WO2023206096A1 - 液体转移装置及多路并联的液体转移装置 - Google Patents

液体转移装置及多路并联的液体转移装置 Download PDF

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Publication number
WO2023206096A1
WO2023206096A1 PCT/CN2022/089375 CN2022089375W WO2023206096A1 WO 2023206096 A1 WO2023206096 A1 WO 2023206096A1 CN 2022089375 W CN2022089375 W CN 2022089375W WO 2023206096 A1 WO2023206096 A1 WO 2023206096A1
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WIPO (PCT)
Prior art keywords
liquid
valve
chamber
transfer device
channel
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PCT/CN2022/089375
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English (en)
French (fr)
Inventor
蒋太交
梁松松
耿鹏
李胜光
张辉
马然
Original Assignee
广州国家实验室
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Application filed by 广州国家实验室 filed Critical 广州国家实验室
Priority to PCT/CN2022/089375 priority Critical patent/WO2023206096A1/zh
Publication of WO2023206096A1 publication Critical patent/WO2023206096A1/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
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/02—Burettes; Pipettes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • 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
    • 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
    • C12Q1/70—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving virus or bacteriophage

Definitions

  • the present disclosure relates to the technical field of biomedical instruments, and specifically to a liquid transfer device and a multi-channel parallel liquid transfer device.
  • liquid chemical reagents such as ether and phenol
  • Some liquid chemical reagents are volatile and toxic. drugs; or, some microbial pathogens that can easily cause infections, allergies, tumors and other diseases, such as viruses, bacteria, rickettsiae, mycoplasma, chlamydia, spirochetes, fungi, actinomycetes, etc., during the transfer process, most use
  • the most common methods are open suction and transfer devices, or pouring between reagent bottles. In this way, airtight operation cannot be achieved during the reagent transfer process, so it is easy to cause volatile toxic reagents to volatilize and spread to the outside of the container, contaminating the outside. environment and endangering the personal safety of operators.
  • nucleic acid detection has the characteristics of high sensitivity and good specificity, and has important applications in disease diagnosis, epidemic prevention and control, health monitoring and other fields.
  • nucleic acid detection technology mainly includes the following two detection forms:
  • the first is traditional manual detection, which involves manually operating a pipette to repeatedly add various biochemical reaction reagents to PCR reaction tubes and transfer samples.
  • This method needs to be completed under negative pressure conditions and relies on the manual operation of professional testing personnel.
  • Rigid reagent tubes made of glass and other materials are usually used during sample storage, extraction or transfer. Sample extraction or transfer is inconvenient, and the operation process is complex and automated. The degree is not high, and samples are prone to cross-contamination during testing or transfer, leading to a series of problems such as false positive results; and in an open environment, testing personnel are prone to increase the probability of virus infection.
  • the second type is automated detection equipment.
  • Most of the nucleic acid automatic detection equipment currently on the market use independent methods in the nucleic acid extraction, amplification and detection steps, that is, each step requires independent equipment to complete, and a nucleic acid detection The process requires multiple pieces of equipment to operate. On the one hand, multiple devices take up a lot of space. On the other hand, the samples after completing the previous steps need to be transferred to subsequent devices, which is cumbersome and time-consuming.
  • most of the existing nucleic acid detection equipment uses solenoid valves. To control liquid transfer, a solenoid valve is used. The valve core is in contact with the reagent, and the valve core needs to move, which will inevitably produce a certain gap. Therefore, the reagent will have the risk of leakage, and it is also susceptible to external damage during the sample transfer process. Environmental pollution or contamination detection environment.
  • nucleic acid testing equipment has also gradually appeared, including fully automatic nucleic acid testing equipment that integrates extraction, amplification and detection.
  • detection Equipment can only extract one sample at a time for detection of a single pathogen, such as Cepheid's GeneXpert, bioMérieux's FilmArray, etc. The detection throughput and efficiency of the above-mentioned products are low.
  • embodiments of the present disclosure provide a liquid transfer device and a multi-path parallel liquid transfer device.
  • embodiments of the present disclosure provide a liquid transfer device.
  • the liquid transfer device includes:
  • the liquid circuit valve plate has a valve membrane covering area at the bottom, and the valve membrane covering area is provided with at least one pipetting channel and a plurality of valve holes; there is a first preset distance between the valve hole and the pipetting channel;
  • the cartridge body is fixed on the top of the liquid circuit valve plate.
  • the cartridge body includes a plurality of reagent tubes, and each reagent tube is connected to one of the valve holes;
  • An elastic valve membrane covers the valve membrane covering area;
  • the elastic valve membrane has a plurality of first preset areas, and a plurality of membrane valves are formed between the first preset areas and the liquid circuit valve plate for Connect or block the valve hole and the pipetting channel;
  • a driving component is used to open or close the membrane valve.
  • the liquid circuit valve plate is provided with a plurality of grooves, and the grooves are covered by the elastic valve film to form the pipetting channel.
  • the pipetting channel has a branch portion extending toward the valve hole.
  • the elastic valve membrane also has a plurality of second preset areas; a plurality of the membrane valves are formed between the second preset areas and the liquid circuit valve plate for conducting or blocking phases.
  • the driving assembly includes: several driving parts;
  • Each driving member includes: a shell body, a push-pull rod located in the shell body, and a film; the film is fixed at the opening of the shell body, one side is connected to the push-pull rod, and the other side is connected to the elastic valve membrane. connect.
  • the elastic valve membrane is laid on the liquid path valve plate in an integral or separate form.
  • the liquid path valve plate is also provided with a liquid outlet and a liquid outlet channel;
  • One end of the liquid outlet channel is connected to the liquid outlet, and the other end is connected to one of the valve holes, and is controlled by the membrane valve to achieve communication or blocking with the pipetting channel.
  • the top of the liquid circuit valve plate has a first film-coated area; the first film-coated area is provided with the liquid outlet channel.
  • the liquid circuit valve plate is further provided with at least one liquid receiving pipe; the liquid receiving pipe is in communication with the liquid outlet.
  • the liquid valve plate is also provided with a gas connector; the gas connector is connected to one of the valve holes, and is controlled by the membrane valve to achieve communication or blocking with the pipetting channel. .
  • the liquid line valve plate is further provided with a quantitative cell, which is disposed between two adjacent reagent tubes and located in the pipetting channel.
  • some of the reagent tubes have built-in piston push rods.
  • the reagent tube is a sealed chamber, including a waste liquid chamber, a sample chamber, a lysis chamber, an empty chamber, a washing liquid chamber, an eluent chamber, a magnetic elution chamber, a mixing tube, and mineral oil arranged in sequence. room, excess room, and secondary adding room.
  • the sealed chamber is sealed by a sealing member selected from a film or a piston.
  • the first pipetting channel is used for liquid transfer in the waste liquid chamber, sample chamber, lysis chamber, empty chamber, washing liquid chamber, and eluate liquid chamber
  • the second pipetting channel The channel is used for liquid transfer in the magnetic elution chamber and mixing tube
  • the third pipetting channel is used for liquid transfer in the mineral oil chamber and excess chamber
  • the fourth pipetting channel is used in the secondary sample addition chamber. of liquid transfer.
  • the liquid circuit valve plate is also provided with a quantitative tank located in the pipetting channel between the mineral oil chamber and the excess chamber.
  • the elastic valve membrane also has three second preset areas; three membrane valves are formed between the second preset areas and the liquid circuit valve plate, respectively used for conducting or blocking. Disconnect the adjacent first pipetting channel and the second pipetting channel, the adjacent second pipetting channel and the third pipetting channel, and the adjacent third pipetting channel and the fourth pipetting channel. liquid channel.
  • embodiments of the present disclosure provide a multi-channel parallel liquid transfer device.
  • each of the multiple parallel-connected liquid transfer devices includes the liquid transfer device according to any one of the first aspects.
  • the liquid transfer device includes: a liquid path valve plate with a valve membrane covering area at the bottom, and the valve membrane covering area is provided with at least one pipetting channel and a plurality of valve holes; the valve hole and the pipetting channel There is a first preset distance between them; the cartridge body is fixed on the top of the liquid line valve plate, the cartridge body includes a plurality of reagent tubes, each reagent tube is connected to one of the valve holes; the elastic valve membrane , covering the valve membrane covering area; the elastic valve membrane has several first preset areas, and several membrane valves are formed between the first preset areas and the liquid circuit valve plate for conduction or Block the valve hole and the pipetting channel; drive component for opening or closing the membrane valve.
  • the sample transfer process of the present disclosure is carried out in a fully closed state, and liquid reagents can be transferred and detected in a non-negative pressure biological experimental environment to avoid the risk of cross-infection caused by aerosols; the reagents are pre-installed in the reagent tubes and passed through
  • the driving component controls the elastic membrane valve to move in the direction of the reagent tube, closes the membrane valve, makes the elastic membrane valve close to the fluid outlet of the reagent tube, and seals the reagent in the reagent tube in the reagent tube; when in use, the driving component controls the elastic membrane valve to move in the opposite direction to the reagent tube.
  • liquid samples can be transferred and detected in each channel individually, or multiple channels of different individual samples can be transferred and detected simultaneously, which has a high degree of automation and improves the transfer and detection throughput. and transfer and detection efficiency.
  • Figure 1 shows a perspective view of a liquid transfer device according to an embodiment of the present disclosure.
  • Figure 2 shows an exploded view of a liquid transfer device in accordance with an embodiment of the present disclosure.
  • Figure 3 shows a schematic diagram of the positional relationship between the cartridge body and the liquid circuit valve plate according to an embodiment of the present disclosure.
  • Figure 4 shows a schematic diagram of the positional relationship between the elastic valve membrane and the liquid circuit valve plate according to an embodiment of the present disclosure.
  • FIG. 5 shows a schematic diagram of the positional relationship between the driving assembly and the hydraulic valve plate according to an embodiment of the present disclosure.
  • Figure 6 shows a schematic structural diagram of a driving assembly according to an embodiment of the present disclosure.
  • connection can be a fixed connection, a detachable connection, or an integral body; It can be a mechanical connection or an electrical connection; it can be a direct connection or an indirect connection through an intermediate medium; it can be an internal connection between two elements or an interactive relationship between two elements, unless otherwise clearly limited.
  • connection can be a fixed connection, a detachable connection, or an integral body; It can be a mechanical connection or an electrical connection; it can be a direct connection or an indirect connection through an intermediate medium; it can be an internal connection between two elements or an interactive relationship between two elements, unless otherwise clearly limited.
  • the present disclosure is made to address, at least in part, problems in the prior art identified by the inventors.
  • the liquid transfer device 100 includes: a cartridge body 110 , a liquid circuit valve plate 120 , an elastic valve membrane 130 , and a driving assembly 140 .
  • the cartridge body 110 is located on the top of the liquid line valve plate 120.
  • the cartridge body 110 and the liquid line valve plate 120 can be integrally formed or assembled for use as one body.
  • the bottom of the liquid line valve plate 120 has a valve film covering area P, and the elastic valve film 130 For example, it is covered on the valve diaphragm covering area P by bonding.
  • the driving component 140 is located under the elastic valve diaphragm 130 and is connected to the elastic valve diaphragm 130 by ultrasonic welding, for example.
  • the cartridge body 110 includes several reagent tubes 111, which are fixed on the top of the liquid circuit valve plate 120.
  • the figure shows two types of reagent tubes 111, namely reagent tubes 01, 02, 03, 04, 05, 06, 07, 08, 012 and reagent tubes 09, 010, 011, 013.
  • reagent tubes 09, 10, 011, 013 have built-in piston push rods 112 (see Figure 2), and reagent tubes 01-08, 012 are Configured as a sealed chamber.
  • the applicant will further explain the application scenario of nucleic acid extraction using the magnetic bead method, which will not be described again.
  • the liquid circuit valve plate 120 is provided with valve holes b matching the number of reagent tubes 111, that is, valve holes b1, b2, b3, ..., b13.
  • Each valve hole b is connected to one reagent tube 111.
  • the valve hole b1 is connected to the reagent tube 01
  • the valve hole b2 is connected to the reagent tube 02, and so on.
  • At least one pipetting channel 121 is provided in the valve membrane covering area p of the liquid line valve plate 120.
  • the pipetting channel 121 has a first preset distance from the valve hole b.
  • the elastic valve membrane 130 has several first preset areas P1. , when the elastic valve membrane 130 covers the valve membrane covering area p, a plurality of membrane valves are formed between a plurality of first preset areas P1 and the liquid path valve plate 120. When the membrane valve is closed, the pipetting channel 121 and the valve hole The gap b is blocked by the elastic valve membrane 130, so the two cannot be connected.
  • the liquid reagent pre-disposed in the reagent tube 111 cannot flow into the pipetting channel 121 through the valve hole b.
  • the first preset area A gap is formed between P1 and the liquid circuit valve plate 120 to connect the pipetting channel 121 and the valve hole b.
  • the liquid reagent pre-disposed in the reagent tube 111 flows through the gap from the valve hole b and flows into the pipetting channel 121 .
  • the driving assembly 140 provides a force to open or close the membrane valve.
  • the first preset area p1 covers both the valve hole b and part of the pipetting channel 121, and the part outside the first preset area p1, such as the shaded part in the figure, is welded to the valve membrane. Covering the area p, thereby ensuring that only a gap is formed between the first preset area p1 and the liquid path valve plate 120 under the action of external force, and the liquid in the reagent tube 111 will not leak from the edge of the elastic valve membrane 130.
  • the elastic valve membrane 130 also has a second preset area p2.
  • Several membrane valves are formed between the second preset area p2 and the liquid circuit valve plate 120 for conducting or blocking adjacent areas. Two pipetting channels; wherein, there is a second preset distance between two adjacent pipetting channels.
  • the area covered by the second preset area p2 on the liquid line valve plate 120 is the p3 area.
  • the elastic valve film 130 covers the p3 area, a plurality of second preset areas p2 and the liquid line valve plate 120 are formed.
  • the ends of two adjacent pipetting channels 121 are located in the p3 area. There is no conduction between these two pipetting channels 121.
  • the membrane valve is closed, the gap between the two adjacent pipetting channels 121 Because the elastic valve membrane 130 is blocked, that is, the liquid in the reagent tube 111 cannot be transferred through the two pipetting channels 121. For example, the liquid cannot be transferred between the reagent tubes 07 and 08.
  • the second preset area A gap is formed between P2 and the liquid circuit valve plate 120 to conduct two adjacent pipetting channels 121, for example, the gap between the pipetting channels where the reagent tubes 07 and 08 are located, and the liquid in the reagent tube 07 can flow to the reagent tube through the gap. 08.
  • the reagent tube 111 is divided into different functional areas according to the corresponding pipetting channels 121. Liquid transfer can be carried out in the same functional area through a common pipetting channel 121, and between different functional areas through the second preset
  • the control of the membrane valve formed between the area p2 and the liquid path valve plate 120 realizes liquid transfer.
  • the passage with other functional areas can be cut off by closing the membrane valve of the second preset area of the corresponding functional area to avoid the impact of liquid transfer on other functional areas.
  • the membrane valve in the area in other words, the liquid transfer between reagent tubes b11 and b12 can also be carried out independently without being affected by the liquid transfer between reagent tubes 07 and 08.
  • the elastic valve membrane 130 is laid on the liquid circuit valve plate 120 in an integral or separate form to form several membrane valves.
  • the driving assembly 140 includes a plurality of driving parts 141 , such as driving parts c1, c2...c13, driving parts c1, c2...c13 and valve holes b1, b2...b13. It is a one-to-one correspondence.
  • each driving member 141 includes a shell body 1411 made of, for example, PP material, a push-pull rod 1412 located in the shell body 1411 , and a film 1413 made of, for example, soft rubber; the film 1413 is fixed to the shell body 1411 by, for example, double-sided tape. At the opening, one side is connected to the push-pull rod 1412, and the other side is connected to the elastic valve membrane 130.
  • the housing bodies 1411 of several driving members 141 can be used as a whole or separately, so that the number of driving members 141 can be increased or reduced as needed, and this disclosure does not limit this.
  • Each driving member 141 is used to control the opening or closing of a membrane valve.
  • the internal stress of the film 1413 is used to press the elastic valve membrane 130 against the liquid circuit valve plate 120, so that the membrane valve is in a normally closed state, and the push-pull rod 1412 is bonded on one side of the film 1413.
  • the film 1413 and its bonded elastic valve film 130 are separated from the liquid circuit valve plate 120, so that there is a gap between the liquid circuit valve plate 120 and the elastic valve film 130.
  • a gap is formed for liquid to pass through, so that the membrane valve can be opened, thereby connecting the corresponding reagent tube 111 and the pipetting channel 121 .
  • the driving member 141 in FIG. 5 is a driving member adapted to the membrane valve formed by the second preset area p2 and the liquid circuit valve plate 120. It is connected with the second preset area p2. The position of area p2 corresponds one to one.
  • the structures of the driving parts d1, d2, and d3 refer to the driving parts c1, c2...c13, and their working principles are also the same, so they will not be described again.
  • the pipetting channel 121 may be a pipe for liquid to pass through, and only the end of the pipe is the coverage area of the first preset area p1.
  • the end is set in an open structure, and a complete film is formed by covering the pipe. of pipelines.
  • the entire pipetting channel 121 is formed by a grooved coating.
  • the liquid circuit valve plate 120 is provided with a number of grooves, and the grooves are covered by the elastic valve membrane 130 to form a pipetting channel 121 .
  • the first preset area p1 covers part of the groove, so that when the membrane valve is opened, the reagent in the reagent tube 111 can be guided to the pipetting channel 121.
  • the pipetting channel 121 has a branch portion 1211 extending toward the valve hole b.
  • the branch portion 1211 is closer to the valve hole b.
  • the first preset area p1 When covering the valve hole b, only the branch portion 1211 is covered to lead the reagent to the pipetting channel 121 .
  • the liquid path valve plate 120 is also provided with a liquid outlet 123, such as a valve hole b16 and a liquid outlet channel 124.
  • a liquid outlet 123 such as a valve hole b16 and a liquid outlet channel 124.
  • One end of the liquid outlet channel 124 is connected to the liquid outlet.
  • 123 is in conduction, and the other end is in conduction with a valve hole, and is controlled by the membrane valve to achieve conduction or blocking with the pipetting channel 121, so that on the basis of liquid transfer between reagent tubes, the reagent tube 111 can also be
  • the liquid inside is led out from the liquid outlet 123 through the liquid outlet channel 124.
  • one of the membrane valves is used as the liquid outlet membrane valve, such as the membrane valve formed by the first preset area p1 covering the valve hole b15 and the pipetting channel 121 shown in Figure 3. It is located between a pipetting channel 121 and the outlet. Between the liquid channels 124, the passage is used to control the liquid outlet channel 124. By opening the liquid outlet film valve, the liquid in the reagent tube 111 can flow from the liquid outlet channel 124 to the liquid outlet 123.
  • the liquid outlet channel 124 can be a pipe provided on the liquid valve plate 120 for liquid to pass through, or it can be a complete pipe formed by being grooved and covered with a film.
  • the liquid outlet channel 124 is provided at the top of the liquid circuit valve plate 120, that is, on the opposite side of the valve film covering area p.
  • the liquid circuit valve plate 120 has a first coating area p4. After the first coating area p4 is coated, a complete Liquid outlet channel 124.
  • valve holes b15 and b16 When coating, one side of the valve holes b15 and b16 is covered, the other side of the valve hole b15 is covered by the elastic valve film 130, and the other side of the liquid outlet b16 can be connected to a liquid pipe 150 (see Figure 2) .
  • the first film covering area p4 and the valve film covering area p on both sides of the liquid line valve plate 120 respectively, and the liquid outlet channel 124 is arranged on the top of the liquid line valve plate 120, the liquid can flow from top to bottom to the liquid outlet. 123, to facilitate liquid transfer.
  • the liquid circuit valve plate 120 is also provided with at least one liquid receiving pipe 150 that is in communication with the liquid outlet 123.
  • the liquid valve plate 120 also includes a gas connector 125.
  • One end of the gas connector 125 is connected to an external air source, and the other end is connected to a valve hole, and
  • the membrane valve controls the connection or blocking of the pipetting channel 121 to clean the residual liquid in the pipetting channel 121 .
  • one of the membrane valves is used as a pipeline cleaning membrane valve, such as the membrane valve formed by the first preset area p1 covering the valve hole b14 and the part of the pipetting channel 121 shown in Figure 3, which is used to control the external air source.
  • a pipeline cleaning membrane valve such as the membrane valve formed by the first preset area p1 covering the valve hole b14 and the part of the pipetting channel 121 shown in Figure 3, which is used to control the external air source.
  • On and off open the pipeline cleaning membrane valve, and the gas enters the pipetting channel 121.
  • one of the reagent tubes 111 can be used as a waste liquid chamber. Just open the membrane valve of the waste liquid room at the same time, and the pipetting channel 121 can be The residual liquid in the reagent tube 111 is blown into the waste liquid chamber. After the residual liquid in the pipetting channel 121 is cleaned, the liquid in the next reagent tube 111 is transferred to avoid cross-contamination of the liquid.
  • the gas line joint 125 is a one-way valve, which is only used as an air inlet for the external air source.
  • the pipeline cleaning membrane valve is opened and the liquid is transferred to the liquid pipe 150, the gas channel in the gas line joint 125 is closed, and the liquid does not come into contact with the external environment, thereby preventing aerosol cross-infection, and the liquid transfer device 100 remains in a fully enclosed environment.
  • the liquid line valve plate 120 is also provided with a quantitative tank 126 for quantitative transfer of liquid.
  • the quantitative cell 126 can be disposed between two adjacent reagent tubes 111 and located in the pipetting channel 121 .
  • the reagent tube 111 can be composed of hard plastic and film.
  • the tube body of the hard plastic can be cut along the axial direction, And cover the axial section with film, such as PE, PVC film, TPU film, so that after the membrane valve is opened by external force, negative pressure is provided by operating the piston push rod 112 in the reagent tubes 09 and 010, and the force of the film's contraction is used to
  • the reagents in reagent tubes 01-08 and 012 are squeezed out to better discharge the reagents.
  • the hard plastic can have at least one axial section, for example two, and be coated with films respectively to ensure sealing, and this disclosure does not limit this.
  • the reagent tubes 01-08 and 012 have a liquid inlet end and a liquid outlet end.
  • the liquid outlet end is connected to the valve hole b.
  • the liquid inlet end is configured to be closed. end to ensure that the reagents are in a sealed environment.
  • the liquid inlet end can be sealed with a film or sealed with a sealing plug, which is not limited by this disclosure.
  • the traditional manual nucleic acid detection method has a complex operation process and low degree of automation, and cross-contamination is prone to occur when samples are tested or transferred; while existing automated detection equipment requires multiple devices to work together, and the samples after the previous steps are completed It needs to be transferred to subsequent equipment, which is cumbersome and time-consuming. During the sample transfer process, it is also easily contaminated by the external environment or contaminates the detection environment. The transfer and detection throughput and detection efficiency are low.
  • the liquid transfer device of the present disclosure realizes the transfer of liquid between multiple reagent tubes by controlling the opening of the membrane valve.
  • Samples, extracted reagents, etc. can be placed in the reagent tubes in advance and the reagent tubes are sealed to form a sealed environment, thereby ensuring Liquid transfer can be completed in an environment without contact with the outside world, avoiding possible contamination of samples and improving sample detection accuracy.
  • nucleic acid extraction by magnetic beads needs to be explained. After the sample is added to the lysis solution, the nucleic acids are released, and then treated magnetic beads (such as silicon-based or amino-coated) are used to "specifically bind" the nucleic acids. ", forming a "nucleic acid-magnetic bead complex", and then the complex is separated under the action of an external magnetic field. Finally, the non-specific adsorbed impurities are washed away with the eluent, desalted, and purified, and the desired extract is obtained. Nucleic acid substances.
  • treated magnetic beads such as silicon-based or amino-coated
  • the reagent tubes 01-013 are: waste liquid chamber 01, sample chamber 02, lysis chamber 03, empty chamber 04, washing liquid chamber 05, washing liquid chamber Two 06, eluent chamber 07, magnetic elution chamber 08, mixing tube one 09, mixing tube two 010, mineral oil chamber 011, excess chamber 012, secondary sample addition chamber 013; among them, waste liquid chamber 01, sample Chamber 02, lysis chamber 03, empty chamber 04, washing liquid chamber 1 05, washing liquid chamber 2 06, and eluent chamber 07 are respectively connected to their respective valve holes b1, b2...b7, and are connected through the driving parts c1, c2 ...
  • the control of c7 realizes liquid transfer in a pipetting channel 121; the magnetic elution chamber 08, mixing tube one 09, and mixing tube two 010 are respectively connected to their respective valve holes b8, b9, and b10, and are driven by the driving member
  • Liquid transfer is realized in the liquid channel 121; the secondary sampling chamber 013 is connected to the valve hole b13, and is directly connected to the liquid outlet channel 124 under the control of the driving member c13.
  • the two pipetting channels 121 are connected to each other by the control of the driving parts d1, d2, and d3 respectively.
  • the liquid circuit valve plate 120 is also provided with a quantitative tank 126, which is located in the pipetting channel 121 between the mineral oil chamber 011 and the excess chamber 012.
  • the first pipetting channel is used for liquids in the waste liquid chamber 01, the sample chamber 02, the lysis chamber 03, the empty chamber 04, the washing liquid chamber 105, the washing liquid chamber 206, and the elution liquid chamber 07.
  • the second pipetting channel is used for liquid transfer in magnetic elution chamber 08, mixing tube one 09, mixing tube two 010, the third pipetting channel is used for liquid transfer in mineral oil chamber 011, excess chamber 012, the fourth pipetting channel
  • the pipetting channel is used for liquid transfer in the secondary loading chamber 013.
  • the elastic valve membrane 130 has three second preset areas P2, and three membrane valves are formed between the three second preset areas P2 and the liquid circuit valve plate 120, respectively used to conduct or block the adjacent first displacement areas. a liquid channel and a second pipetting channel, an adjacent second pipetting channel and a third pipetting channel, and an adjacent third pipetting channel and a fourth pipetting channel.
  • Reagent packaging Place the sample (such as nucleic acid sample), lysis solution, magnetic bead preservation solution, washing solution, eluent, and mineral oil into the corresponding reagent tubes, for example, put the sample into sample chamber 02 and the lysis solution into Lysis chamber 03, place the wash solution in wash solution chamber 1 05, wash solution chamber 2 06, place the eluent in the eluent chamber 07, place the magnetic bead preservation solution in the magnetic elution chamber 08, place mineral oil in the mineral Oil chamber 011, then seal the above-mentioned reagent tube, and build a piston push rod 112 in the mixing tube one 09, the mixing tube two 010, the mineral oil chamber 011, and the secondary sample addition chamber 013;
  • Magnetic bead activation Open the membrane valve corresponding to the magnetic elution chamber 08 and the mixing tube 109, operate the piston push rod 112 built in the mixing tube 1 to reciprocate, activate the magnetic beads, and then apply it outside the magnetic elution chamber 08
  • the permanent magnet magnetically attracts the magnetic beads, and pumps the magnetic bead activation solution into the mixing tube 09; after that, open the membrane valve corresponding to the empty chamber 04, the first pipetting channel and the second pipetting channel, and close the magnetic elution
  • Pipeline cleaning Open the waste chamber 01, the membrane valve corresponding to the first pipetting channel and the second pipetting channel, the membrane valve corresponding to the second pipetting channel and the third pipetting channel, the third pipetting channel and the fourth pipetting channel.
  • the membrane valve corresponding to the pipetting channel and the pipeline cleaning membrane valve corresponding to the air line connector 125, the external air source inlet blows the residual liquid in the liquid line into the waste liquid chamber 01;
  • the sample is lysed to release nucleic acid: open the membrane valve corresponding to the sample chamber 02 and the mixing tube 109, operate the piston push rod 112 built into the mixing tube 109, and transfer the sample to the mixing tube 109. In the same way, transfer the lysis solution to the mixing tube 112. In tube two 010, close the membrane valve corresponding to the first pipetting channel and the second pipetting channel; then remove the magnetic beads from the magnetic field, and push the sample to the magnetic elution chamber 08 through the piston rod built in mixing tube one 09.
  • Nucleic acid extraction and transfer transfer the mixed solution after sample lysis to the magnetic elution chamber 08, operate the piston pusher 112 built into the mixing tube one 09 and the mixing tube two 010, and remove the wash solution, eluent, and sample after lysis.
  • the mixed solution is repeatedly transferred in the magnetic elution chamber 08, mixing tube 1 09, and mixing tube 2 010 for nucleic acid extraction.
  • the above pipeline cleaning steps can be repeated to avoid cross-contamination of reagents, and the waste liquid is discharged into the corresponding into the reagent tube, and then push the excess portion of the extracted nucleic acid solution into the excess chamber 012 through the quantitative cell 126, and then move the quantitative nucleic acid solution out to the liquid receiving pipe 150 by operating the piston pusher 112 built into the mineral oil chamber 011 middle;
  • Secondary adding operate the piston push rod 112 built into the secondary adding chamber 013 to add secondary reagents (usually low-temperature reagents that are difficult to pre-place in the reagent tube 111) into the liquid receiving tube 150, and then prepare for subsequent PCR amplification process.
  • secondary reagents usually low-temperature reagents that are difficult to pre-place in the reagent tube 11
  • an embodiment of the present disclosure also provides a multi-channel parallel liquid transfer device, each channel including the liquid transfer device in the embodiment shown in FIGS. 1-6 . Specific technical details can be found above and will not be repeated here.
  • the multi-channel parallel liquid transfer device provided by the embodiments of the present disclosure can always ensure a fully enclosed state during liquid transfer.
  • the reaction process does not need to be in contact with atmospheric air, and can be carried out in non-negative pressure biological experimental environments such as homes, communities, and outdoors. Transfer and detection will not cause cross-infection caused by aerosols; and through the multi-channel integrated structure, liquid samples can be transferred and tested separately in each channel, and multiple channels of different individual samples can also be transferred and tested simultaneously, automatically. The degree is high, and the transfer and detection throughput as well as the transfer and detection efficiency are improved.

Abstract

一种液体转移装置（100）及多路并联的液体转移装置，液体转移装置（100）包括：液路阀板（120），底部具有阀膜覆盖区域（P），阀膜覆盖区域（P）设置有至少一条移液通道（121）、若干阀孔（b）；阀孔（b）与移液通道（121）之间具有第一预设距离；卡盒本体（110），固定于液路阀板（120）的顶部，卡盒本体（110）包括若干试剂管（111），每一试剂管（111）与一个阀孔（b）导通；弹性阀膜（130），覆盖于阀膜覆盖区域（P）；弹性阀膜（130）具有若干第一预设区域（P1），第一预设区域（P1）与液路阀板（120）之间形成若干个膜阀，用于导通或者阻断阀孔（b）和移液通道（121）；驱动组件（140），用于开启或者关闭膜阀。多路并联的液体转移装置的每一路包括液体转移装置（100）。

Description

液体转移装置及多路并联的液体转移装置
相关申请的交叉引用
无。
技术领域
本公开涉及生物医药仪器技术领域，具体涉及一种液体转移装置及多路并联的液体转移装置。
背景技术
在生物、化学、食品、医药、防疫或环境监测等领域的生产、试验或检测过程中，通常都会涉及到气体或液体试剂的转移，而有些液体化学试剂，如乙醚、苯酚等易挥发且有毒的药品；或者，有些容易引起感染、过敏、肿瘤等疾病的微生物病原体，如病毒、细菌、立克次体、支原体、衣原体、螺旋体、真菌、放线菌等，在转移过程中，大多数采用的是开放式的吸取、转移装置，或者试剂瓶之间的倾倒等方式，如此，在试剂的转移过程中不能做到密闭操作，因此容易导致易挥发的有毒试剂挥发扩散到容器外部，污染外部环境，并且会危及操作人员的人身安全。
近年来出现的SARS、高致病性禽流感、新型冠状病毒等疾病的传染性强，因此对病原体的转移及检测必须做到安全、快速和准确。例如，核酸检测具有灵敏度高、特异性好的特点，在疾病诊断、疫情防控、健康监测等领域具有重要的应用。在现阶段的核酸检测技术中，主要包含以下两种检测形式：
第一种是传统的人工检测，通过人为操作移液枪重复在PCR反应试管中添加各种生化反应试剂，并转移样本。该方法需要在负压条件下完成，依赖专业检测人员的手工操作，而且样本存储、提取或转移过程中通常使用如玻璃等材质的刚性试剂管，样品提取或转移不便，而且操作过程复杂、自动化程度不高，样本在检测或转移时容易出现交叉污染，导致结果出现假阳等一系列问题；并且在开放性环境下检测人员容易增加感染病毒的概率。
第二种是自动化的检测设备，目前市场上的核酸自动检测设备在核酸提取、扩增和检测步骤中大多数是采用独立的方式进行，即每个步骤都需要独立的设备完成，一次核酸检测过程中需要多台设备操作。一方面，多台设备占用空间较大，另一方面，前序步骤完成后的样品需转移到后续的设备中，操作繁琐，耗时较长，并且现有的核酸检测设备大多是通过电磁阀的形式来控制液体转移，采用电磁阀的形式，阀芯与试剂有接触，而且阀芯需要运动，必然会产生一定的间隙，因此试剂会有泄露的风险，在样品转移过程中也容易受到外部环境的污染或污染检测环境。
另外，目前商品化的核酸检测设备也陆续出现了集提取、扩增和检测于一体的全自动核酸检测设备，但是它们绝大部分采用的是单通道或单液体转移和检测的方式，即检测设备一次只能提取一种样品针对单个病原体进行检测，如Cepheid公司的GeneXpert、生物梅里埃公司的FilmArray等，上述产品的检测通量和效率均较低。
发明内容
为了解决相关技术中的问题，本公开实施例提供一种液体转移装置及多路并联的液体转移装置。
第一方面，本公开实施例提供了一种液体转移装置。
具体地，所述液体转移装置，包括：
液路阀板，底部具有阀膜覆盖区域，所述阀膜覆盖区域设置有至少一条移液通道、若干阀孔；所述阀孔与所述移液通道之间具有第一预设距离；
卡盒本体，固定于所述液路阀板的顶部，所述卡盒本体包括若干试剂管，每一试剂管与一个所述阀孔导通；
弹性阀膜，覆盖于所述阀膜覆盖区域；所述弹性阀膜具有若干第一预设区域，所述第一预设区域与所述液路阀板之间形成若干个膜阀，用于导通或者阻断所述阀孔和所述移液通道；
驱动组件，用于开启或者关闭所述膜阀。
可选地，所述液路阀板上设置有若干刻槽，所述刻槽为所述弹性阀膜覆盖形成所述移液通道。
可选地，所述移液通道具有向所述阀孔延伸的支路部分。
可选地，所述弹性阀膜还具有若干第二预设区域；所述第二预设区域与所述液路阀板之间形成若干个所述膜阀，用于导通或者阻断相邻两条移液通道；其中，所述相邻两条移液通道之间具有第二预设距离。
可选地，所述驱动组件包括：若干驱动件；
每一驱动件包括：壳本体、位于所述壳本体内的推拉杆以及胶片；所述胶片固定于所述壳本体的开口处，一面与所述推拉杆连接，另一面与所述弹性阀膜连接。
可选地，所述弹性阀膜以一体或分体的形式铺设在所述液路阀板上。
可选地，所述液路阀板上还设置有出液口、出液通道；
所述出液通道一端与所述出液口导通，另一端与一个所述阀孔导通，并由所述膜阀控制实现与所述移液通道的导通或者阻断。
可选地，所述液路阀板的顶部具有第一覆膜区域；所述第一覆膜区域设置有所述出液通道。
可选地，所述液路阀板还设置至少一个接液管；所述接液管与所述出液口导通。
可选地，所述液路阀板还设置气路接头；所述气路接头与一个所述阀孔导通，并由所述膜阀控制实现与所述移液通道的导通或者阻断。
可选地，所述液路阀板还设置定量池，设置在两个相邻的所述试剂管之间，且位于所述移液通道内。
可选地，部分所述试剂管内置活塞推杆。
可选地，所述试剂管为密封腔室，包括依次设置的废液室、样本室、裂解室、空室、洗液室、洗脱液室、磁吸洗脱室、混合管、矿物油室、过量室、二次加样室。
可选地，所述密封腔室通过密封件进行密封，所述密封件选自覆膜或活塞。
可选地，所述移液通道为四条，第一移液通道用于所述废液室、样本室、裂解室、空室、 洗液室、洗脱液室的液体转移，第二移液通道用于所述磁吸洗脱室、混合管的液体转移，第三移液通道用于所述矿物油室、过量室的液体转移，第四移液通道用于所述二次加样室的液体转移。
可选地，所述液路阀板还设置定量池，位于所述矿物油室、过量室之间的所述移液通道内。
可选地，所述弹性阀膜还具有三个第二预设区域；所述第二预设区域与所述液路阀板之间形成三个所述膜阀，分别用于导通或者阻断相邻的所述第一移液通道与第二移液通道，相邻的所述第二移液通道与第三移液通道，以及相邻的所述第三移液通道与第四移液通道。
第二方面，本公开实施例提供了一种多路并联的液体转移装置。
具体地，所述多路并联的液体转移装置中，每一路包括如第一方面任一项所述的液体转移装置。
本公开实施例提供的技术方案可以包括以下有益效果：
本公开提供的液体转移装置，包括：液路阀板，底部具有阀膜覆盖区域，所述阀膜覆盖区域设置有至少一条移液通道、若干阀孔；所述阀孔与所述移液通道之间具有第一预设距离；卡盒本体，固定于所述液路阀板的顶部，所述卡盒本体包括若干试剂管，每一试剂管与一个所述阀孔导通；弹性阀膜，覆盖于所述阀膜覆盖区域；所述弹性阀膜具有若干第一预设区域，所述第一预设区域与所述液路阀板之间形成若干个膜阀，用于导通或者阻断所述阀孔和所述移液通道；驱动组件，用于开启或者关闭所述膜阀。本公开的样本转移过程在全封闭状态下进行，可以非负压生物实验环境中进行液体试剂的转移及检测，避免造成气溶胶引起交叉感染的风险；试剂预先装于所述试剂管中，通过驱动组件控制弹性膜阀向试剂管方向运动，关闭膜阀，使弹性膜阀紧贴试剂管流体出口，将试剂管中试剂封装于试剂管中；使用时驱动组件控制弹性膜阀向试剂管相反的方向运动，打开膜阀，使弹性膜阀与试剂管出口产生空隙，将试剂管中的试剂释放至液路阀板的移液通道中。膜阀打开的状态下，通过与试剂管中预设置的推杆配合，可实现流体在试剂管间的快速转移和混匀。而且通过将多个液体转移装置并联，既可以在每一路单独进行液体样本的转移和检测，也可以实现多路不同个体样本的同时转移和检测，自动化程度高，并且提升了转移和检测通量以及转移和检测效率。
应当理解的是，以上的一般描述和后文的细节描述仅是示例性和解释性的，并不能限制本公开。
附图说明
为了更清楚地说明本公开实施例或相关技术中的技术方案，下面将对示例性实施例或相关技术描述中所需要使用的附图作一简单地介绍，显而易见地，下面描述中的附图是本公开的一些示例性实施例，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示出根据本公开实施例的液体转移装置的立体图。
图2示出根据本公开实施例的液体转移装置的爆炸图。
图3示出根据本公开实施例的卡盒本体与液路阀板的位置关系示意图。
图4示出根据本公开实施例的弹性阀膜与液路阀板的位置关系示意图。
图5示出根据本公开实施例的驱动组件与液路阀板的位置关系示意图。
图6示出根据本公开实施例的驱动组件的结构示意图。
具体实施方式
下文中，将参考附图详细描述本公开的示例性实施例，以使本领域技术人员可容易地实现它们。此外，为了清楚起见，在附图中省略了与描述示例性实施例无关的部分。
此外，本领域普通技术人员应当理解，在此提供的附图都是为了说明的目的，并且附图不一定是按比例绘制的。
除非上下文明确要求，否则在说明书的“包括”、“包含”等类似词语应当解释为包含的含义而不是排他或穷举的含义；也就是说，是“包括但不限于”的含义。
在本公开的描述中，需要理解的是，术语“第一”、“第二”等仅用于描述目的，而不能理解为指示或暗示相对重要性。此外，在本公开的描述中，除非另有说明，“多个”的含义是两个或两个以上。
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公开中的具体含义。
另外还需要说明的是，在不冲突的情况下，本公开中的实施例及实施例中的特征可以相互组合。下面将参考附图并结合实施例来详细说明本公开。
为至少部分地解决发明人发现的现有技术中的问题而提出本公开。
如图1至图6所示，液体转移装置100包括：卡盒本体110、液路阀板120、弹性阀膜130、驱动组件140。卡盒本体110位于液路阀板120的顶部，卡盒本体110与液路阀板120可以一体成型或者组装为一体使用，液路阀板120的底部具有阀膜覆盖区域P，弹性阀膜130例如通过键合方式覆盖于阀膜覆盖区域P上，驱动组件140位于弹性阀膜130的下方，例如通过超声焊接方式与弹性阀膜130连接。
卡盒本体110包括若干个试剂管111，若干个试剂管111固定于液路阀板120的顶部，图中示出了两种类型的试剂管111，即试剂管01、02、03、04、05、06、07、08、012以及试剂管09、010、011、013，其中，试剂管09、10、011、013内置活塞推杆112(参见图2)，试剂管01-08、012被配置为密封腔室。在后文的实施例中，申请人将结合磁珠法提取核酸的应用场景进一步进行说明，在此不予赘述。
液路阀板120上设置有与试剂管111数量适配的阀孔b，即阀孔b1、b2、b3、……、b13，每一阀孔b与一个试剂管111导通。例如，阀孔b1与试剂管01导通，阀孔b2与试剂管02导通等等。
液路阀板120的阀膜覆盖区域p内设置有至少一条移液通道121，移液通道121与阀孔b 具有第一预设距离，弹性阀膜130上具有若干个第一预设区域P1，当弹性阀膜130覆盖于阀膜覆盖区域p时，若干个第一预设区域P1与液路阀板120之间形成若干个膜阀，在膜阀关闭时，移液通道121与阀孔b的间隙为弹性阀膜130阻断，因此二者无法导通，预先配置在试剂管111的液体试剂无法由阀孔b流入移液通道121内，在膜阀开启时，第一预设区域P1与液路阀板120之间形成导通移液通道121与阀孔b的间隙，预先配置在试剂管111的液体试剂由阀孔b流经该间隙并流入移液通道121内。驱动组件140提供开启或者关闭膜阀的作用力，通过开启两个或多个试剂管111对应的膜阀，多个试剂管111可以经由移液通道121实现液体转移。
在本公开的实施例中，例如图4所示，第一预设区域p1同时覆盖阀孔b和部分移液通道121，第一预设区域p1外的部分例如图中阴影部分焊接于阀膜覆盖区域p上，从而保证在外力作用下仅第一预设区域p1与液路阀板120之间形成间隙，试剂管111内的液体不会从弹性阀膜130的边沿泄露。
在本公开的实施例中，弹性阀膜130还具有第二预设区域p2，第二预设区域p2与液路阀板120之间形成若干个膜阀，用于导通或者阻断相邻两条移液通道；其中，相邻两条移液通道之间具有第二预设距离。
具体地，第二预设区域p2覆盖于液路阀板120上的区域为p3区域，弹性阀膜130覆盖于p3区域时，若干个第二预设区域p2与液路阀板120之间形成若干个膜阀，相邻两条移液通道121的端部位于p3区域，这两条移液通道121之间并不导通，在膜阀关闭时，相邻两条移液通道121的间隙为弹性阀膜130阻断，即试剂管111内的液体无法经两条移液通道121进行转移，例如试剂管07、08之间无法进行液体转移，在膜阀开启时，第二预设区域P2与液路阀板120之间形成导通相邻两条移液通道121的间隙，例如导通试剂管07、08所在的移液通道的间隙，试剂管07内液体可经由间隙流向试剂管08，这样试剂管111就根据对应的移液流道121被划分为不同的功能区域，同一功能区域内可以经由一条共用的移液通道121进行液体转移，不同功能区域之间经由第二预设区域p2与液路阀板120之间形成的膜阀的控制实现液体转移。
进一步地，例如图4所示，当弹性阀膜130上具有多个第二预设区域p2，而相邻两个功能区域之间进行液体转移，无需其他功能区域的试剂管111参与液体转移时，可以通过关闭相应功能区域的第二预设区域的膜阀来切断与其他功能区域的通路，避免对发生液体转移对其他功能区域的影响。例如，试剂管07、08间进行液体转移时，可以开启导通试剂管07、08所在移液通道第二预设区域的膜阀，而关闭试剂管b10、b11所在移液通道第二预设区域的膜阀，换句话说，试剂管b11、b12之间的液体转移也可以独立进行，而不受试剂管07、08间液体转移的影响。
在本公开的实施例中，弹性阀膜130以一体或分体的形式铺设在所述液路阀板120上形成若干个膜阀。
在本公开的实施例中，例如图5所示，驱动组件140包括若干驱动件141，例如驱动件c1、c2……c13，驱动件c1、c2……c13与阀孔b1、b2……b13是一一对应的关系。
例如图6所示，每一个驱动件141包括例如PP材质的壳本体1411、位于壳本体1411内的推拉杆1412以及例如软胶材质的胶片1413；胶片1413例如通过双面胶固定于壳本体1411的 开口处，一面与推拉杆1412连接，另一面与弹性阀膜130连接。其中，若干个驱动件141的壳本体1411即可以作为一个整体，也可以分体设置，从而根据需要增加或者减少驱动件141的数量，本公开对此不做限制。
每一驱动件141用于控制一个膜阀的开启或者关闭，具体地，利用胶片1413的内应力将弹性阀膜130贴紧液路阀板120上，从而使得膜阀处于常闭状态，推拉杆1412粘接在胶片1413的一侧，通过向外拉动推拉杆1412，胶片1413随同其粘接的弹性阀膜130与液路阀板120分离，从而在液路阀板120与弹性阀膜130之间形成供液体通过的间隙，实现膜阀的开启，进而导通相应的试剂管111与移液通道121。
需要注意的是，图5中驱动件141，例如驱动件d1、d2、d3，是适配第二预设区域p2与液路阀板120形成的膜阀的驱动件，其与第二预设区域p2的位置一一对应。驱动件d1、d2、d3的结构参照驱动件c1、c2……c13，其作用原理也相同，在于不予赘述。
可以理解，图1-6示出的试剂管、阀孔、驱动件的数量仅是示意性的，本领域技术人员可以根据需要灵活进行调整，并不构成对本公开的限制。
在本公开的实施例中，移液通道121可以是供液体通过的管道，仅管道的端部为第一预设区域p1的覆盖区域，例如端部设置为开口构造，而通过覆膜形成完整的管道。或者，移液通道121整体是由刻槽覆膜形成。具体地，液路阀板120上设置有若干刻槽，刻槽为弹性阀膜130覆盖形成移液通道121。其中，第一预设区域p1覆盖部分刻槽，从而当膜阀开启时，试剂管111内的试剂可以导出至移液通道121。
在本公开的实施例中，例如图4所示，移液通道121具有向阀孔b延伸的支路部分1211，该支路部分1211与阀孔b的距离更近，第一预设区域p1覆盖阀孔b时，只需覆盖支路部分1211就可以实现将试剂导出至移液通道121。
在本公开的实施例中，例如图2、图3所示，液路阀板120上还设置有出液口123，例如阀孔b16、出液通道124，出液通道124一端与出液口123导通，另一端与一个阀孔导通，并由膜阀控制实现与移液通道121的导通或者阻断，从而在试剂管之间进行液体转移的基础上，还能够将试剂管111内的液体通过出液通道124从出液口123导出。
具体地，其中一个膜阀作为出液膜阀，例如图3所示的由第一预设区域p1覆盖阀孔b15、移液通道121的部分形成的膜阀，位于一条移液通道121与出液通道124之间，用于控制出液通道124的通路，打开出液膜阀，试剂管111内的液体可以从出液通道124流向出液口123。
在本公开的实施例中，出液通道124可以是设置在液路阀板120上的供液体通过的管道，也可以是刻槽经覆膜形成的完整管道，例如图3所示，出液通道124设置在液路阀板120的顶部，即阀膜覆盖区域p的相对一侧，液路阀板120上具有第一覆膜区域p4，在第一覆膜区域p4覆膜后形成完整的出液通道124。在覆膜时，将阀孔b15、b16的一侧覆盖，阀孔b15的另一侧由弹性阀膜130覆盖，出液口b16的另一侧可以连接一接液管150(参见图2)。通过将第一覆膜区域p4与阀膜覆盖区域p分别设置在液路阀板120的两侧，出液通道124设置在液路阀板120的顶部，液体可以从上向下流向出液口123，便于液体转移。
在本公开的实施例中，例如图2所示，液路阀板120还设置至少一个接液管150，与出液 口123导通。
在本公开的实施例中，例如图2、图3所示，液路阀板120还包括气路接头125，气路接头125一端与外部气源连接，另一端与一个阀孔导通，并由膜阀控制实现与移液通道121的导通或者阻断，用于清理移液通道121内的残留液体。
具体地，其中一个膜阀作为管路清洁膜阀，例如图3所示的由第一预设区域p1覆盖阀孔b14、移液通道121的部分形成的膜阀，用于控制外部气源的通断，打开管路清洁膜阀，气体进入移液通道121，此时可以将试剂管111中的一个作为废液室，只需同时打开废液室的膜阀，就可以将移液通道121内的残留液体吹入废液室中，待移液通道121的残留液体清理后，再进行下一个试剂管111内的液体转移，避免了液体的交叉污染。
需要说明的是，气路接头125选取单向阀，仅作为外部气源的进气口，当打开管路清洁膜阀，将液体转移至接液管150时，气路接头125内的气体通道是关闭的，液体并不与外部环境接触，从而不会造成气溶胶的交叉感染，液体转移装置100仍保持为全封闭环境。
在本公开的实施例中，例如图4所示，液路阀板120还设置定量池126，用于定量转移液体。具体地，定量池126可以设置在两个相邻的试剂管111之间，且位于移液通道121内。
在本公开的实施例中，试剂管111，例如图3中的试剂管01-08、012可以由硬质塑料和薄膜组成，具体地，可以将硬质塑料的管本体沿轴向剖开，并在轴向剖面覆膜，例如PE、PVC薄膜、TPU薄膜，从而在外力开启膜阀后，通过操作试剂管09、010内的活塞推杆112提供负压，利用薄膜内缩的作用力将试剂管01-08、012中的试剂向外挤出，能更好地排出试剂。可以理解，硬质塑料可以至少具有一个轴向剖面，例如两个，并分别覆膜，以保证密封性，本公开对此不做限制。
在本公开的实施例中，试剂管01-08、012具有进液端和出液端，出液端与阀孔b导通，在进液端置入试剂后，进液端被配置为封闭端，以保证试剂处于密封环境。具体地，可以在进液端覆膜密封，或者利用密封塞密封，本公开对此不做限制。
前文提及，传统的人工核酸检测方法操作过程复杂、自动化程度不高，样本在检测或转移时容易出现交叉污染；而已有的自动化检测设备需要多台设备协同作业，前序步骤完成后的样品需转移到后续的设备中，操作繁琐，耗时较长，并且在样品转移过程中也容易受到外部环境的污染或污染检测环境，转移及检测通量以及检测效率较低。
本公开的液体转移装置，通过控制膜阀的开启实现液体在多个试剂管之间的转移，试剂管中可以预先置入样本、提取试剂等并将试剂管密封，形成密封环境，从而保证了液体转移可以在不与外界接触的环境中完成，避免了样本可能收到的污染，提高了样本检测精度。
下面的实施例，以磁珠法提取核酸进行示意性说明。
首先需要对磁珠法提取核酸的原理进行说明，样本加入裂解液后，核酸被释放出来，然后利用经处理过的磁珠(例如经硅基、氨基包被处理)与核酸进行“特异性结合”，形成"核酸-磁珠复合物"，之后在外加磁场的作用下，将复合物分离出来，最后经过洗脱液洗去非特异性吸附的杂质、去盐、纯化后，即得到欲提取的核酸物质。
本公开的液体转移装置中，例如图3-5所示，试剂管01-013分别是：废液室01、样本室 02、裂解室03、空室04、洗液室一05、洗液室二06、洗脱液室07、磁吸洗脱室08、混合管一09、混合管二010、矿物油室011、过量室012、二次加样室013；其中，废液室01、样本室02、裂解室03、空室04、洗液室一05、洗液室二06、洗脱液室07分别与各自的阀孔b1、b2……b7导通，并经驱动件c1、c2……c7的控制在一条移液通道121内实现液体转移；磁吸洗脱室08、混合管一09、混合管二010分别与各自的阀孔b8、b9、b10导通，并经驱动件c8、c8、c9的控制在一条移液通道121内实现液体转移；矿物油室011、过量室012分别与各自的阀孔b11、b12导通，并经驱动件c11、c12的控制在一条移液通道121内实现液体转移；二次加样室013与阀孔b13导通，经驱动件c13的控制直接与出液通道124导通。其中，两条移液通道121之间分别由驱动件d1、d2、d3的控制实现导通。液路阀板120还设置定量池126，位于矿物油室011、过量室012之间的移液通道121内。
移液通道121为四条，第一移液通道用于废液室01、样本室02、裂解室03、空室04、洗液室一05、洗液室二06、洗脱液室07的液体转移，第二移液通道用于磁吸洗脱室08、混合管一09、混合管二010的液体转移，第三移液通道用于矿物油室011、过量室012的液体转移，第四移液通道用于二次加样室013的液体转移。
弹性阀膜130具有三个第二预设区域P2，三个第二预设区域P2与液路阀板120之间形成三个膜阀，分别用于导通或者阻断相邻的第一移液通道与第二移液通道，相邻的第二移液通道与第三移液通道，以及相邻的第三移液通道与第四移液通道。
利用本公开实施例提供的液体转移装置进行PCR核酸提取，包括如下步骤：
试剂封装：将样本(如核酸试样)以及裂解液、磁珠保存液、洗液、洗脱液、矿物油分别置入相应的试剂管中，例如样本置入样本室02、裂解液置入裂解室03、洗液分别置入洗液室一05、洗液室二06、洗脱液置入洗脱液室07、磁珠保存液置入磁吸洗脱室08、矿物油置入矿物油室011，然后密封上述试剂管，并在混合管一09、混合管二010、矿物油室011、二次加样室013内置活塞推杆112；
磁珠活化：打开磁吸洗脱室08、混合管一09对应的膜阀，操作混合管一内置的活塞推杆112往复移动，对磁珠进行活化，然后在磁吸洗脱室08外施加永磁铁对磁珠进行磁吸，将磁珠活化液抽到混合管一09内；之后，打开空室04、第一移液通道与第二移液通道对应的膜阀，关闭磁吸洗脱室08对应的膜阀，操作活塞推杆112，将废液转移至空室04内，然后关闭空室04对应的膜阀；
管路清洗：打开废液室01、第一移液通道与第二移液通道对应的膜阀、第二移液通道与第三移液通道对应的膜阀、第三移液通道与第四移液通道对应的膜阀、以及气路接头125对应的管路清洁膜阀，外部气源进气将液路里的残留液体吹入废液室01内；
样本裂解释放核酸：打开样本室02、混合管一09对应的膜阀，操作混合管一09内置的活塞推杆112，将样本转移至混合管一09内，同理，将裂解液转移至混合管二010内，关闭第一移液通道与第二移液通道对应的膜阀；然后将磁珠脱离磁场，并通过混合管一09内置的活塞杆将样本推至磁吸洗脱室08，操作混合管一09内置的活塞推杆112往复运动，将样本携带磁珠转移至混合管一09内；之后操作混合管一、混合管二内置的活塞推杆112，将样本和裂解液 混合、裂解样本释放核酸；
核酸提取、转移：将样本裂解后的混合溶液转移至磁吸洗脱室08，操作混合管一09、混合管二010内置的活塞推杆112，将洗液、洗脱液、以及样本裂解后的混合溶液在磁吸洗脱室08、混合管一09、混合管二010反复转移进行核酸提取，提取过程中可以重复上述管路清洗的步骤以避免试剂的交叉污染，废液则排入相应的试剂管内，之后将提取到的核酸溶液经定量池126将过量部分推入过量室012中，再通过操作矿物油室011内置的活塞推杆112将定量后的核酸溶液移出至接液管150中；
二次加样：操作二次加样室013内置的活塞推杆112，可以向接液管150中加入二次试剂(通常是低温，不易预先置入试剂管111中的试剂)，然后准备后续的PCR扩增过程。
根据本公开的实施例，本公开实施例还提供一种多路并联的液体转移装置，每一路包括如图1-图6所示的实施例中的液体转移装置。具体的技术细节可以参见上文，在此不予赘述。
本公开实施例提供的多路并联的液体转移装置，在液体转移时始终能够保证在全封闭状态，反应过程无需与大气空气接触，可以实现家庭、社区、户外等非负压生物实验环境中进行转移和检测，不会造成气溶胶引起交叉感染；而且通过多路一体式结构，既可以在每一路单独进行液体样本的转移和检测，也可以实现多路不同个体样本的同时转移和检测，自动化程度高，并且提升了转移和检测通量以及转移和检测效率。
以上描述仅为本公开的较佳实施例以及对所运用技术原理的说明。本领域技术人员应当理解，本公开中所涉及的发明范围，并不限于上述技术特征的特定组合而成的技术方案，同时也应涵盖在不脱离所述发明构思的情况下，由上述技术特征或其等同特征进行任意组合而形成的其它技术方案。例如上述特征与本公开中公开的(但不限于)具有类似功能的技术特征进行互相替换而形成的技术方案。

Claims (18)

  1. 一种液体转移装置，其特征在于，包括：
    液路阀板，底部具有阀膜覆盖区域，所述阀膜覆盖区域设置有至少一条移液通道、若干阀孔；所述阀孔与所述移液通道之间具有第一预设距离；
    卡盒本体，固定于所述液路阀板的顶部，所述卡盒本体包括若干试剂管，每一试剂管与一个所述阀孔导通；
    弹性阀膜，覆盖于所述阀膜覆盖区域；所述弹性阀膜具有若干第一预设区域，所述第一预设区域与所述液路阀板之间形成若干个膜阀，用于导通或者阻断所述阀孔和所述移液通道；
    驱动组件，用于开启或者关闭所述膜阀。
  2. 根据权利要求1所述的液体转移装置，其特征在于，
    所述液路阀板上设置有若干刻槽，所述刻槽为所述弹性阀膜覆盖形成所述移液通道。
  3. 根据权利要求2所述的液体转移装置，其特征在于，
    所述移液通道具有向所述阀孔延伸的支路部分。
  4. 根据权利要求1所述的液体转移装置，其特征在于，
    所述弹性阀膜还具有若干第二预设区域；所述第二预设区域与所述液路阀板之间形成若干个所述膜阀，用于导通或者阻断相邻两条移液通道；其中，所述相邻两条移液通道之间具有第二预设距离。
  5. 根据权利要求4所述的液体转移装置，其特征在于，
    所述驱动组件包括：若干驱动件；
    每一驱动件包括：壳本体、位于所述壳本体内的推拉杆以及胶片；所述胶片固定于所述壳本体的开口处，一面与所述推拉杆连接，另一面与所述弹性阀膜连接。
  6. 根据权利要求1-5任一项所述的液体转移装置，其特征在于，
    所述弹性阀膜以一体或分体的形式铺设在所述液路阀板上。
  7. 根据权利要求1所述的液体转移装置，其特征在于，
    所述液路阀板上还设置有出液口、出液通道；
    所述出液通道一端与所述出液口导通，另一端与一个所述阀孔导通，并由所述膜阀控制实现与所述移液通道的导通或者阻断。
  8. 根据权利要求7所述的液体转移装置，其特征在于，所述液路阀板的顶部具有第一覆膜区域；所述第一覆膜区域设置有所述出液通道。
  9. 根据权利要求7所述的液体转移装置，其特征在于，所述液路阀板还设置至少一个接液管；所述接液管与所述出液口导通。
  10. 根据权利要求1所述的液体转移装置，其特征在于，
    所述液路阀板还设置气路接头；所述气路接头与一个所述阀孔导通，并由所述膜阀控制实现与所述移液通道的导通或者阻断。
  11. 根据权利要求1所述的液体转移装置，其特征在于，
    所述液路阀板还设置定量池，设置在两个相邻的所述试剂管之间，且位于所述移液通道内。
  12. 根据权利要求1所述的液体转移装置，其特征在于，
    部分所述试剂管内置活塞推杆。
  13. 根据权利要求1所述的液体转移装置，其特征在于，
    所述试剂管为密封腔室，包括依次设置的废液室、样本室、裂解室、空室、洗液室、洗脱液室、磁吸洗脱室、混合管、矿物油室、过量室、二次加样室。
  14. 根据权利要求13所述的液体转移装置，其特征在于，
    所述密封腔室通过密封件进行密封，所述密封件选自覆膜或活塞。
  15. 根据权利要求13所述的液体转移装置，其特征在于，所述移液通道为四条，第一移液通道用于所述废液室、样本室、裂解室、空室、洗液室、洗脱液室的液体转移，第二移液通道用于所述磁吸洗脱室、混合管的液体转移，第三移液通道用于所述矿物油室、过量室的液体转移，第四移液通道用于所述二次加样室的液体转移。
  16. 根据权利要求15所述的液体转移装置，其特征在于，
    所述液路阀板还设置定量池，位于所述矿物油室、过量室之间的所述移液通道内。
  17. 根据权利要求15所述的液体转移装置，其特征在于，
    所述弹性阀膜还具有三个第二预设区域；所述第二预设区域与所述液路阀板之间形成三个所述膜阀，分别用于导通或者阻断相邻的所述第一移液通道与第二移液通道，相邻的所述第二移液通道与第三移液通道，以及相邻的所述第三移液通道与第四移液通道。
  18. 一种多路并联的液体转移装置，其特征在于，每一路包括如权利要求1-17任一项所述的液体转移装置。
PCT/CN2022/089375 2022-04-26 2022-04-26 液体转移装置及多路并联的液体转移装置 WO2023206096A1 (zh)

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