酸提取装置还包括机架与第一导向组件；所述第一导向组件设置于所述机架上，所述第一支撑板与所述第一导向组件相连；
    和/或，所述第一支撑板上设有两个第一压板，两个第一压板分别对应压住所述封闭式微流控芯片相对两侧；
    和/或，所述第一支撑板上设有第二压板以及用于驱动第二压板运动的驱动机构，所述第二压板在所述驱动机构的驱动下能压设在所述封闭式微流控芯片的防水透气膜上并密闭所述防水透气膜。
  5. 根据权利要求3所述的基于封闭式微流控芯片的核酸提取装置，其中，所述基于封闭式微流控芯片的核酸提取装置还包括第二移动机构；所述第二移动机构与所述第一温控组件、所述磁吸件均相连；
    和/或，所述加热机构包括第一加热板，所述磁吸件与所述第一加热板相邻设置。
  6. 根据权利要求3所述的基于封闭式微流控芯片的核酸提取装置，其中，所述基于封闭式微流控芯片的核酸提取装置还包括用于将所述预置腔室内的液体混匀的混匀机构。
  7. 根据权利要求6所述的基于封闭式微流控芯片的核酸提取装置，其中，所述混匀机构包括第一支架、设置于第一支架上的超声换能器、转动地设置于第一支架上的第一导向轮；所述第一支架通过第二弹性件设置于机架或地面上，所述第一支撑板设有能露出至少一个所述预置腔室的镂空区，所述第一支撑板的侧部设有第一避让孔；所述第一移动机构驱动所述第一支撑板移动到所述混匀机构的上方，当所述第一支撑板的底面与所述第一导向轮相抵触时，所述超声换能器与所述第一支撑板上放置的所述封闭式微流控芯片之间设有间隔；当所述第一导向轮移动进入到所述第一避让孔中时，所述超声换能器与其中一个所述预置腔室相接触。
  8. 根据权利要求7所述的基于封闭式微流控芯片的核酸提取装置，其中，所述第一避让孔的数量和位置与所有所述预置腔室一一对应；
    和/或，所述混匀机构还包括第三导向组件，所述第一支架通过所述第三导向组件与所述机架或所述地面相连。
  9. 根据权利要求3所述的基于封闭式微流控芯片的核酸提取装置，其中，所述基于封闭式微流控芯片的核酸提取装置还包括第二温控组件，所述第二温控组件能够对所述封闭式微流控芯片的样品检测腔室进行加热。
  10. 根据权利要求9所述的基于封闭式微流控芯片的核酸提取装置，其中，所述第二温控组件包括间隔设置的第二加热板与第三加热板，所述第二加热板加热的温度高于所述第三加热板加热的温度，所述第二加热板与所述第三加热板循环交替给所述样品检测腔室加热。
  11. 根据权利要求10所述的基于封闭式微流控芯片的核酸提取装置，其中，所述第二温控组件还包括两个半导体制冷片、散热器与散热风扇；其中一半导体制冷片置于所述第二加热板和所述散热器间，另一半导体制冷片置于第三加热板和所述散热器间，所述散热器与所述散热风扇相连；
    和/或，所述第二温控组件通过第三弹性件设置于机架或地面上，所述第二温控组件设有第二导向轮，所述第一支撑板的侧部设有第二避让孔，所述第一移动机构能驱动所述第一支撑板移动到所述第二温控组 件的上方；当所述第一支撑板的底面与所述第二导向轮相抵触时，所述第二加热板、所述第三加热板均与所述第一支撑板上放置的所述封闭式微流控芯片之间设有间隔；当所述第二导向轮移动进入到所述第二避让孔中时，所述第二加热板或所述第三加热板与所述样品检测腔室相接触。
  12. 根据权利要求3所述的基于封闭式微流控芯片的核酸提取装置，其中，所述基于封闭式微流控芯片的核酸提取装置还包括光学检测模块；所述光学检测模块用于对样品检测腔室内的核酸进行光学检测。
  13. 根据权利要求12所述的基于封闭式微流控芯片的核酸提取装置，其中，所述光学检测模块包括荧光激发组件、光纤检测组件与荧光读数组件；所述荧光激发组件用于产生荧光，并将产生的荧光发射到所述光纤检测组件，所述光纤检测组件用于将荧光导入到样品检测腔室，并将经所述样品检测腔室中的核酸反射的光线导入给所述荧光读数组件。
  14. 根据权利要求13所述的基于封闭式微流控芯片的核酸提取装置，其中，所述荧光激发组件包括荧光发射端、二向色镜与荧光出射端；所述荧光发射端产生的荧光入射到所述二向色镜，依次经过所述二向色镜与所述荧光出射端向外射出；
    所述光纤检测组件包括第一传输光纤、检测光纤与第二传输光纤；所述第一传输光纤两端分别连接所述荧光出射端、所述检测光纤，所述第二传输光纤两端分别连接所述检测光纤与所述荧光读数组件的荧光接收端，所述检测光纤对着所述样品检测腔室；
    所述荧光读数组件包括依次设置的检测相机、滤光片与荧光接收端，所述样品检测腔室的样品反射的荧光经过所述检测光纤传输给所述荧光接收端，所述荧光接收端用于将荧光传输给所述滤光片，经所述滤光片过滤后入射到所述检测相机。
  15. 根据权利要求14所述的基于封闭式微流控芯片的核酸提取装置，其中，所述光纤检测组件还包括设置于机架上的第三移动机构与缓冲座；所述第三移动机构与所述缓冲座相连，所述第三移动机构用于驱动所述缓冲座移动到所述第一支撑板上，所述检测光纤设置于所述缓冲座上；
    和/或，所述荧光读数组件还包括安装座、设置于安装座上的第四移动机构、以及可移动地设置于安装座上的阵列座；所述第四移动机构与所述阵列座相连，用于驱动阵列座移动；所述荧光发射端为至少两个，所述滤光片为至少两个并与所述荧光发射端一一对应设置；所有所述滤光片均依次地设置于所述阵列座上，所述第四移动机构驱动所述阵列座移动时，能使得所述阵列座上的所述滤光片依次与所述荧光接收端对位。
  16. 一种基于封闭式微流控芯片的核酸提取方法，其中，采用了如权利要求1至15任意一项所述的基于封闭式微流控芯片的核酸提取装置，包括如下步骤：
    步骤S10、配合封闭式微流控芯片使用时，磁吸件吸附携带目标物的磁珠，第一温控组件对封闭式微流控芯片的相变阀加热使得所述相变阀开启；
    步骤S20、通过第一移动机构移动微流控芯片或磁吸件，使得携带目标物的磁珠从其中一个所述预置腔室穿过处于开启状态的相变阀移动到下一个预置腔室。
PCT/CN2022/128188 2021-12-02 2022-10-28 基于封闭式微流控芯片的核酸提取装置与方法 WO2023098363A1 (zh)

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