WO2021000749A1 - 分子检测*** - Google Patents

分子检测*** Download PDF

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Publication number
WO2021000749A1
WO2021000749A1 PCT/CN2020/097140 CN2020097140W WO2021000749A1 WO 2021000749 A1 WO2021000749 A1 WO 2021000749A1 CN 2020097140 W CN2020097140 W CN 2020097140W WO 2021000749 A1 WO2021000749 A1 WO 2021000749A1
Authority
WO
WIPO (PCT)
Prior art keywords
detection system
molecular detection
screw
microfluidic
motor
Prior art date
Application number
PCT/CN2020/097140
Other languages
English (en)
French (fr)
Inventor
胡军荣
徐强
崔相民
Original Assignee
申翌生物科技(杭州)有限公司
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from CN201921681136.8U external-priority patent/CN210725000U/zh
Priority claimed from CN201921681140.4U external-priority patent/CN210839207U/zh
Priority claimed from CN201921681583.3U external-priority patent/CN211329427U/zh
Priority claimed from CN201910953746.7A external-priority patent/CN112175817A/zh
Priority claimed from CN201921681163.5U external-priority patent/CN211205988U/zh
Application filed by 申翌生物科技(杭州)有限公司 filed Critical 申翌生物科技(杭州)有限公司
Priority to EP20834585.0A priority Critical patent/EP3995565A4/en
Publication of WO2021000749A1 publication Critical patent/WO2021000749A1/zh
Priority to US17/542,512 priority patent/US20220097059A1/en

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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
    • 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
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502715—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
    • 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
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/50273—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means or forces applied to move the fluids
    • 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
    • C12M1/34—Measuring or testing with condition measuring or sensing means, e.g. colony counters
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/16—Reagents, handling or storing thereof
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0663—Whole sensors
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0672—Integrated piercing tool
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0819—Microarrays; Biochips
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0887—Laminated structure
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/12—Specific details about materials
    • B01L2300/123—Flexible; Elastomeric
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/18—Means for temperature control
    • B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
    • B01L2300/1827—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks using resistive heater
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0478—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure pistons
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0481—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure squeezing of channels or chambers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0677—Valves, specific forms thereof phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers
    • B01L2400/0683—Valves, specific forms thereof phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers mechanically breaking a wall or membrane within a channel or chamber
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6844—Nucleic acid amplification reactions
    • C12Q1/686—Polymerase chain reaction [PCR]

Definitions

  • the present invention relates to the field of molecular biology. Specifically, the present invention relates to a molecular detection system.
  • Biomolecules and other analytes can be detected by selective or specific probes that can react with them.
  • detection of protein, DNA, RNA and other biomolecules has become an effective means of disease diagnosis and prediction.
  • the advantages of molecular diagnostic technology such as low sample consumption, accurate diagnostic results, high sensitivity, and high throughput, make the technology develop rapidly in modern medicine.
  • the most widely used detection method is fluorescent label detection technology.
  • This technology uses fluorescent molecular groups as labels, and connects the fluorescent labels to probe molecules or target molecules through chemical modification.
  • the detection instrument irradiates a specific wavelength of laser light on the sample to be detected, and can achieve quantitative detection of specific molecules by detecting the corresponding fluorescence signal intensity.
  • the existing molecular detection methods still need to be improved.
  • the present invention is based on the inventor's discovery of the following facts and problems:
  • auxiliary work For example, according to the specific conditions of the sample, the nucleic acid in the sample needs to be purified, the required molecular fragments are extracted, and the corresponding detection reagents are prepared, and finally the sample and the detection reagent are mixed and placed in the detection instrument for detection.
  • the auxiliary work is cumbersome and requires different instruments or tools to complete, so that molecular testing must be performed by professionals in a standardized laboratory environment, with limited application scenarios, long testing time, and low efficiency.
  • the present invention proposes a molecular detection system.
  • the molecular detection system can perform fully automated rapid detection of samples to be tested.
  • the present invention provides a molecular detection system.
  • the molecular detection system includes: a substrate on which a fixing device, a driving device, a detection device, and a temperature control device are arranged; wherein the fixing device is suitable for fixing a container containing a sample to be tested;
  • the driving device is adapted to drive the container to preprocess the sample to be tested;
  • the detection device is adapted to test the sample to be tested after the pretreatment;
  • the temperature control device is adapted to control the State the temperature of the sample to be tested.
  • the container containing the sample to be tested is fixed on the fixing device.
  • the sample to be tested flows in the container while completing the nucleic acid extraction and PCR reaction in the sample, thereby Obtain samples suitable for detection by the detection device.
  • the temperature control device can heat a part of the fixing device, so as to realize the extraction of nucleic acid in the sample and the PCR reaction.
  • the detection device can perform real-time fluorescence measurement of the amplified product, and obtain the detection result according to the data of the fluorescence signal change.
  • the molecular detection system of the present invention integrates the purification and extraction of sample nucleic acid into one device, and realizes the fully automated completion of molecular detection, which solves the limitation of traditional molecular detection methods due to experimental conditions and staff.
  • the resulting application scenarios are limited and inefficient.
  • the molecular detection system according to the foregoing embodiment of the present invention may also have the following additional technical features:
  • the base includes a first base, a support, and a shaft sleeve that are connected.
  • the fixing device includes a slot, a first motor, a first nut, a first clamping member, a second clamping member, and a connecting rod; the first motor passes through the first The nut is connected to the first clamping member, the first clamping member and the second clamping member are connected by the connecting rod, and the slot is provided between the first clamping member and the first clamping member. Between two clamping members.
  • the molecular detection system further includes: a first compression spring, and the first compression spring is provided between the clamping slot and the second clamping member.
  • the molecular detection system further includes: a first heat dissipation component; the first heat dissipation component is provided under the card slot.
  • the driving device includes a second motor, a third motor, a thimble, and a push rod; the second motor is connected to the thimble, and the third motor is connected to the push rod.
  • the molecular detection system further includes: a linear guide rail and a slider, and the push rod is arranged on the linear guide rail through the slider.
  • the detection device includes a light path detection unit
  • the temperature control device includes a chip temperature cycle control
  • one end of the detection device is connected to the card slot through the chip temperature cycle control.
  • the molecular detection system further includes: a control system, the control system is respectively connected with the fixing device, the driving device, the detection device and the temperature control device, and suitable For controlling the fixing device, the driving device, the detection device and the temperature control device to work together to perform the detection on the sample to be tested
  • the molecular detection system further includes: a sliding device, which is connected to the driving device and the fixing device, and is adapted to keep the position of the container relatively fixed.
  • the sliding device includes: a second base; a first guide rod, the first guide rod is movably inserted in a fixed limit located at one end of the second base In the through hole; the second guide rod, the second guide rod is movably inserted in the movable limit through hole on the other end of the second base; the first connecting bracket, the first connecting bracket A third through hole is provided on the upper end of the first guide rod and the upper end of the second guide rod is respectively connected to both ends of the first connecting bracket; the second connecting bracket, the upper end of the first guide rod The lower end and the lower end of the second guide rod are respectively connected to both ends of the second connecting bracket; a first screw motor, the first screw motor is arranged on the second base, and the first The screw in the screw motor is perpendicular to the second base and passes through the third through hole.
  • the screw drives the first connecting bracket to move and move the first guide rod, the second The guide rod and the second connecting bracket.
  • the diameter of the first guide rod is 0.1 to 0.3 mm smaller than the inner diameter of the fixed limit through hole, and the diameter of the second guide rod is smaller than that of the movable limit through hole.
  • the inner diameter is 0.5-2mm smaller.
  • the upper end of the first guide rod and the upper end of the second guide rod are respectively connected to the two ends of the first connecting bracket with bolts, and the lower end of the first guide rod and the The lower ends of the second guide rods are respectively connected with two end bolts of the second connecting bracket.
  • the screw rod is connected to the third through hole through a thread.
  • the sliding device further includes: a first screw nut fixedly connected to the third through hole and matingly connected with the screw rod.
  • the first connecting bracket moves in an interval of 5 to 55 mm from the second base.
  • a lubricating layer is formed on the surfaces of the fixed limit through hole and the movable limit through hole.
  • the lubricating layer is a lubricating oil layer or a graphite layer, and the thickness of the lubricating layer is 0.01-1 mm.
  • the screw in the first screw motor, is a trapezoidal screw, a ball screw or a planetary ball screw, and the motor is a DC motor, a stepping motor or a servo motor.
  • the molecular detection system further includes: an optical path imaging automatic adjustment device, the optical path imaging automatic adjustment device is connected to the detection device, and includes a photoelectric sensor and a convex lens, the optical path imaging automatic adjustment device The device is adapted to automatically adjust the distance between the photoelectric sensor and the convex lens.
  • the optical path imaging automatic adjustment device includes: a third base; a photoelectric sensor, the photoelectric sensor is fixed on the third base; an adjustment bracket, the adjustment bracket is movably The distance between the photoelectric sensor and the convex lens is adjusted by moving the adjustment bracket; the second screw motor, the second A screw motor is fixed on the third base, and the screw in the second screw motor passes through the adjustment bracket and drives the adjustment bracket to move.
  • the adjusting bracket is threadedly connected with the screw rod.
  • the optical path imaging automatic adjustment device further includes: a second screw nut, the second screw nut is fixedly connected to the adjustment bracket and matched with the screw rod.
  • the moving distance of the adjusting bracket is not more than 30 mm.
  • the distance between the photosensor and the convex lens is 30-60 mm.
  • the peripheral wall of the adjusting bracket is provided with a plurality of protrusions that abut against the inner wall of the third base.
  • the second screw motor and the photoelectric sensor are intelligently linked through the CPU end.
  • the screw in the second screw motor, is a trapezoidal screw, a ball screw or a planetary ball screw, and the motor is a DC motor, a stepping motor or a servo motor.
  • the card slot in the molecular detection system includes: a housing, the upper part of the housing is open and an accommodating space is defined inside; a positioning hole, the positioning hole is provided in the housing A positioning column, one end of the positioning column extends into the positioning hole; a heating assembly, the heating assembly is provided in the containing space; a second compression spring, the second compression spring is provided in the The bottom of the containing space is connected with the heating component.
  • the card slot further includes a fixing screw, the fixing screw extends through the through hole into the receiving space and is connected to the heating assembly, and the second compression spring is sleeved On the fixing screw.
  • each of the positioning holes and the positioning pillars includes a plurality of positioning holes, and each positioning hole is arranged in a one-to-one correspondence with each positioning pillar.
  • one end of the positioning column protruding into the positioning hole is conical.
  • the heating assembly includes a connected heating plate and a heat conducting block, and the heat conducting block is connected with the second compression spring and the fixing screw.
  • a heating chamber is formed on the heat conducting block.
  • the lower part of the heat conducting block is provided with a limiting hole, and the fixing screw extends into the limiting hole.
  • the diameter of the via hole is larger than the diameter of the fixing screw.
  • the present invention provides a microfluidic kit suitable for the molecular detection system of the above embodiment.
  • the microfluidic kit includes: a box body provided with a reagent area, a sample area, and a reaction area; a microfluidic kit chip, the microfluidic kit chip includes a microfluidic A fluid control pipe, the microfluidic pipe is provided with a piercing member facing the liquid outlet, and the microfluidic kit chip is respectively connected with the reagent area, the sample area and the reaction area through the microfluidic pipe Area connected.
  • the microfluidic kit of the above embodiment of the present invention can not only introduce the sample to be tested in the sample area and the reagents in the reagent area (if the reaction area has lyophilized powder reagents, the reagent area can also store diluent) through the microfluidic pipeline
  • the reaction zone reacts, so as to realize the detection of the sample, and there is no need to set additional external parts such as elastic valves to realize the disconnection and connection of the pipeline.
  • the microfluidic tube used for the microfluidic kit chip includes: a tube, a sealing film and a piercing member, the end of the tube is formed of an elastic material, and the liquid outlet is provided at On the side wall of the end; the sealing film is arranged at the liquid outlet and seals the liquid outlet; the piercing member having a tip is arranged on the inner wall of the end opposite to the liquid outlet On the other hand, the tip portion faces the liquid outlet and pierces the sealing film when the end portion is squeezed by an external force. Therefore, the microfluidic pipe can realize the dual functions of sealing the microfluidic pipe before use and unsealing during use, and the sealing of the pipe can be realized without adding external pressure parts when storing raw materials.
  • the piercing member and the liquid outlet are provided on the same pipe diameter of the pipeline. This makes it easier to pierce the sealing film when force is applied to the end of the pipe.
  • the sealing film is tin foil, plastic film or kraft paper. This can effectively prevent the raw materials stored in the microfluidic pipeline from seeping out through osmosis.
  • the thickness interval of the sealing film is 0.01 to 0.2 mm. Therefore, it is not only beneficial to seal the liquid outlet, but also can reduce the difficulty of piercing the sealing film by the piercing member.
  • the tip of the tip portion has a tapered structure, and the tapered structure is a cone or a polygonal pyramid. This can further facilitate the piercing of the sealing film.
  • the tip portion is formed by a triangular surface, and one side of the triangular surface is provided on the inner wall of the end opposite to the liquid outlet, and the vertex corresponding to the side is formed The tip of the tip. This can further facilitate the piercing of the sealing film.
  • one side of the triangular surface provided on the inner wall of the end portion is linear, V-shaped, arc-shaped or U-shaped.
  • the piercing member is integrally formed with the pipe.
  • the structure of the microfluidic tube can be further simplified, and it is further advantageous to pierce the sealing film.
  • the pipe includes a first plate and an elastic plate, the lower surface of the first plate has a groove, and the groove is provided with a liquid outlet; the elastic plate is arranged on the The lower surface of the first plate seals the groove, so that the groove forms a microfluidic channel; wherein, the piercing member is arranged in the microfluidic channel and at a position opposite to the liquid outlet, and the The piercing member is connected with the lower surface of the first plate through an elastic member, and the piercing member pierces the sealing film when the elastic plate is pressed by an external force.
  • Fig. 1 is a schematic structural diagram of a molecular detection system according to an embodiment of the present invention.
  • Fig. 2 is a schematic structural diagram of a molecular detection system according to an embodiment of the present invention.
  • Fig. 3 is a schematic structural diagram from another perspective of the molecular detection system according to an embodiment of the present invention.
  • Fig. 4 is a schematic structural diagram from another perspective of the molecular detection system according to an embodiment of the present invention.
  • Fig. 5 is a schematic structural diagram from another perspective of the molecular detection system according to an embodiment of the present invention.
  • FIG. 6 is a schematic diagram of the structure of some components in the fixing device, the driving device and the temperature control device in the molecular detection system of the embodiment of the present invention.
  • FIG. 7 is a schematic diagram of the structure of some components in the detection device in the molecular detection system of the embodiment of the present invention.
  • FIG. 8 is a schematic structural diagram of some components in the detection device in the molecular detection system of the embodiment of the present invention from another perspective.
  • FIG. 9 is a schematic diagram of the structure of some components in the fixing device and the driving device in the molecular detection system of the embodiment of the present invention.
  • FIG. 10 is a schematic structural view of some components in the fixing device and the driving device in the molecular detection system of the embodiment of the present invention from another perspective.
  • FIG. 11 is a schematic structural view from another perspective of some components in the fixing device and the driving device in the molecular detection system of the embodiment of the present invention.
  • Fig. 12 is a schematic structural diagram of a microfluidic kit according to an embodiment of the present invention.
  • Fig. 13 is a schematic structural diagram of a sliding device in a molecular detection system according to an embodiment of the present invention.
  • Fig. 14 is a schematic structural diagram of a sliding device in a molecular detection system according to another embodiment of the present invention.
  • 15 is a cross-sectional view of the second base in the molecular detection system according to an embodiment of the present invention along the longitudinal direction
  • Fig. 16 is a schematic structural diagram of a sliding device in a molecular detection system according to another embodiment of the present invention.
  • Fig. 17 is a schematic structural diagram of a sliding device in a molecular detection system according to another embodiment of the present invention.
  • Fig. 18 is a schematic structural diagram of a sliding device in a molecular detection system according to another embodiment of the present invention.
  • Fig. 19 is a schematic structural diagram of a light path imaging automatic adjustment device in a molecular detection system according to an embodiment of the present invention.
  • Fig. 20 is a schematic structural diagram of the limit relationship between the adjustment bracket and the third base of the optical path imaging automatic adjustment device in the molecular detection system according to an embodiment of the present invention.
  • 21 is a schematic diagram of the structure of a card slot in a molecular detection system according to an embodiment of the present invention.
  • FIG. 22 is a schematic structural diagram of another view of the card slot in the molecular detection system according to an embodiment of the present invention.
  • FIG. 23 is a schematic structural diagram of a kit suitable for the card slot in the molecular detection system of the embodiment of the present invention.
  • Figure 24 is a structural schematic diagram of the coordinated installation of the card slot and the reagent kit in the molecular detection system according to an embodiment of the present invention.
  • Fig. 25 is a schematic structural diagram from another perspective of the coordinated installation of the card slot and the kit in the molecular detection system according to an embodiment of the present invention.
  • Figure 26 is a schematic structural diagram of a microfluidic kit according to an embodiment of the present invention.
  • Fig. 27 is a schematic structural diagram of a microfluidic pipe according to an embodiment of the present invention.
  • Fig. 28 is a cross-sectional view of a microfluidic pipe in a direction perpendicular to the pipe according to an embodiment of the present invention.
  • Figure 29 is a cross-sectional view of a microfluidic pipe in a direction parallel to the pipe according to an embodiment of the present invention.
  • Figure 30 is a top view of a piercing member according to an embodiment of the present invention.
  • Fig. 31 is a schematic structural diagram of a microfluidic pipe according to another embodiment of the present invention.
  • Fig. 32 is a schematic structural diagram of a tip portion of a microfluidic tube according to another embodiment of the present invention.
  • Fig. 33 is a cross-sectional view of a microfluidic pipe in a direction perpendicular to the pipe according to another embodiment of the present invention.
  • Fig. 34 is a cross-sectional view of a microfluidic pipe in a direction parallel to the pipe according to another embodiment of the present invention.
  • Fig. 35 is a top view of a piercing member according to another embodiment of the present invention.
  • Fig. 36 is a perspective view showing the partial composition of a microfluidic pipe according to an embodiment of the present invention.
  • Figure 37 is a perspective view of a microfluidic tube according to an embodiment of the present invention.
  • Fig. 38 is a perspective view showing the partial composition of a microfluidic pipe according to another embodiment of the present invention.
  • Fig. 39 is a perspective view of a microfluidic tube according to still another embodiment of the present invention.
  • first and second are only used for descriptive purposes, and cannot be understood as indicating or implying relative importance or implicitly indicating the number of indicated technical features. Therefore, the features defined with “first” and “second” may explicitly or implicitly include at least one of the features. In the description of the present invention, "a plurality of” means at least two, such as two, three, etc., unless otherwise specifically defined.
  • the first feature “on” or “under” the second feature may be in direct contact with the first and second features, or the first and second features may be indirectly through an intermediary. contact.
  • the "above”, “above” and “above” of 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 level of the first feature is higher than the second feature.
  • the “below”, “below” and “below” of the second feature of the first feature may mean that the first feature is directly below or obliquely below the second feature, or simply means that the level of the first feature is smaller than the second feature.
  • the auxiliary work is cumbersome and requires different instruments or tools to complete, so that molecular testing must be performed by professionals in a standardized laboratory environment, with limited application scenarios, long testing time, and low efficiency.
  • the present invention proposes a molecular detection system.
  • the molecular detection system includes: a substrate 100 and a fixing device 200, a driving device 300, a detection device 400 and a temperature control device 500 arranged on the substrate 100.
  • the fixing device 200 is suitable for fixing the container containing the sample to be tested;
  • the driving device 300 is suitable for driving the container to preprocess the sample to be tested;
  • the testing device 400 is suitable for testing the preprocessed sample to be tested, and the temperature control device 500 is suitable To regulate the temperature of the sample to be tested.
  • FIGS. 1-12 are schematic diagrams of the molecular detection system under different viewing angles.
  • FIG. 6 shows in detail the relative positional relationship of some components in the fixing device 200, the driving device 300 and the temperature control device 500.
  • 7 and 8 respectively show the relative position relationship of some components in the detection device 400 from different perspectives.
  • 9 to 11 respectively show the relative positional relationship of some components in the fixing device 200 and the driving device 300 from different perspectives.
  • Figure 12 is a schematic diagram of the structure of a container containing a sample to be tested.
  • the base 100 includes a first base 1, a support 2 and a shaft sleeve 3 that are connected.
  • the first base 1, the support 2 and the shaft sleeve 3 together form the support structure of the molecular detection system, and provide support for the fixing device 200, the driving device 300, the detection device 400 and the temperature control device 500.
  • the fixing device 200 is suitable for fixing the container containing the sample to be tested, and can ensure that the position of the container containing the sample to be tested is relatively fixed during the detection process, thereby ensuring that the pretreatment and the detection process of the sample to be tested are performed stably. According to an embodiment of the present invention, referring to Figs.
  • the fixing device includes a slot 6, a first motor 4, a first nut 5 and a clamping device 8, wherein the clamping device 8 includes a first clamping member 81, a Two clamping members 82 and a connecting rod 83; the first motor 4 is connected to the first clamping member 81 by a first nut 5, the first clamping member 81 and the second clamping member 82 are connected by a connecting rod 83, and the slot 6 It is provided between the first clamping member 81 and the second clamping member 82.
  • the card slot 6 is provided on the first base 1, the first motor 4 is provided on the sleeve 3, and the connecting rod 83 in the clamping device 8 passes through the bracket 2 to connect to the first clamping member 81 and the second clamping member 82.
  • the container containing the sample to be tested is placed in the slot 6, as the first motor 4 drives the first nut 5 to move, the first clamping member 81 and the second clamping member 82 in the clamping device 8
  • the container in the card slot 6 can be clamped to ensure that the position of the container is relatively fixed during the detection process.
  • the molecular detection system may further include: a first compression spring 10.
  • the first compression spring 10 is arranged between the slot 6 and the second clamping member 82 and is loosely connected by the screw 9. Therefore, during the movement of the clamping device 8, the container in the clamping slot 6 is clamped by the action of the first compression spring 10.
  • the molecular detection system may further include: a first heat dissipation component 61.
  • the first heat dissipation component 61 is arranged under the card slot 6.
  • the first heat dissipation component 61 may be installed on the first base 1 and arranged under the card slot 6.
  • the specific type of the first heat dissipation component 61 is not particularly limited. For example, a fin type heat sink, a plate type heat sink, etc. may be used.
  • the driving device 300 is adapted to drive the container containing the sample to be tested and the sample to be tested for pretreatment. Pretreatment includes extraction of nucleic acid from the sample to be tested and PCR reaction.
  • Pretreatment includes extraction of nucleic acid from the sample to be tested and PCR reaction.
  • the kit includes a sample chamber 6-1, a dilution chamber 6-2, an injection chamber 6-3, a piston 6-4, a PCR chamber 6-5, a buffer chamber 6-6, a sample sealing film 6-7, and dilution Sealing film 6-8, microfluidic pipeline 6-9, sample control valve 6-10, dilution control valve 6-11, first PCR control valve 6-12, second PCR control valve 6-13, each unit passes The microfluidic lines 6-9 are connected to form a connected loop.
  • the sample chamber 6-1 contains the lysis material in the form of freeze-dried powder
  • the PCR chamber 6-5 contains the reverse transcriptase and the PCR material in the form of freeze-dried powder
  • the dilution chamber 6-2 contains the appropriate diluent .
  • the parts where the sample chamber 6-1 and the dilution chamber 6-2 communicate with the microfluidic pipeline 6-9 are sealed with a sample sealing film 6-7 and a dilution sealing film 6-8, respectively, so that the pyrolysis material in the sample chamber 6-1 It is isolated from the diluent in the dilution chamber 6-2 and the reverse transcriptase and PCR raw materials in the PCR chamber 6-5.
  • the piston 6-4 is at the top of the injection chamber 6-3 (the injection chamber is in a state where the piston is filled).
  • the microfluidic kit starts to work.
  • the liquid flows to the injection chamber 6-3 through the dilution control valve 6-11.
  • the mixture in the PCR chamber 6-5 will expand due to the high temperature, and the liquid in the expansion process will overflow It can flow into the buffer chamber 6-6 through the second PCR control valve 6-13.
  • the thermostatic stage After the thermostatic stage is over, close the first PCR control valve 6-12 and the second PCR control valve 6-13, and start the PCR chamber 6-5. Perform temperature cycle control, and finally complete the amplification of nucleic acids in the sample.
  • the driving device 300 includes a second motor 11, a third motor 13, a thimble 12, and a push rod 16.
  • the second motor 11 is a linear motor
  • the third motor 13 is a first wire.
  • a rod motor, the second motor 11 is directly connected to the thimble 12, and the third motor 13 is connected to the push rod 16 through a second nut 15.
  • the second motor 11 and the thimble 12 can be directly mounted on the first base 1, and the third motor 13 can be mounted on the first base 1 through the motor bracket 14.
  • the sample sealing film 6-7 and the dilution sealing film 6-8 in the above kit are respectively opposite to a thimble 12, and then the thimble is driven by the second motor 11 12 Performing linear motion can realize the puncture of the sample sealing film 6-7 and the dilution sealing film 6-8, so that the microfluidic pipeline in the kit can be connected.
  • the third motor 13 can drive the push rod 16 to move linearly through the second nut 15 to control the reciprocating motion of the piston 6-4 in the kit, so that the sample in the kit flows in the microfluidic tube in the kit .
  • a protruding piercing member (not shown in the drawings) is provided inside the microfluidic tube of the kit, and the piercing member has a tip.
  • the piercing member is arranged at a position opposite to the sample sealing film 6-7 and the dilution sealing film 6-8, and the tip of the piercing member faces the sample sealing film 6-7 and the dilution sealing film 6-8. Therefore, the thimble 12 can pierce the sample sealing film 6-7 and the dilution sealing film 6-8 by pressing the piercing member without directly contacting the sample, and the microfluidic tube is always connected to the outside ( The equipment) is in an isolated state, thereby effectively avoiding the contamination of the equipment by the sample.
  • the PCR reactions in the kit are all carried out in a sealed PCR reaction chamber, and the product will not volatilize into the equipment cavity through aerosol during the traditional PCR experiment.
  • the molecular detection system may further include a linear guide rail 17 and a slider 18, and the push rod 16 is provided on the linear guide rail 17 through the slider 18.
  • the push rod 16 and the sliding block 18 can be fixed by a second nut 15.
  • the push rod 16 makes a linear motion on the linear guide 17, thereby controlling the expansion and contraction of the piston 6-4.
  • the detection device 400 is adapted to detect the pre-processed sample to be tested, and the temperature control device 500 is adapted to regulate the temperature of the sample to be tested.
  • the detection device includes an optical path detection unit 19 and the temperature control device 500 includes a chip temperature cycle control 7. While the temperature control device 500 performs temperature cycle control on the samples in the PCR chamber 6-5, the detection device 400 can perform real-time measurement of the amplified products in the PCR chamber 6-5 to obtain the fluorescent signal of the amplified products. Probes are pre-arranged in the chamber, and the amplified products can hybridize with the probes to release fluorescent groups.
  • the fluorescent groups With the increase of the amplified products, the fluorescent groups also increase continuously, which leads to the continuous enhancement of the fluorescent signal, and finally When the sensitivity range of the detection device 400 is reached, the detected data changes significantly.
  • the analysis software defines the number of cycles of amplification corresponding to the significant changes in this data as the CT value, and the CT value appears in a certain area
  • the test results are respectively defined as positive, and the rest are defined as negative, so that the data of changes in the fluorescence signal is converted into a negative-positive test result.
  • the detection result can be obtained by PCR reaction on bacterial 16S rRNA.
  • the primers used in the PCR reaction include forward primer 63f (5'-CAG GCC TAA CAC ATG CAA GTC-3') and reverse primer 1387r (5'-GGG CGG TGT GTA CAA GGC-3').
  • the detection result can be obtained by PCR reaction on influenza virus FluA.
  • the primers used in the PCR reaction include forward primer (5'-CAGAGACTTGAAGATGTTTTTGC-3') and reverse primer (5'-CTACGCTGCAGTCCTCGCTC-3'), and probe (5'-CAAGACCAATCCTGTCACCTCTGA-3').
  • one end of the detection device is connected to the card slot through a temperature control device.
  • a temperature control device As shown in Figures 7 and 8, by fixing the kit in the card slot 6, the PCR chamber 6-5 in the kit is adjacent to the temperature circulation control 7 in the temperature control device, so that the temperature control device can check the PCR chamber 6-5 Temperature control.
  • the molecular detection system further includes a control system 20.
  • the control system is respectively connected with the fixing device, the driving device, the detection device and the temperature control device, and is suitable for controlling the fixing device, the driving device, the detection device and the temperature control device to work together to detect the sample to be tested.
  • the molecular detection system of the present invention further includes a sliding device, which is connected to the driving device and the fixing device, and is adapted to keep the container position relatively fixed.
  • the sliding device includes a second base 13-10, a first guide rod 13-20, a second guide rod 13-30, a first connecting bracket 13-40, a second connecting bracket 13-50 and a first wire Rod motor 13-60.
  • One end of the second base 13-10 is provided with a fixed limit through hole 13-11, and the other end is provided with a movable limit through hole 13-12;
  • the first guide rod 13-20 is movably inserted in the fixed limit In the through hole 13-11;
  • the second guide rod 13-30 is movably inserted in the movable limit through hole 13-12;
  • the first connecting bracket 13-40 has a third through hole 13-41, the first connection Both ends of the bracket 13-40 are respectively connected to the upper ends of the first guide rod 13-20 and the second guide rod 13-30; the two ends of the second connecting bracket 13-50 are respectively connected to the first guide rod 13-20 and the second guide rod 13-20.
  • the lower end of the guide rod 13-30 is connected; the first screw motor 13-60 is arranged on the second base 13-10 and the screw 13-61 on the first screw motor 13-60 is connected to the second base 13 -10 is vertical, and the screw rod 13-61 passes through the third through hole 13-41 and drives the first connecting bracket 13-40 to move and move the first guide rod 13-20, the second guide rod 13-30 and the second connection Bracket 13-50.
  • the screw 13-61 of the first screw motor 13-60 rotates, it will drive the first connecting bracket 13-40 to move with the screw 13-61, while the first bracket 13-40 drives the first guide rod 13-20 ,
  • the second guide rod 13-30 and the second connecting bracket 13-50 move.
  • the first guide rod 13-20 slides along the fixed limit through hole 13-11 during the movement process, and the fixed limit through hole 13- 11 Make the first guide rod 13-20 slide along the longitudinal direction of the second base 13-10 and keep the sliding direction basically unchanged, while the second guide rod 13-30 slides in the movable limit through hole 13-12, the movable limit
  • the position through holes 13-12 can provide a certain movement space for the second guide rod 13-30 in the transverse direction of the second base 13-10, so that the second guide rod 13-30 can move with the first bracket 13-40.
  • the sliding device is not only simple in structure and easy to install on the guide rods, but also allows the double guide rods to slide smoothly in the through holes of the second base 13-10 when the double guide rods are not parallel.
  • the "horizontal" in the present invention is as shown in FIG. 13, the "longitudinal” is a direction perpendicular to the "horizontal”, and the "upper end” and the lower end are based on the direction from bottom to top in FIG. 13 In terms of direction.
  • the inner diameter of the fixed limit through hole 13-11 is greater than the diameter of the first guide rod 13-20 by 0.1 to 0.3 mm.
  • the inventor found that if the difference between the inner diameter of the fixed limit through hole 13-11 and the diameter of the first guide rod 13-20 is too large, when the first guide rod 13-20 slides along the longitudinal direction of the second base 13-10 It also slides along the lateral direction of the second base 13-10, which not only fails to effectively fix the sliding direction of the first guide rod 13-20, but also causes the first connecting bracket 13-40, the second connecting bracket 13-50 and the
  • the overall sliding direction of the second guide rod 13-20 is also constantly changing, which causes the guide rod to move on the second base 13-10, greatly reducing the smoothness of the guide rod sliding on the second base 13-10; If the difference between the inner diameter of the fixed limit through hole 13-11 and the diameter of the first guide rod 13-20 is too small, it will increase the difficulty of the first guide rod 13-20 sliding along the longitudinal direction of the second base 13-10.
  • the inner diameter of the fixed limit through hole 13-11 to be 0.1 ⁇ 0.3mm larger than the diameter of the first guide rod 13-20, not only can the first guide rod 13-20 slide smoothly in the second base 13-10 It can also ensure that the sliding direction of the first guide rod 13-20 during the sliding process is basically unchanged.
  • the inner diameter of the movable limit through hole 13-12 is 0.5-2 mm larger than the diameter of the second guide rod 13-30.
  • the inventor found that if the difference between the inner diameter of the movable limit through hole 13-12 and the diameter of the second guide rod 13-30 is too small, it is insufficient In order to eliminate the interference problem of the second base 13-10 on the movement of the guide rod, and if the difference between the inner diameter of the movable limit through hole 13-12 and the diameter of the second guide rod 13-30 is too large, the guide rod cannot be guaranteed Smooth operation.
  • the inner diameter of the movable limit through hole 13-12 by controlling the inner diameter of the movable limit through hole 13-12 to be larger than the diameter of the second guide rod by 0.5-2mm, it can not only eliminate the interference problem caused by the non-parallel double guide rods, but also make the double guide rods not parallel. It can also slide smoothly in the through holes of the second base 13-10, and at the same time, it can ensure the smooth movement of the guide rod.
  • the cross section of the movable limiting through hole 13-12 in the longitudinal direction of the second base 13-10 may be circular, oval or capsule shape, and the movable limiting through hole 13-12
  • the inner diameter of the second guide rod 13-30 is 0.5-2 mm larger than the diameter of the second guide rod 13-30, thereby providing sufficient space for the second guide rod 13-30 in the transverse direction of the second base 13-10.
  • the movable limit through hole 13-12 has an ellipse or capsule shape in the longitudinal direction of the second base 13-10, the long axis of the ellipse can be parallel to the movable limit through hole 13-12 to When the direction of the fixed limit through hole 13-11 is a capsule shape (as shown in Fig.
  • the length direction of the capsule shape can be parallel to the direction from the movable limit through hole 13-12 to the fixed limit through hole 13-11, And the width of the capsule shape can be the same as the inner diameter of the fixed limit through hole 13-11, which not only eliminates the interference problem caused by the non-parallel double guide rods, but also makes the double guide rods work in the non-parallel condition.
  • the second base 13-10 slides smoothly in the through hole, and at the same time, it can further ensure the smooth movement of the guide rod.
  • the second base 13-10 may further include a fixed shaft sleeve 13-13 and a movable shaft sleeve 13-14, and the fixed shaft sleeve 13-13 is fixed on the fixed shaft sleeve 13-13.
  • the first guide rod 13-20 slides through the fixed sleeve 13-13;
  • the movable sleeve 13-14 is fixed in the movable limit through hole 13-12, and the movable sleeve
  • the 13-14 bushing is provided with a sliding part 13-15 outside
  • the second base 13-10 is provided with a sliding track 13-16 matching the sliding part 13-15.
  • the sliding track 13-16 makes the movable bushing 13- 14 can move along the longitudinal and lateral directions of the second base 13-10. In this way, it is possible to further ensure the smooth movement of the guide rods on the basis of ensuring that the double guide rods can slide smoothly in the second base 13-10 under the condition that they are not parallel.
  • the two ends of the first connecting bracket 13-40 are respectively connected with the upper end bolts of the first guide rod 13-20 and the second guide rod 13-30, and the second connecting bracket 13-50 The two ends are respectively connected with the lower end bolts of the first guide rod 13-20 and the second guide rod 13-30.
  • the fixing method of the screw rod 13-61 and the third through hole 13-41 is not particularly limited, and those skilled in the art can make a selection according to actual needs.
  • the screw rod 13-61 and the third through hole 13-41 can be connected by threads. Therefore, there is no need to set a fixing nut.
  • the screw rod 13-61 and the third through hole 13-41 can be directly connected by threads to make the screw rod 13-61 is relatively fixed to the first connecting bracket 13-40, so that when the screw 13-61 rotates, the first connecting bracket 13-40 can be driven to move in the direction of the screw and the first guide 13-20 and the second guide The rod 13-30 and the second connecting bracket 13-50.
  • the above sliding device may further include: a first screw nut 13-70, the first screw nut 13-70 is matched and connected to the screw 13-61 and connected to the third Through holes 13-41 are fixedly connected. Therefore, the fixing strength of the screw rod 13-61 and the first connecting bracket 13-40 can be further improved, and the problem of abnormal movement due to the loose connection of the first connecting bracket 13-40 and the screw rod 13-61 can be effectively prevented.
  • the above-mentioned sliding device is applied to a molecular detection system to automatically control the pressing and fixing or loosening of the reagent kit.
  • the first connecting bracket 13-40 is away from the second base 13-10
  • the range of movement is 5 ⁇ 55mm. This can facilitate the fixation or replacement of the reagent kit and improve the detection efficiency.
  • the types of the motors and the screw rods 13-51 in the first screw motor 13-50 of the present invention are generally not limited, and those skilled in the art can select according to actual needs.
  • the motor may be a DC motor, a stepping motor or a servo motor
  • the screw rods 13-51 may be trapezoidal screw rods, ball screw rods or planetary ball screw rods. This can further improve the applicability of the present invention.
  • the surfaces of the fixed limit through holes 13-11 and the movable limit through holes 13-12 are both formed with a lubricating layer 13-80, which can further The friction and wear that may be generated between the first guide rod and the second guide rod and the second base during the sliding process are reduced, thereby further reducing the interference of the second base with the guide rod.
  • the material of the lubricating layer 13-80 in the present invention is not particularly limited, and those skilled in the art can choose according to actual needs.
  • the lubricating layer 80 may be formed of a liquid lubricant, a semi-solid lubricant or a solid lubricant, thereby effectively reducing the friction and wear that may occur between the double guide rod and the second base 13-10.
  • the lubricating layer 13-80 can be a lubricating oil layer or a graphite layer, thereby not only can ensure that the lubricating layer 80 also has good lubricating performance at room temperature, but also can prevent limiting through holes Rust, which can further avoid the interference of the guide rod by the second base during the movement.
  • the thickness of the lubricating layer 13-80 may be 0.01 to 1 mm, for example, 0.05 to 0.5 mm, 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, or 0.9 mm. This can further avoid the interference of the guide rod by the second base during the movement.
  • the present invention also proposes a sliding device.
  • the sliding device has all the features and advantages described above for the sliding device, and will not be described here. A repeat.
  • the molecular detection system of the present invention may further include: an optical path imaging automatic adjustment device, which is connected to the detection device and includes a photoelectric sensor and a convex lens, and the optical path imaging automatic adjustment device It is suitable for automatically adjusting the distance between the photoelectric sensor and the convex lens.
  • an optical path imaging automatic adjustment device when the screw of the second screw motor rotates, it will drive the adjustment bracket to move with the screw, and the convex lens is arranged on the adjustment bracket. Therefore, the movement of the adjustment bracket will also drive the convex lens to move.
  • the convex lens reciprocates in the direction of the screw, thereby changing the relative distance between the convex lens and the photoelectric sensor, and then changing the imaging position of the convex lens.
  • the optical path imaging automatic adjustment device can not only realize the detection of the object to be tested (ie, the test sample) at different object distances in the optical path system, but also obtain the best and clearest image.
  • the above-mentioned optical path imaging automatic adjustment device includes a third base 19-10, a photoelectric sensor 19-20, an adjustment bracket 19-30, a convex lens 19-40, and a second screw motor 19-50.
  • the photoelectric sensor 19-20 is fixed on the third base 19-10; the adjusting bracket 19-30 is movably arranged on the third base 19-10; the convex lens 19-40 is arranged on the adjusting bracket 19-30 and The distance between the convex lens 19-40 and the photoelectric sensor 19-20 can be adjusted by moving the adjusting bracket 19-30; the second screw motor 19-50 is fixed on the third base 19-10 and the second screw motor 19 The screw rod 19-51 on the -50 passes through the adjustment bracket 19-30 and drives the adjustment bracket 19-30 to move.
  • the optical path imaging automatic adjustment device when the screw 19-51 of the second screw motor 19-50 rotates, it will drive the adjustment bracket 19-30 to move with the screw 19-51, and the convex lens 19-40 is set on the adjustment bracket Therefore, the movement of the bracket 19-30 will drive the convex lens 19-40 to move, so that the convex lens 19-40 reciprocates along the screw 19-51 direction, thereby changing the convex lens 19-40 to the photoelectric sensor 19-20 Then, the imaging position of the convex lens 19-40 is changed, and finally the imaging of the convex lens 19-40 just falls on the receiving area of the photoelectric sensor 19-20, realizing the automatic adjustment of imaging. Therefore, the optical path imaging automatic adjustment device can not only realize the detection of the object to be tested (ie, the test sample) at different object distances in the optical path system, but also obtain the best and clearest image.
  • the object to be tested ie, the test sample
  • the fixing method of the screw rod 19-51 and the adjusting bracket 19-30 in the present invention is not particularly limited, and those skilled in the art can choose according to actual needs.
  • the screw rod 19-51 and the adjusting bracket 19-30 are connected by threads, so that the screw rod 19-51 and the adjusting bracket 19-30 can be relatively fixed, and the fixing strength of the two can be improved, so that the screw rod 19 When -51 rotates, it can drive the adjustment to move along the direction of screw rod 19-51, and then change the relative distance between convex lens 19-40 and photoelectric sensor 19-20.
  • the optical path imaging automatic adjustment device may further include: a second screw nut 19-60, and the second screw nut 19-60 is matched and connected to the screw 19-51 and is connected to the adjusting bracket 19- 30 fixed connection.
  • the fixing strength of the screw rod 19-51 and the adjusting bracket 19-30 can be further improved, and the problem of abnormal movement caused by the loose connection of the adjusting bracket 19-30 and the screw rod 19-51 can be effectively prevented.
  • the optical path imaging automatic adjustment device described in the present invention can be applied to a molecular automatic detection system to obtain the best and clearest image.
  • the maximum movable adjustment bracket 19-30 The distance is 30mm, for example, the moving distance of the adjusting bracket 19-30 can be 5mm, 10mm, 15mm, 20mm or 25mm. Therefore, the distance between the convex lens 19-40 and the photoelectric sensor 19-20 can be controlled by adjusting the bracket 19-30, so that the distance between the two can be changed in the range of 30-60mm, which can further help to obtain the best The clearest image.
  • a plurality of raised ribs 19-31 are formed on the peripheral wall of the adjusting bracket 19-30, and the raised ribs 19-31 abut against the third base 19-10 Inner wall.
  • the contact area between the adjustment bracket 19-30 and the third base 19-10 can be effectively reduced, thereby reducing the generation of the adjustment bracket 19-30 and the third base 19-10 during mutual movement.
  • the photoelectric sensor 19-20 can be intelligently linked to the second screw motor 19-50 through the CPU end.
  • the present invention can control the start or stop of the second screw motor according to the definition of the obtained image, so as to obtain the best and clearest image.
  • the CPU end controls the second screw motor 19-50 to turn on, and continuously adjusts the distance between the convex lens 19-40 and the photoelectric sensor 19-20 through the rotation of the screw 19-51 until the For the clearest image, when the obtained image definition reaches the requirement, the CPU end controls the second screw motor 19-50 to stop working.
  • the types of motors and screw rods 19-51 in the second screw motor 19-50 of the present invention are generally not limited, and those skilled in the art can make selections according to actual needs.
  • the motor may be a DC motor, a stepping motor or a servo motor
  • the screw rods 19-51 may be a trapezoidal screw rod, a ball screw rod or a planetary ball screw rod. This can further improve the applicability of the present invention.
  • the present invention also provides an optical path imaging automatic adjustment device.
  • the optical path imaging automatic adjustment device has all of the above described for the optical path imaging automatic adjustment device. The features and advantages will not be repeated here.
  • the card slot in the molecular detection system proposed by the present invention includes: a housing 2-100, a positioning hole 2-200, a positioning column 2-300, and a heating component 2-400 And the second compression spring 2-500.
  • the upper part of the housing 2-100 is open and an accommodating space 2-110 is defined inside;
  • the positioning hole 2-200 is provided on the side of the housing 2-100; one end of the positioning post 2-300 extends into the positioning hole 2-200
  • the heating assembly 2-400 is arranged in the accommodation space 2-110;
  • the second compression spring 2-500 is arranged at the bottom of the accommodation space 2-110 and is connected to the heating assembly 2-400.
  • the part to be heated of the reagent box can naturally fall on the heating assembly, and the opening for positioning (pre-processed positioning opening) on the reagent box is located slightly higher Position the positioning hole in the card slot of the kit.
  • the reagent box By moving the positioning column along the positioning hole toward the direction of the reagent box, the reagent box will also move slightly downward when the positioning column is locked into the positioning opening, and the second compression spring will be compressed and deformed. Under the cooperative action of the positioning column and the second compression spring, the part to be heated of the reagent box can be closely attached to the heating component in the card slot.
  • the card slot of the present invention is used to fix and heat the reagent kit, and the processing requirements for the reagent kit only need to meet the requirements for the heating part to be heated and the positioning port to cooperate with the positioning column, thereby greatly reducing the processing cost of the kit , And the part to be heated of the kit is tightly and stably attached to the heating component, which can meet the heating requirements of the kit in the experiment.
  • the bottom of the housing 2-100 is further provided with a through hole 2-120
  • the card slot further includes a fixing screw 2-600
  • the fixing screw 2-600 passes through the through hole 2- 120 extends into the containing space 2-110 and is connected to the heating assembly 2-400
  • the second compression spring 2-500 is sleeved on the fixing screw 2-600.
  • each of the positioning holes 2-200 and the positioning posts 2-300 may include multiple, and each positioning hole 2-200 and each positioning post 2-300 are arranged in one-to-one correspondence, that is, each Insert a positioning post 2-300 into the positioning hole 2-200.
  • the positioning posts 2-300 can be further used to press down the kit to be fixed, so that the parts to be heated closely adhere to the heating assembly 2-400 On the other hand, it can further improve the stability of the kit after fixation, and avoid displacement of the kit in the experiment.
  • two sets of positioning holes 2-200 and positioning posts 2-300 can be provided on both sides of one side wall of the housing 2-100, respectively.
  • the positioning post 2-300 it is further convenient to use the positioning post 2-300 to press down the kit to be fixed, so that the part to be heated is closely attached to the heating assembly 2-400, and further improves the stability of the kit after being fixed.
  • one end of the positioning column 2-300 extending into the positioning hole 2-200 is conical, in other words, along the direction in which the positioning column 2-300 extends into the positioning hole 2-200, the positioning The cross-sectional area of the column 2-300 gradually decreases as the positioning column, and the head of the positioning column 2-300 changes in a taper angle.
  • the heating assembly 2-400 includes a heating sheet 2-410 and a heat conducting block 2-420 that are connected, wherein the heat conducting block 2-420 is connected to the second compression spring 2-500.
  • the heating sheet 2-410 may be provided on one side of the heat conducting block 2-420.
  • the heating plate 2-410 can be controlled to generate heat, and the heating plate 2-410 can be used to indirectly heat the heat conducting block 2-420.
  • the temperature of the entire heat conducting block 2-420 is relatively uniform, which can further improve the heating effect on the part to be heated in the kit.
  • a heating chamber 2-421 may be formed on the heat conducting block 2-420. It should be noted that the specific shape of the heating chamber 2-421 is not particularly limited. The heating chamber 2-421 can be processed to match the shape of the part to be heated in the kit, so that the part to be heated in the kit can be The heating chamber 2-421 fits tightly.
  • the lower part of the heat conducting block 2-420 is provided with a limiting hole 2-422, and the fixing screw 2-600 can extend into the limiting hole 2-422.
  • the connection between the heat conducting block and the fixing screw 2-600 can be further facilitated.
  • the fixing screw 2-600 and the heat conducting block 2-420 are threadedly connected through the limiting hole 2-422.
  • the aperture of the via 2-120 is larger than the diameter of the fixing screw 2-600. Therefore, the fixing screw 2-600 can pass through the via 2-120 more easily and can move in any direction within a certain range of the housing 2-100, and the heating module 2-400 can follow the fixing screw within a certain range.
  • the 2-600 moves, and is subjected to the pressure generated by the deformation of the second compression spring 2-500, so as to closely fit the part to be heated of the reagent box.
  • kit 2-700 includes a part to be heated 2-710 and a positioning port 2-720.
  • the positioning opening 2-720 is processed on the kit and can be stably fixed with the card slot.
  • the kit 2-700 may include two positioning ports 2-720, wherein one positioning port 2-720 is a circular hole, and the other positioning port 2-720 is a waist-shaped hole.
  • the degree of freedom that the reagent kit 2-700 can move in the card slot can be further expanded, thereby further ensuring the stability of the reagent kit 2-700 being fixed by the positioning column 2-300 and the second compression spring 2-500, so that the reagent The to-be-heated part 2-710 of the box 2-700 is closely attached to the heating chamber 2-421 of the heat conducting block 2-420.
  • the part to be heated 2-710 enters the heating chamber 2-421, and the two positioning ports 2-720 are connected to the positioning hole 2-200 and the positioning column 2- respectively. 300 relative.
  • the positioning post 2-300 By controlling the positioning post 2-300 to move along the positioning hole 2-200 toward the kit 2-700, the positioning post 2-300 is locked into the positioning port 2-720.
  • the conical head of the positioning column 2-300 drives the reagent cartridge 2-700 to move downward through the positioning port 2-720, and causes the second compression spring 2 -500 is further compressed.
  • the fixing screw 2-600 can also drive the heat conducting block 2-420 to move freely within a certain range.
  • the molecular detection system proposed by the present invention uses the card slot of the above-mentioned embodiment to fix and heat the kit, which has low processing requirements for the kit, and the parts to be heated of the kit are tightly and stably attached to the heating components. It can meet the heating requirements of the kit in the experiment.
  • the present invention also proposes a card slot.
  • the card slot has all the features and advantages described above for the card slot, which will not be described here. A repeat.
  • the present invention provides a microfluidic kit suitable for the molecular detection system of the above embodiment.
  • the microfluidic kit includes: a box body 3-200 and a microfluidic kit chip 3-100, and a reagent area is provided in the box body 3-200 3-210, sample area 3-220, reaction area 3-230;
  • the microfluidic kit chip 3-100 includes a microfluidic pipe 3-110, and the microfluidic pipe 3-110 is provided with a liquid outlet 3-11
  • the piercing member 3-30 and the microfluidic kit chip 3-100 are respectively connected to the reagent area 3-210, the sample area 3-220, and the reaction area 3-230 through the microfluidic pipe 3-110.
  • the microfluidic kit can not only introduce the sample to be tested in the sample area and the reagents in the reagent area (if the reaction area has lyophilized powder reagents, the reagent area can also store diluent) into the reaction area for reaction through the microfluidic pipeline, In this way, the detection of the sample is realized, and there is no need to additionally set up external components such as elastic valves to realize the disconnection and connection of the pipeline.
  • the microfluidic tube 3-110 used for the microfluidic kit chip 3-100 includes a tube 3-10, a sealing film 3-20, and a piercing member 3-30.
  • the end of the pipe 3-10 is formed of an elastic material, and the side wall of the end has a liquid outlet 3-11; the sealing film 3-20 is arranged at the liquid outlet 3-11 to seal the liquid outlet 3-11
  • the piercing member 3-30 has a tip 3-31, the piercing member 3-30 is arranged on the inner wall of the end opposite to the liquid outlet 3-11 and the tip 3-31 faces the liquid outlet 3-11, when an external force When the end is squeezed, the tip 3-31 pierces the sealing film 3-20.
  • the microfluidic pipe is sealed by providing a sealing film 3-20 at the liquid outlet 3-11 of the pipe 3-10, and a tip is provided on the inner wall of the end of the pipe 3-10 opposite to the liquid outlet 3-11
  • the piercing member 3-30 of 3-31 and the tip 3-31 toward the liquid outlet 3-11 can make the microfluidic tube in a sealed state before use, and it can be applied to the end of the tube 3-10 in advance. Force, so that the piercing member 3-30 pierces the sealing film. Therefore, the sealing of the pipeline can be realized without adding external pressure parts when storing raw materials in the microfluidic pipeline, which simplifies the operation steps when the microfluidic pipeline is used.
  • end of the pipe 3-10 in the present invention refers to the end of the microfluidic pipe adjacent to the liquid outlet.
  • the piercing member is also called the piercing member
  • the liquid outlet is also called the liquid outlet.
  • the piercing member 3-30 and the liquid outlet 3-11 may be located on the same pipe diameter of the pipe 3-10.
  • the piercing member 3-30 can be directly opposed to the sealing film 3-20 at the liquid outlet portion, and when a force is applied to the end of the pipe 3-10, it is more favorable for the tip 3-31 of the piercing member to pierce the sealing film 3 -20.
  • the distance between the tip portion 3-31 of the piercing member and the sealing film 3-20 is not particularly limited, and those skilled in the art can follow the actual specifications and specifications of the microfluidic tube. It needs to be selected.
  • the distance between the tip 3-31 of the puncture member and the sealing film 3-20 can be 0.05-4 mm, or 0.05-2 mm, 0.05-1 mm, and so on.
  • the piercing member 3-30 will not pierce the sealing film 3-20 when the end of the pipe 3-10 is not subjected to external force, that is, ensure that the microfluidic pipe is in a sealed state during the storage of raw materials, but also When force is applied to the end of 3-10, it can also ensure that the sealing film 3-20 can be pierced, so that the raw materials stored in the microfluidic tube can seep out from the liquid outlet 3-11.
  • the sealing film 3-20 may be a film material that does not have a penetrating effect such as tin foil, plastic film or kraft paper. This can effectively prevent the raw materials stored in the microfluidic pipe from seeping out through osmosis when the pipe 3-10 is in a sealed state.
  • the thickness of the sealing film 3-20 may be 0.01 to 0.2 mm.
  • by controlling the thickness of the sealing film 3-20 to be 0.01-0.2 mm it is not only beneficial to seal the liquid outlet 3-11, but also can reduce the difficulty of piercing the sealing film 3-20 by the piercing member 3-30.
  • the tip of the tip portion 3-31 of the piercing member 3-30 may have a tapered structure, such as a cone or a polygonal pyramid, so that the piercing member can be significantly reduced.
  • 3-30 is the external force required to pierce the sealing film 3-20, which further facilitates the piercing of the sealing film 3-20.
  • the tip portion 3-31 of the piercing member 3-30 may be formed by a triangular face, and one side 3-311 of the triangular face is arranged in contact with the liquid outlet 3-11 is on the inner wall of the opposite pipe end and the vertex 3-312 corresponding to the side 3-311 forms the tip of the tip 3-31, which can significantly reduce the penetration of the sealing film 3-31 by the piercing member 3-30
  • the external force required at 20 o'clock further helps to pierce the sealing film 3-20.
  • the shape of the side 3-311 of the triangular surface provided on the inner wall of the end determines the shape of the tip 3-31, as shown in Figure 35(a), Figure 35(b), Figure 35(c), As shown in Figure 35(d), the side 3-311 can be arranged in a straight line, a V-shape, an arc or a U shape, so that the tip portion 3-31 can be a plane, two intersecting planes, an arc or a U shape.
  • the curved surface (as shown in Fig. 32(a), Fig. 32(b), Fig. 32(c), and Fig. 32(d) in sequence) can further improve the stability of the tip portion 3-31.
  • the angle of the apex angle 3-312 of the tip of the triangular surface forming the tip portion 3-31 may not be greater than 120 degrees, for example, it may be 10 degrees, 30 degrees, 60 degrees, 70 degrees, 80 degrees, 90 degrees, 100 degrees or 110 degrees, adopting this design can make the tip of the tip part 3-31 have a smaller volume, which can further reduce the external force required for the piercing member 3-30 to pierce the sealing film 3-20, thereby further conducive to piercing the seal
  • the film preferably, the angle of the apex angle 3-312 of the tip of the triangular surface 3-310 forming the tip portion 3-31 may not be greater than 90 degrees, for example, 5 degrees, 10 degrees, 20 degrees, 25 degrees, 40 degrees, 50 degrees, 65 degrees, 75 degrees, 85 degrees, or 90 degrees, thereby further reducing the volume of the tip of the tip portion 3-31, thereby further facilitating piercing the sealing film.
  • the thickness of the triangular surface may not be greater than 1 mm, for example, it may be 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm or 0.9 mm.
  • the contact area between the tip portion 3-31 and the sealing film 3-20 can be further reduced, and the external force required when the piercing member 3-30 pierces the sealing film 3-20 can be further reduced, thereby further facilitating the piercing of the sealing film 3- 20.
  • the thickness of the triangular surface 3-310 is gradually reduced, which can be further reduced on the basis of ensuring the tip portion 3-31 has better stability.
  • the volume of the tip of the tip portion 3-31 is further conducive to piercing the sealing membrane.
  • the piercing member 3-30 and the pipe 3-10 may be integrally formed. This not only further simplifies the structure of the microfluidic tube, but also fixes the relative position of the piercing member 3-30 and the liquid outlet 3-11 according to actual needs, ensuring that the tip 3-31 of the piercing member faces the liquid outlet 3-11, and then It is further conducive to piercing the sealing film.
  • the shape of the pipe 3-10 in the present invention is not particularly limited, and those skilled in the art can choose according to actual needs.
  • the pipe 3-10 can be cylindrical or semi-cylindrical. , Which can further facilitate pipe shaping and simplify pipe structure.
  • the pipe 3-10 may include a first plate S1 and a second elastic plate S2, and a groove 3-12 is formed on the lower surface of the first plate S1.
  • the groove 3-12 has a liquid outlet 3-11; the elastic plate S2 is arranged on the lower surface of the first plate S1 and seals the groove 3-12, so that the sealed groove 3-12 forms a micro-flow channel
  • the piercing member 3-30 is arranged in the microfluidic channel and at a position opposite to the liquid outlet 3-11, and the piercing member 3-30 is connected to the lower surface of the first plate S1 through an elastic connecting portion 3-32 and the tip portion 3-31 faces towards the liquid outlet 3-11 (the top view of the piercing member 3-30 is shown in Figure 30 and Figure 35), in which the elastic connecting portion is the elastic member, and the elastic plate S2 is squeezed by external force to make the piercing member 3-30
  • the tip portion 3-31 pierces the sealing film 3-20
  • the first plate S1 is relatively harder than the elastic plate S2, which can further facilitate the shaping of the pipe 3-10.
  • the "lower surface” in the “lower surface of the first plate” in the present invention is based on the top-to-bottom direction shown in FIGS. 36 to 39.
  • the microfluidic pipe of the above-mentioned embodiment of the present invention can be used in a fully automatic microfluidic kit, wherein the liquid outlet 3-11 can be directly facing the sample chamber of the kit, such as a lyophilized powder chamber Or reagent room, the microfluidic pipeline can be used to store diluent raw materials or pyrolysis template mixture.
  • the pipeline can be sealed without applying external force during the storage process, and when the lyophilized powder needs to be diluted, only the pipeline is required. When external force is applied to the end of 3-10, the sealing film can be pierced.
  • the microfluidic kit chip includes the microfluidic pipe described in the foregoing embodiment of the present invention. This can further simplify the structure of the microfluidic kit chip. It should be noted that the technical features and beneficial effects described above for the microfluidic pipeline are also applicable to the microfluidic kit chip, and will not be repeated here.

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Abstract

本发明公开了一种分子检测***以及适用于该分子检测***的微流控试剂盒。该分子检测***包括：基体，所述基体上设有固定装置、驱动装置、检测装置和温控装置；其中，所述固定装置适于固定含有待检测样本的容器；所述驱动装置适于驱动所述容器对所述待检测样本进行预处理；所述检测装置适于对经过所述预处理的所述待检测样本进行检测；所述温控装置适于调控所述待检测样本的温度。该微流控试剂盒包括：盒体，所述盒体内设有试剂区、样品区、反应区；微流控试剂盒芯片，该微流控试剂盒芯片包括微流控管道，该微流控管道内设有朝向液体出口的穿刺件，该微流控试剂盒芯片通过该微流控管道分别与该试剂区、该样品区和该反应区相连。

Description

分子检测*** 技术领域
本发明涉及分子生物学领域，具体而言，本发明涉及一种分子检测***。
背景技术
生物分子和其他待检物可以通过能与其反应的选择性或特异性探针进行检测。随着分子生物学的发展，对蛋白质、DNA、RNA等生物分子的检测成为疾病诊断与预测的有效手段。分子诊断技术的样品消耗少、诊断结果准确、灵敏度高、通量高等优点使得该技术在现代医学中迅速发展。
目前在分子诊断技术中，最广泛应用的检测方法是荧光标记检测技术。该技术将荧光分子基团作为标记物，通过化学修饰的途径将荧光标记物连接到探针分子或靶标分子上。检测仪器把特定波长的激光照射到待检测样本上，通过检测对应的荧光信号强度便可实现对特定分子的定量检测。然而，现有的分子检测手段仍有待改进。
发明内容
本发明是基于发明人对以下事实和问题的发现而提出的：
现有的分子检测仪器一般都不是直接对样本进行检测，而需要在检测前做大量的辅助工作。例如，需要根据样本的具体情况，对样本中的核酸进行纯化，提取所需要的分子片段，并配制相应的检测试剂，最后再把样本与检测试剂混合放置到检测仪器中进行检测。辅助工作操作繁琐且需要通过不同的仪器或工具来完成，使得分子检测必须在标准规范的实验室环境下由专业人员进行，应用场景受限，检测时间长，效率低下。
鉴于此，本发明提出一种分子检测***。该分子检测***可对待检测样本进行全自动化的快速检测。
在本发明的一个方面，本发明提出了一种分子检测***。根据本发明的实施例，该分子检测***包括：基体，所述基体上设有固定装置、驱动装置、检测装置和温控装置；其中，所述固定装置适于固定含有待检测样本的容器；所述驱动装置适于驱动所述容器对所述待检测样本进行预处理；所述检测装置适于对经过所述预处理的所述待检测样本进行检测；所述温控装置适于调控所述待检测样本的温度。
根据本发明实施例的分子检测***，将含有待检测样本的容器固定于固定装置上，在驱动装置的作用下，待检测样本在容器内流动的同时完成样本中核酸的提取和PCR反应，从而获得适于检测装置进行检测的样本。驱动装置驱动待检测样本在容器内流动的过程中，温控装置可对固定装置中的局部进行加热，从而实现样本中核酸的提取和PCR反应。在PCR反应进行的同时，检测装置可对扩增产物进行实时的荧光测量，根据荧光信号变化的数据获得检测结果。由此，本发明的分子检测***将样本核酸的纯化、提取等辅助工作整合在一台设备中，并实现了分子检测的全自动化完成，解决了传统分子检测手段受实验条件和工作人员限制而导致的应用场景有限、效率低下等问题。
另外，根据本发明上述实施例的分子检测***还可以具有如下附加的技术特征：
在本发明的一些实施例中，所述基体包括相连的第一基座、支架和轴套。
在本发明的一些实施例中，所述固定装置包括卡槽、第一电机、第一螺母、第一夹持构件、第二夹持构件和连接杆；所述第一电机通过所述第一螺母与所述第一夹持构件相连，所述第一夹持构件与所述第二夹持构件通过所述连接杆相连，所述卡槽设在所述第一夹持构件与所述第二夹持构件之间。
在本发明的一些实施例中，所述分子检测***进一步包括：第一压簧，所述第一压簧设在所述卡槽与所述第二夹持构件之间。
在本发明的一些实施例中，所述分子检测***进一步包括：第一散热组件；所述第一散热组件设在所述卡槽下方。
在本发明的一些实施例中，所述驱动装置包括第二电机、第三电机、顶针和推杆；所述第二电机与所述顶针相连，所述第三电机与所述推杆相连。
在本发明的一些实施例中，所述分子检测***进一步包括：直线导轨和滑块，所述推杆通过所述滑块设在所述直线导轨上。
在本发明的一些实施例中，所述检测装置包括光路检测单元，所述温控装置包括芯片温度循环控件。
在本发明的一些实施例中，所述检测装置的一端通过所述芯片温度循环控件与所述卡槽相连。
在本发明的一些实施例中，所述分子检测***进一步包括：控制***，所述控制***分别与所述固定装置、所述驱动装置、所述检测装置和所述温控装置相连，且适于控制所述固定装置、所述驱动装置、所述检测装置和所述温控装置协同工作以便对待检测样本进行所述检测
在本发明的一些实施例中，所述分子检测***进一步包括：滑动装置，所述滑动装置与所述驱动装置和所述固定装置相连，且适于保持所述容器位置相对固定。
在本发明的一些实施例中，所述滑动装置包括：第二基座；第一导杆，所述第一导杆可移动地插设在位于所述第二基座一端上的固定限位通孔内；第二导杆，所述第二导杆可移动地插设在位于所述第二基座另一端上的活动限位通孔内；第一连接支架，所述第一连接支架上设有第三通孔，所述第一导杆的上端和所述第二导杆的上端分别与所述第一连接支架的两端相连；第二连接支架，所述第一导杆的下端和所述第二导杆的下端分别与所述第二连接支架的两端相连；第一丝杆电机，所述第一丝杆电机设在所述第二基座上，所述第一丝杆电机中的丝杆垂直于所述第二基座并穿过所述第三通孔，所述丝杆带动所述第一连接支架移动并联动所述第一导杆、所述第二导杆和所述第二连接支架。
在本发明的一些实施例中，所述第一导杆的直径比所述固定限位通孔的内径小0.1～0.3mm，所述第二导杆的直径比所述活动限位通孔的内径小0.5～2mm。
在本发明的一些实施例中，所述第一导杆的上端和所述第二导杆的上端分别与所述第一连接支架的两端螺栓相连，所述第一导杆的下端和所述第二导杆的下端分别与所述第二连接支架的两端螺栓相连。
在本发明的一些实施例中，所述丝杆通过螺纹与所述第三通孔相连。
在本发明的一些实施例中，所述滑动装置进一步包括：第一丝杆螺母，所述第一丝杆螺母固定连接在所述第三通孔处且与所述丝杆匹配相连。
在本发明的一些实施例中，所述第一连接支架在距离所述第二基座5～55mm的区间内移动。
在本发明的一些实施例中，所述固定限位通孔和所述活动限位通孔表面均形成有润滑层。
在本发明的一些实施例中，所述润滑层为润滑油层或石墨层，所述润滑层的厚度为0.01～1mm。
在本发明的一些实施例中，所述第一丝杆电机中，丝杆为梯形丝杆、滚珠丝杆或行星滚珠丝杆，电机为直流电机、步进电机或伺服电机。
在本发明的一些实施例中，所述分子检测***进一步包括：光路成像自动调节装置，所述光路成像自动调节装置与所述检测装置相连，且包括光电传感器和凸透镜，所述光路成像自动调节装置适于自动调节所述光电传感器与所述凸透镜之间的距离。
在本发明的一些实施例中，所述光路成像自动调节装置包括：第三基座；光电传感器，所述光电传感器固定于所述第三基座上；调节支架，所述调节支架可移动地设在所述第三基座上，且所述调节支架上设有凸透镜，通过移动所述调节支架调节所述光电传感器与所述凸透镜之间的距离；第二丝杆电机，所述第二丝杆电机固定于所述第三基座上，所述第二丝杆电机中的丝杆穿过所述调节支架并带动所述调节支架移动。
在本发明的一些实施例中，所述调节支架与所述丝杆螺纹相连。
在本发明的一些实施例中，所述光路成像自动调节装置进一步包括：第二丝杆螺母，所述第二丝杆螺母与所述调节支架固定连接并与所述丝杆匹配相连。
在本发明的一些实施例中，所述调节支架的移动距离不大于30mm。
在本发明的一些实施例中，所述光电传感器与所述凸透镜之间的距离为30～60mm。
在本发明的一些实施例中，所述调节支架周壁上设有多个止抵于所述第三基座内壁的凸起。
在本发明的一些实施例中，所述第二丝杆电机与所述光电传感器通过CPU端智能联控。
在本发明的一些实施例中，所述第二丝杆电机中，丝杆为梯形丝杆、滚珠丝杆或行星滚珠丝杆，电机为直流电机、步进电机或伺服电机。
在本发明的一些实施例中，所述分子检测***中的卡槽包括：壳体，所述壳体的上部敞开且内部限定有容纳空间；定位孔，所述定位孔设在所述壳体的侧部；定位柱，所述定位柱的一端伸入所述定位孔；加热组件，所述加热组件设在所述容纳空间内；第二压簧，所述第二压簧设在所述容纳空间的底部，且与所述加热组件相连。
在本发明的一些实施例中，所述卡槽进一步包括固定螺钉，所述固定螺钉穿过所述过孔伸入所述容纳空间并与所述加热组件连接，所述第二压簧套设在所述固定螺钉上。
在本发明的一些实施例中，所述定位孔和所述定位柱均包括多个，各个所述定位孔与各个所述定位柱一一对应设置。
在本发明的一些实施例中，所述定位柱伸入所述定位孔的一端呈圆锥形。
在本发明的一些实施例中，所述加热组件包括相连的加热片和导热块，所述导热块与所述第二压簧和所述固定螺钉相连。
在本发明的一些实施例中，所述导热块上形成有加热室。
在本发明的一些实施例中，所述导热块的下部设有限位孔，所述固定螺钉伸入所述限位孔。
在本发明的一些实施例中，所述过孔的孔径大于所述固定螺钉的直径。
在本发明的另一方面，本发明提出了一种适用于上述实施例的分子检测***的微流控试剂盒。根据本发明的实施例，该微流控试剂盒包括：盒体，所述盒体内设有试剂区、样品区、反应区；微流控试剂盒芯片，所述微流控试剂盒芯片包括微流控管道，所述微流控管道内设有朝向液体出口的穿刺件，所述微流控试剂盒芯片通过所述微流控管道分别与所述试剂区、所述样品区和所述反应区相连。
本发明上述实施例的微流控试剂盒不仅可以通过微流控管道将样品区的待测样品和位于试剂区的试剂(若反应区具有冻干粉试剂，试剂区也可以存储稀释剂)引入反应区进行反应，从而实现对样品的检测，而且无需额外设置弹性阀门等外部部件来实现管路的断开与接通。
在本发明的一些实施例中，用于所述微流控试剂盒芯片的微流控管道包括：管道、密封膜和穿刺件，所述管道的端部由弹性材料形成，且液体出口设在所述端部的侧壁上；所述密封膜设在所述液体出口处并密封所述液体出口；具有尖端部的所述穿刺件设在与所述液体出口相对的所述端部的内壁上，所述尖端部朝向所述液体出口且在外力挤压所述端部时刺穿所述密封膜。由此，该微流控管道可以实现微流管道在使用前密封，使用时开封的双重功能，且在储存原料时不需要增加外部压力零件即可实现管路的密封。
在本发明的一些实施例中，所述穿刺件与所述液体出口设在所述管道的同一管径上。由此向管道端部施力时更容易刺破密封膜。
在本发明的一些实施例中，所述密封膜为锡箔纸、塑封膜或牛皮纸。由此可以有效避免微流控管道中储存的原料通过渗透作用渗出。
在本发明的一些实施例中，所述密封膜的厚度区间为0.01～0.2mm。由此不仅有利于对液体出口进行密封，还可以降低穿刺件刺穿密封膜的难度。
在本发明的一些实施例中，所述尖端部的尖端为锥形结构，所述锥形结构为圆锥或多棱锥。由此可以进一步有利于刺破密封膜。
在本发明的一些实施例中，所述尖端部由一个三角面形成，所述三角面的一边设在与所述液体出口相对的所述端部的内壁上且该边所对应的顶角形成所述尖端部的尖端。由此可以进一步有利于刺破密封膜。
在本发明的一些实施例中，所述三角面设在所述端部的内壁上的一边呈直线、V形、弧形或U形。
在本发明的一些实施例中，所述穿刺件与所述管道一体成型。由此可以进一步简化微流控管道的结构，并进一步有利于刺破密封膜。
在本发明的一些实施例中，所述管道包括第一板材和弹性板材，所述第一板材的下表面具有凹槽，所述凹槽内设有液体出口；所述弹性板材设在所述第一板材的下表面并密封所述凹槽，使得所述凹槽形成微流通道；其中，所述穿刺件设在所述微流通道内且与所述液体出口相对的位置上，且所述穿刺件通过弹性部件与所述第一板材的下表面相连，所述穿刺件在外力挤压所述弹性板材时刺穿所述密封膜。
本发明的附加方面和优点将在下面的描述中部分给出，部分将从下面的描述中变得明显，或通过本发明的实践了解到。
附图说明
附图是用来提供对本发明的进一步理解，并且构成说明书的一部分，与下面的具体实施方式一起用于解释本发明，但并不构成对本发明的限制。在附图中：
图1是根据本发明一个实施例的分子检测***的结构示意图。
图2是根据本发明一个实施例的分子检测***的结构示意图。
图3是根据本发明一个实施例的分子检测***另一视角的结构示意图。
图4是根据本发明一个实施例的分子检测***另一视角的结构示意图。
图5是根据本发明一个实施例的分子检测***另一视角的结构示意图。
图6是本发明实施例的分子检测***中固定装置、驱动装置和温控装置中部分组件的结构示意图。
图7是本发明实施例的分子检测***中检测装置中部分组件的结构示意图。
图8是本发明实施例的分子检测***中检测装置中部分组件的另一视角结构示意图。
图9是本发明实施例的分子检测***中固定装置和驱动装置中部分组件的结构示意图。
图10是本发明实施例的分子检测***中固定装置和驱动装置中部分组件的另一视角结构示意图。
图11是本发明实施例的分子检测***中固定装置和驱动装置中部分组件的另一视角结构示意图。
图12是根据本发明一个实施例的微流控试剂盒的结构示意图。
图13是根据本发明一个实施例的分子检测***中滑动装置的结构示意图。
图14是根据本发明再一个实施例的分子检测***中滑动装置的结构示意图。
图15是根据本发明一个实施例的分子检测***中的第二基座沿纵向方向的截面图
图16是根据本发明又一个实施例的分子检测***中滑动装置的结构示意图。
图17是根据本发明又一个实施例的分子检测***中滑动装置的结构示意图。
图18是根据本发明又一个实施例的分子检测***中滑动装置的结构示意图。
图19是根据本发明一个实施例的分子检测***中光路成像自动调节装置的结构示意图。
图20是根据本发明一个实施例的分子检测***中光路成像自动调节装置的调节支架与第三基座的限位关系的结构简图。
图21是根据本发明一个实施例的分子检测***中卡槽的结构示意图；
图22是根据本发明一个实施例的分子检测***中卡槽的另一视角结构示意图；
图23是适用于本发明实施例的分子检测***中卡槽的试剂盒的结构示意图；
图24根据本发明一个实施例的分子检测***中卡槽与试剂盒配合安装的结构示意图；
图25根据本发明一个实施例的分子检测***中卡槽与试剂盒配合安装的另一视角结构示意图。
图26是根据本发明一个实施例的微流控试剂盒的结构简图。
图27是根据本发明一个实施例的微流控管道的结构简图。
图28是根据本发明一个实施例的微流控管道在垂直于管道方向的截面图。
图29是根据本发明一个实施例的微流控管道在平行于管道方向的截面图。
图30是根据本发明一个实施例的穿刺件的俯视图。
图31是根据本发明又一个实施例的微流控管道的结构简图。
图32是根据本发明又一个实施例的微流控管道的尖端部的结构简图。
图33是根据本发明又一个实施例的微流控管道在垂直于管道方向的截面图。
图34是根据本发明又一个实施例的微流控管道在平行于管道方向的截面图。
图35是根据本发明又一个实施例的穿刺件的俯视图。
图36是根据本发明一个实施例的微流控管道部分组成的立体图。
图37是根据本发明一个实施例的微流控管道的立体图。
图38是根据本发明再一个实施例的微流控管道部分组成的立体图。
图39是根据本发明再一个实施例的微流控管道的立体图。
具体实施方式
下面详细描述本发明的实施例，所述实施例的示例在附图中示出，其中自始至终相同或类似的标号表示相同或类似的元件或具有相同或类似功能的元件。下面通过参考附图描述的实施例是示例性的，旨在用于解释本发明，而不能理解为对本发明的限制。
在本发明的描述中，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发明和简化描述，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发明的限制。
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。在本发明的描述中，“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。
在本发明中，除非另有明确的规定和限定，“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发明中的具体含义。
在本发明中，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。
发明人在对分子检测仪器的研究中发现，现有的分子检测仪器一般都不是直接对样本进行检测，而需要在检测前做大量的辅助工作。例如，需要根据样本的具体情况，对样本中的核酸进行纯化，提取所需要的分子片段，并配制相应的检测试剂，最后再把样本与检测试剂混合放置到检测仪器中进行检测。辅助工作操作繁琐且需要通过不同的仪器或工具来完成，使得分子检测必须在标准规范的实验室环境下由专业人员进行，应用场景受限，检测时间长，效率低下。
鉴于此，在本发明的一个方面，本发明提出了一种分子检测***。根据本发明的实施例，参考图1，该分子检测***包括：基体100以及设在基体100上的固定装置200、驱动装置300、检测装置400和温控装置500。其中，固定装置200适于固定含有待检测样本的容器；驱动装置300适于驱动容器对待检测样本进行预处理；检测装置400适于对经过预处理的待检测样本进行检测，温控装置500适于调控待检测样本的温度。
下面参考图1～12进一步对本发明的分子检测***进行详细描述。其中，图2～5分别为不同视角下该分子检测***的结构示意图。图6详细显示了固定装置200、驱动装置300和温控装置500中部分组件的相对位置关系。图7和8分别从不同视角详细显示了检测装置400中部分组件的相对位置关系。图9～11分别从不同视角详细显示了固定装置200和驱动装置300中部分组件的相对位置关系。图12为含有待检测样本的容器的结构示意图。
基体100的具体结构并不受特别限制，只要能够为固定装置200、驱动装置300、检测装置400和温控装置500提供支撑，使各装置稳定工作即可。根据本发明的实施例，参考图2～6，基体100包括相连的第一基座1、支架2和轴套3。第一基座1、支架2和轴套3共同组成了分子检测***的支撑结构，为固定装置200、驱动装置300、检测装置400和温控装置500提供支撑。
固定装置200适于固定含有待检测样本的容器，可保证在检测过程中含有待检测样本的容器的位置相对固定，从而保证待检测样本的预处理与检测过程稳定进行。根据本发明的实施例，参考图2～6，固定装置包括卡槽6、第一电机4、第一螺母5和夹持装置8，其中，夹持装置8包括第一夹持构件81、第二夹持构件82和连接杆83；第一电机4通过第一螺母5与第一夹持构件81相连，第一夹持构件81与第二夹持构件82通过连接杆83相连，卡槽6设在第一夹持构件81与第二夹持构件82之间。如图2～6所示，卡槽6设在第一基座1上，第一电机4设在轴套3上，夹持装置8中的连接杆83穿过支架2连接第一夹持构件81和第二夹持构件82。在检测过程中，含有待检测样本的容器置于卡槽6中，随着第一电机4驱动第一螺母5运动，夹持装置8中的第一夹持构件81和第二夹持构件82可将卡槽6中的容器夹紧，从而保证在检测过程中容器的位置相对固定。
根据本发明的实施例，该分子检测***还可以进一步包括：第一压簧10。第一压簧10设在卡槽6与第二夹持构件82之间，并通过螺钉9松动连接。由此，在夹持装置8运动过程中，通过第一压簧10的作用将卡槽6中的容器夹紧。
根据本发明的实施例，该分子检测***还可以进一步包括：第一散热组件61。第一散热组件61设在卡槽6下方。具体的，第一散热组件61可安装在第一基座1上，并设置在卡槽6的下方。通过在卡槽6的下方设置第一散热组件61，可以更有利于含有待检测样本的容器的散热，从而便于温控装置调控容器温度。第一散热组件61的具体种类并不受特别限制，例如可以采用翅片式散热器、板式散热器等。
驱动装置300适于驱动含有待测样本的容器第待检测样本进行预处理。预处理包括对待测样本中核 酸的提取和PCR反应。为了方便理解，下面首先对该含有待测样本的容器结构及工作原理进行详细描述。需要说明的是，在本文中，“含有待测样本的容器”也称为“试剂盒”或“微流控试剂盒”。
参考图12，试剂盒包括样本室6-1、稀释室6-2、注射室6-3、活塞6-4、PCR室6-5、缓冲室6-6、样本密封膜6-7、稀释密封膜6-8、微流控管路6-9、样本控制阀6-10、稀释控制阀6-11、第一PCR控制阀6-12、第二PCR控制阀6-13，各单元通过微流控管路6-9连接形成一个连通的回路。
初始状态下，样本室6-1含有以冻干粉状存在的裂解原料，PCR室6-5含有以冻干粉状存在的反转录酶和PCR原料，稀释室6-2含有适当稀释液。样本室6-1和稀释室6-2与微流控管路6-9连通的部位分别用样本密封膜6-7和稀释密封膜6-8密封住，使样本室6-1的裂解原料与稀释室6-2的稀释液以及PCR室6-5的反转录酶及PCR原料相互隔绝。活塞6-4处于注射室6-3的最顶端(注射室处于活塞填满状态)。
当样本室6-1添加了样本后，微流控试剂盒开始工作。首先，通过样本密封膜6-7和稀释密封膜6-8被刺穿，从而使各室和微流孔管路之间处于连通状态。第二，关闭样本控制阀6-10、第一PCR控制阀6-12、第二PCR控制阀6-13，移动活塞6-4向外拉动到一定位置，从而使稀释室6-2的稀释液通过稀释控制阀6-11流向注射室6-3。第三，关闭稀释控制阀6-11，打开样本控制阀6-10，往复移动活塞6-4，使注射室6-3的稀释液通过样本控制阀6-10进入到样本室6-1，在往复移动活塞6-4的过程中，充分将样本室6-1的裂解冻干粉与稀释液及加入的样本混合均匀。第四，开始对样本室6-1进行加热升温到设定温度，使得样本室6-1中的样本在设定的温度下进行充***解。第五，裂解完成后，移动活塞6-4向外拉动到一定位置，从而使样本室6-1的已裂解的样本混合液通过样本控制阀6-10流向注射室6-3。第六，关闭样本控制阀6-10与稀释控制阀6-11，打开第一PCR控制阀6-12与第二PCR控制阀6-13，往复移动活塞6-4，将注射室6-3的样本混合液通过第一PCR控制阀6-12进入到PCR室6-5，在往复移动活塞6-4的过程中，充分将已裂解的样本混合液与PCR室6-5的反转录酶及PCR原料冻干粉混合均匀。第九，开始对PCR室6-5进行PCR温度加热控制，在PCR扩增中激活酶的前期恒温段，PCR室6-5中的混合液会因为高温而产生膨胀，膨胀过程中的液体溢出可经过第二PCR控制阀6-13流到缓冲室6-6中，恒温段结束后，关闭第一PCR控制阀6-12与第二PCR控制阀6-13，开始对PCR室6-5进行温度循环控制，最终完成样本中核酸的扩增。
根据本发明的实施例，参考图9～11，驱动装置300包括第二电机11、第三电机13、顶针12和推杆16；第二电机11为直线电机，第三电机13为第一丝杆电机，第二电机11直接与顶针12相连，第三电机13通过第二螺母15与推杆16相连。第二电机11和顶针12可直接安装在第一基座1上，第三电机13可通过电机支架14安装在第一基座1上。通过将含有待检测样本的试剂盒固定于卡槽6中，上述试剂盒中的样本密封膜6-7和稀释密封膜6-8位置分别与一个顶针12相对，进而通过第二电机11驱动顶针12做直线运动，可以实现样本密封膜6-7和稀释密封膜6-8的刺破，从而使试剂盒中的微流控管路连通。而第三电机13可以通过第二螺母15驱动推杆16直线运动来控制试剂盒中的活塞6-4的往复运动，从而使试剂盒中的样本在试剂盒中的微流控管路内流动。
需要说明的是，在试剂盒的微流控管路内部设置有凸起的刺穿件(附图中未示出)，该刺穿件具有尖端部。刺穿件设置在与样本密封膜6-7和稀释密封膜6-8相对的位置，且刺穿件的尖端部朝向样本密封膜6-7和稀释密封膜6-8。由此，顶针12可以在不与样本直接接触的条件下，通过挤压刺穿件来将样本密封膜6-7和稀释密封膜6-8刺破，而微流控管路始终与外部(设备)处于隔绝状态，从而有效避免了样本对设备的污染。另外，试剂盒中的PCR反应均在密封的PCR反应室中进行，不会出现传统PCR实验过程中产物通过气溶胶挥发到设备腔体内的情况。
根据本发明的实施例，如图11所示，该分子检测***还可以进一步包括：直线导轨17和滑块18， 推杆16通过滑块18设在直线导轨17上。推杆16和滑块18可通过第二螺母15来固定。由此，在第三电机13的驱动下，推杆16在直线导轨17上做直线运动，从而控制活塞6-4的伸缩。
检测装置400适于对经过预处理的所述待检测样本进行检测，温控装置500适于调控待检测样本的温度。具体的，检测装置中包括光路检测单元19，温控装置500中包括芯片温度循环控件7。在温控装置500对PCR室6-5中样本进行温度循环控制的同时，检测装置400可对PCR室6-5中的扩增产物进行实时的测量，获取扩增产物的荧光信号，由于PCR室中预先布有探针，扩增产物可以与探针进行杂交，释放出荧光基团，随着扩增产物的增加，荧光基团也随之不断增加，从而导致荧光信号不断增强，并最终到达检测装置400的灵敏度范围，使得检测到的数据发生显著的变化，通过分析软件将这种数据发生显著变化的对应扩增的循环数定义为CT值，将CT值出现在某个区域内的检测结果分别定义为阳性，其余定义为阴性，从而将荧光信号变化的数据转化为阴阳性判断的检测结果。根据本发明的一个具体示例，可通过对细菌16S rRNA的PCR反应来获得检测结果。PCR反应中采用的引物包括正向引物63f(5’-CAG GCC TAA CAC ATG CAA GTC-3’)和反向引物1387r(5’-GGG CGG TGT GTA CAA GGC-3’)。根据本发明的另一个具体示例，可通过对流感病毒FluA的PCR反应来获得检测结果。PCR反应中采用的引物包括正向引物Forward(5’-CAGAGACTTGAAGATGTTTTTGC-3’)和反向引物Reverse(5’-CTACGCTGCAGTCCTCGCTC-3’)，探针Probe(5’-CAAGACCAATCCTGTCACCTCTGA-3’)。
根据本发明的实施例，检测装置的一端通过温控装置与卡槽相连。如图7和8所示，通过将试剂盒固定在卡槽6中，试剂盒中的PCR室6-5邻近温控装置中的温度循环控件7，以便于温控装置对PCR室6-5的温度控制。
根据本发明的实施例，如图2所示，该分子检测***还包括控制***20。控制***分别与固定装置、驱动装置、检测装置和温控装置相连，且适于控制固定装置、驱动装置、检测装置和温控装置协同工作以便对待检测样本进行检测。
发明人在致力于解决双导杆在直线滑动过程中由于不平行而相互干涉的问题时意外发现，通过使双导杆中其中一个沿特定的滑动方向不变，而将另一个设置为既可沿特定的滑动方向移动又可沿垂直于该特定滑动方向的方向移动，可以使两根导杆在滑动过程中不断趋于平行，进而消除双导杆在直线滑动过程中相互干涉的问题。
滑动装置
根据本发明的实施例，本发明的分子检测***还进一步包括滑动装置，该滑动装置与驱动装置和固定装置相连，且适于保持所述容器位置相对固定。参考图13，滑动装置包括第二基座13-10、第一导杆13-20、第二导杆13-30、第一连接支架13-40、第二连接支架13-50和第一丝杆电机13-60。其中，第二基座13-10一端设有固定限位通孔13-11，另一端设有活动限位通孔13-12；第一导杆13-20可移动地插设在固定限位通孔13-11内；第二导杆13-30可移动地插设在活动限位通孔13-12内；第一连接支架13-40上具有第三通孔13-41，第一连接支架13-40的两端分别与第一导杆13-20和第二导杆13-30的上端相连；第二连接支架13-50的两端分别与第一导杆13-20和第二导杆13-30的下端相连；第一丝杆电机13-60设在第二基座13-10上并使第一丝杆电机13-60上的丝杆13-61与第二基座13-10垂直，且丝杆13-61穿过第三通孔13-41并带动第一连接支架13-40移动并联动第一导杆13-20、第二导杆13-30和第二连接支架13-50。当第一丝杆电机13-60的丝杆13-61转动时，将带动第一连接支架13-40随丝杆13-61运动，同时第一支架13-40带动第一导杆13-20、第二导杆13-30和第二连接支架13-50运动，此时，第一导杆13-20在活动过程中沿固定限位通孔13-11滑动，固定限位通孔13-11使第一导杆13-20沿第二基座13-10纵向方向滑动且保持滑动方向基本不变，而第二导杆13-30在活动限位通孔13-12中滑动，活动限位通孔13-12可以在第二基座13-10横向方向上为第二导杆13-30提供的一定的活动空间，使第二导杆13-30在随第一 支架13-40运动时在第二基座13-10内可通过的空间变大，从而即便在安装过程中不能确保第一导杆13-20和第二导杆13-30平行，在第一导杆13-20的运动方向基本不变的基础上，也可以借助活动限位通孔13-12使第二导杆13-30在不改变其原有固定方向的前提下在第二基座通孔内顺畅滑动，从而有效避免导杆在运动过程中受到第二基座13-10的干涉。综上所述，该滑动装置不仅结构简单且导杆易于安装，还可以在双导杆不平行的情况下使双导杆在第二基座13-10通孔内顺畅滑动。需要说明的是，本发明中所述的“横向”如附图13所示，“纵向”为垂直于该“横向”的方向，“上端”和下端是基于附图13中从下往上的方向而言的。
根据本发明的一个具体实施例，固定限位通孔13-11的内径大于第一导杆13-20直径0.1～0.3mm。发明人发现，若固定限位通孔13-11的内径与第一导杆13-20直径的差值过大，第一导杆13-20在沿第二基座13-10纵向方向滑动时也会沿第二基座13-10横向方向滑动，不仅不能有效固定第一导杆13-20的滑动方向，同时还会导致第一连接支架13-40、第二连接支架13-50和第二导杆13-20的整体滑动方向也不断变化，从而引起导杆在第二基座13-10上的窜动，大大降低了导杆在第二基座13-10上滑动的平稳性；而若固定限位通孔13-11的内径与第一导杆13-20直径的差值过小时，又会增加第一导杆13-20沿第二基座13-10纵向方向滑动的难度。本发明中通过控制固定限位通孔13-11的内径大于第一导杆13-20直径0.1～0.3mm，不仅可以使第一导杆13-20在第二基座13-10内顺畅滑动，还可以确保第一导杆13-20在滑动过程中的滑动方向基本不变。
根据本发明的再一个具体实施例，活动限位通孔13-12的内径大于第二导杆13-30直径为0.5～2mm。实际上，本发明上述实施例的滑动装置中，双导杆与连接支架固定好后，即便第一导杆13-20和第二导杆13-30不平行时，二者在滑动过程中第二导杆13-30的运动方向实际上也是基本保持不变的，仅是由于第一导杆13-20和第二导杆13-30不平行而导致二者通过第二基座13-10时在第二基座13-10横向方向上的距离不断发生变化，而发明人发现，若活动限位通孔13-12的内径与第二导杆13-30直径的差值过小，不足以消除第二基座13-10对导杆运动的干涉问题，而若活动限位通孔13-12的内径与第二导杆13-30直径的差值过大，又不能确保导杆的平稳运行。本发明中通过控制活动限位通孔13-12的内径大于第二导杆直径0.5～2mm，不仅可以消除由于双导杆不平行而产生的干涉问题，使双导杆在不平行的情况下也可以在第二基座13-10通孔内顺畅滑动，同时还可以确保导杆运动平稳。
根据本发明的又一个具体实施例，活动限位通孔13-12在沿第二基座13-10纵向方向上的截面可以为圆形、椭圆形或胶囊形，活动限位通孔13-12的内径大于第二导杆13-30直径0.5～2mm，由此可以在沿第二基座13-10横向方向为第二导杆13-30提供足够的活动空间。当活动限位通孔13-12在沿第二基座13-10纵向方向上的截面为椭圆形或胶囊形时，为椭圆时椭圆的长轴可以平行于活动限位通孔13-12到固定限位通孔13-11的方向，为胶囊形时(如图15所示)胶囊形的长度方向可以平行于活动限位通孔13-12向固定限位通孔13-11的方向，且胶囊形的宽度可以与固定限位通孔13-11的内径相同，由此，不仅可以消除由于双导杆不平行而产生的干涉问题，使双导杆在不平行的情况下也可以在第二基座13-10通孔内顺畅滑动，同时还可以进一步确保导杆平稳运动。
根据本发明的又一个具体实施例，如图16所示，第二基座13-10上可以进一步包括固定轴套13-13和活动轴套13-14，固定轴套13-13固定在固定限位通孔13-11内，第一导杆13-20穿过固定轴套13-13滑动；活动轴套13-14轴套固定在活动限位通孔13-12内，且活动轴套13-14轴套外设有滑动件13-15，第二基座13-10内设有与滑动件13-15相匹配的滑动轨道13-16，滑动轨道13-16使活动轴套13-14可以沿第二基座13-10纵向和横向方向移动。由此，可以在确保双导杆在不平行的情况下也可以在第二基座13-10内顺畅滑动的基础上进一步确保导杆平稳运动。
根据本发明的又一个具体实施例，第一连接支架13-40的两端分别与第一导杆13-20和第二导杆 13-30的上端螺栓相连，第二连接支架13-50的两端分别与第一导杆13-20和第二导杆13-30的下端螺栓相连。
根据本发明的又一个具体实施例，丝杆13-61与第三通孔13-41的固定方式并不受特别限制，本领域技术人员可以根据实际需要进行选择。例如，丝杆13-61与第三通孔13-41可以通过螺纹相连，由此，无需设置固定螺母，丝杆13-61与第三通孔13-41通过螺纹直接连接即可使丝杆13-61与第一连接支架13-40相对固定，从而在丝杆13-61转动时可以带动第一连接支架13-40沿丝杆方向运动并联动第一导杆13-20、第二导杆13-30和第二连接支架13-50。
根据本发明的又一个具体实施例，参考图14，上述滑动装置可以进一步包括：第一丝杆螺母13-70，第一丝杆螺母13-70与丝杆13-61匹配相连且与第三通孔13-41固定连接。由此，可以进一步提高丝杆13-61和第一连接支架13-40的固定强度，进而有效防止由于第一连接支架13-40与丝杆13-61连接松动而出现异常运动的问题。
根据本发明的又一个具体实施例，上述滑动装置应用于分子检测***，以便自动控制试剂盒的压紧固定或松开，此时，第一连接支架13-40距离第二基座13-10的移动范围为5～55mm。由此可以便于试剂盒的固定或更换，提高检测效率。
根据本发明的又一个具体实施例，本发明的第一丝杆电机13-50中电机及丝杆13-51的类型一般不受限制，本领域技术人员可以根据实际需要进行选则。例如，电机可以为直流电机、步进电机或伺服电机，丝杆13-51可以为梯形丝杆、滚珠丝杆或行星滚珠丝杆。由此可以进一步提高本发明的适用性。
根据本发明的又一个具体实施例，如图17和图18所示，固定限位通孔13-11和活动限位通孔13-12表面均形成有润滑层13-80，由此可以进一步减小第一导杆和第二导杆在滑动过程中与第二基座之间可能产生的摩擦和磨损，进而进一步降低第二基座对导杆的干涉。需要说明的是，本发明中润滑层13-80的材料并不受特别限制，本领域技术人员可以根据实际需要进行选择。例如，润滑层80可以由液体润滑剂、半固体润滑剂或固体润滑剂形成，由此可以有效降低双导杆和第二基座13-10之间可能产生的摩擦和磨损。
根据本发明的又一个具体实施例，润滑层13-80可以为润滑油层或石墨层，由此，不仅可以确保润滑层80在常温下也具有较好的润滑性能，还可以防止限位通孔生锈，从而可以进一步避免导杆在运动过程中受第二基座干涉的现象。进一步地，润滑层13-80的厚度可以为0.01～1mm，例如0.05～0.5mm、0.1mm、0.2mm、0.3mm、0.4mm、0.5mm、0.6mm、0.7mm、0.8mm或0.9mm等。由此可以进一步避免导杆在运动过程中受第二基座干涉的现象。
另外，在本发明的另一方面，本发明还提出一种滑动装置，本领域技术人员能够理解的是，该滑动装置具有上文针对滑动装置所描述的全部特征和优点，在此不再一一赘述。
光路成像自动调节装置
根据本发明的实施例，本发明的分子检测***还可以包括：光路成像自动调节装置，该光路成像自动调节装置与所述检测装置相连，且包括光电传感器和凸透镜，所述光路成像自动调节装置适于自动调节所述光电传感器与所述凸透镜之间的距离。该光路成像自动调节装置中，当第二丝杆电机的丝杆转动时，将带动调节支架随丝杆运动，而凸透镜设置在调节支架上，因而调节支架运动的同时又会带动凸透镜运动，使凸透镜沿丝杆方向往复运动，从而改变凸透镜到光电传感器的相对距离，进而改变凸透镜的成像位置，最终使凸透镜的成像刚好落在光电传感器的接收区域，实现成像的自动调节。由此，该光路成像自动调节装置不仅可以实现在光路***中对不同物距待测物(即检测样本)的检测还可获得最佳最清晰的图像。
根据本发明的实施例，如图19所示，上述光路成像自动调节装置包括第三基座19-10、光电传感器 19-20、调节支架19-30、凸透镜19-40和第二丝杆电机19-50。其中，光电传感器19-20固定在第三基座19-10上；调节支架19-30可移动地设置在第三基座19-10上；凸透镜19-40设置在调节支架19-30上且可通过移动调节支架19-30调节凸透镜19-40与光电传感器19-20之间的距离；第二丝杆电机19-50固定在第三基座19-10上且使第二丝杆电机19-50上的丝杆19-51穿过调节支架19-30并带动调节支架19-30移动。该光路成像自动调节装置中，当第二丝杆电机19-50的丝杆19-51转动时，将带动调节支架19-30随丝杆19-51运动，而凸透镜19-40设置在调节支架19-30上，因而调节支架19-30运动的同时又会带动凸透镜19-40运动，使凸透镜19-40沿丝杆19-51方向往复运动，从而改变凸透镜19-40到光电传感器19-20的相对距离，进而改变凸透镜19-40的成像位置，最终使凸透镜19-40的成像刚好落在光电传感器19-20的接收区域，实现成像的自动调节。由此，该光路成像自动调节装置不仅可以实现在光路***中对不同物距待测物(即检测样本)的检测还可获得最佳最清晰的图像。
根据本发明的一个具体实施例，本发明中丝杆19-51与调节支架19-30的固定方式并不受特别限制，本领域技术人员可以根据实际需要进行选择。例如，丝杆19-51与调节支架19-30之间通过螺纹相连，由此可以使丝杆19-51与调节支架19-30相对固定，并提高二者的固定强度，从而在丝杆19-51转动时可以带动调节之间沿丝杆19-51方向运动，进而变凸透镜19-40到光电传感器19-20的相对距离。
根据本发明的再一个具体实施例，光路成像自动调节装置可以进一步包括：第二丝杆螺母19-60，第二丝杆螺母19-60与丝杆19-51匹配相连且与调节支架19-30固定连接。由此可以进一步提高丝杆19-51和调节支架19-30的固定强度，并有效防止由于调节支架19-30与丝杆19-51连接松动而出现异常运动的问题。
根据本发明的又一个具体实施例，本发明中所述的光路成像自动调节装置可以应用于分子自动检测***，以便获得最佳最清晰的图像，此时，调节支架19-30可移动的最大距离为30mm，例如调节支架19-30的移动距离可以5mm、10mm、15mm、20mm或25mm等。由此，可以通过调节支架19-30控制凸透镜19-40与光电传感器19-20之间的距离，使二者之间的距离在30～60mm范围内变化，由此可以进一步有利于获得最佳最清晰的图像。
根据本发明的又一个具体实施例，如图20所示，调节支架19-30周壁上形成有多个凸起筋19-31，凸起筋19-31止抵于第三基座19-10内壁。本发明中通过采用上述设置可以有效减少调节支架19-30与第三基座19-10的接触面积，进而减小调节支架19-30与第三基座19-10在相互移动过程中所产生的摩擦。根据本发明的又一个具体实施例，光电传感器19-20可以与第二丝杆电机19-50通过CPU端智能联控。本发明通过采用上述设置，可以根据所获得图像的清晰度对控制第二丝杆电机的启动或停止，以便获得最佳最清晰的图像。具体地，当所获得的图像不清晰时，CPU端控制第二丝杆电机19-50开启，通过丝杆19-51转动不断调节凸透镜19-40与光电传感器19-20之间的距离，直至获得最清晰的图像，当获得的图像清晰度达到要求时，CPU端控制第二丝杆电机19-50停止工作。由此，可以进一步实现在光路***中对不同物距待测物的检测还可获得最佳最清晰的图像。
根据本发明的又一个具体实施例，本发明的第二丝杆电机19-50中电机及丝杆19-51的类型一般不受限制，本领域技术人员可以根据实际需要进行选则。例如，电机可以为直流电机、步进电机或伺服电机，丝杆19-51可以为梯形丝杆、滚珠丝杆或行星滚珠丝杆。由此可以进一步提高本发明的适用性。
另外，在本发明的另一方面，本发明还提出一种光路成像自动调节装置，本领域技术人员能够理解的是，该光路成像自动调节装置具有上文针对光路成像自动调节装置所描述的全部特征和优点，在此不再一一赘述。
卡槽
根据本发明的实施例，参考图21和图23，本发明提出的分子检测***中的卡槽包括：壳体2-100、 定位孔2-200、定位柱2-300、加热组件2-400和第二压簧2-500。其中，壳体2-100的上部敞开且内部限定有容纳空间2-110；定位孔2-200设在壳体2-100的侧部；定位柱2-300的一端伸入定位孔2-200；加热组件2-400设在容纳空间2-110内；第二压簧2-500设在容纳空间2-110的底部，且与加热组件2-400相连。
利用上述卡槽，将试剂盒放入壳体容纳空间后，试剂盒的待加热部位可自然落在加热组件上，且试剂盒上用于定位的开口(预先加工得到的定位口)位于略微高于试剂盒卡槽定位孔的位置。通过将定位柱沿定位孔向试剂盒的方向移动，在定位柱卡入定位口的过程中，试剂盒也将略微向下移动，并使第二压簧产生压缩变形。在定位柱与第二压簧的协同作用下，试剂盒的待加热部位可与卡槽中的加热组件紧密贴合。由此，利用本发明的卡槽对试剂盒进行固定和加热，对试剂盒的加工要求只需满足待加热部位配合加热组件、定位口配合定位柱即可，从而大大降低了试剂盒的加工成本，且试剂盒待加热部位与加热组件贴合紧密稳定，可以满足实验中的试剂盒加热要求。
根据本发明的实施例，参考图21和22，壳体2-100的底部还设有过孔2-120，卡槽进一步包括固定螺钉2-600，固定螺钉2-600穿过过孔2-120伸入容纳空间2-110并与加热组件2-400连接，第二压簧2-500套设在固定螺钉2-600上。通过将加热组件2-400和第二压簧2-500安装在固定螺钉2-600上，可以进一步便于加热组件2-400和第二压簧2-500在壳体容纳空间2-110中的安装，并进一步提高加热组件2-400和第二压簧2-500安装的稳定性。试剂盒放入容纳空间2-110后，其待加热部位可自然落在加热组件2-400上，并将第二压簧2-500在固定螺钉2-600上略微下压。
根据本发明的实施例，定位孔2-200和定位柱2-300均可包括多个，且各个定位孔2-200与各个定位柱2-300一一对应设置，也即是说，每一个定位孔2-200中***一个定位柱2-300。通过设置多个定位孔2-200和定位柱2-300，一方面可以进一步便于利用定位柱2-300来将待固定的试剂盒下压，使其待加热部位与加热组件2-400紧密贴合；另一方面还可以进一步提高试剂盒固定后的稳定性，避免试剂盒在实验中发生位移。根据本发明的一个具体示例，如图21、22和24所示，在壳体2-100的一个侧壁的两侧可分别设置两组定位孔2-200和定位柱2-300。由此，可进一步便于利用定位柱2-300来将待固定的试剂盒下压，使其待加热部位与加热组件2-400紧密贴合，并进一步提高试剂盒固定后的稳定性。
根据本发明的实施例，参考图21和24，定位柱2-300伸入定位孔2-200的一端呈圆锥形，换言之，沿定位柱2-300伸入定位孔2-200的方向，定位柱2-300的横截面积逐渐减小定位柱，定位柱2-300的头部呈锥角变化。通过将定位柱2-300伸入定位孔2-200的一端设置为呈圆锥形，可以更便于定位柱2-300在卡入试剂盒相应地定位口的过程中将试剂盒下压。
根据本发明的实施例，加热组件2-400包括相连的加热片2-410和导热块2-420，其中导热块2-420与第二压簧2-500相连。根据本发明的具体示例，如图21、22、24和25所示，加热片2-410可设在导热块2-420的一侧。在工作中，可控制加热片2-410发热，并利用加热片2-410间接地将导热块2-420加热。由此，导热块2-420整体的温度相对均匀，从而可以进一步改善对试剂盒中待加热部位的加热效果。
根据本发明的实施例，如图22所示，导热块2-420上可形成有加热室2-421。需要说明的是，加热室2-421的具体形状并不受特别限制，加热室2-421可以根据试剂盒待加热部位的形状加工成与之相配合的形状，以便于试剂盒待加热部位与加热室2-421紧密贴合。
根据本发明的实施例，如图22所示，导热块2-420的下部设有限位孔2-422，固定螺钉2-600可伸入限位孔2-422中。由此，可进一步便于导热块与固定螺钉2-600的连接。根据本发明的一个具体示例，固定螺钉2-600与导热块2-420通过限位孔2-422螺纹连接。
根据本发明的实施例，过孔2-120的孔径大于固定螺钉2-600的直径。由此，固定螺钉2-600更容易穿过过孔2-120可在壳体2-100的一定范围内的任意方向移动，并使得加热模块2-400既可以在一定范围 内随着固定螺钉2-600移动，又受到第二压簧2-500变形产生的压力，从而与试剂盒的待加热部位紧密贴合。
为了方便理解，下面参考图23～25对本发明的卡槽与试剂盒的安装配合关系进行详细描述。
适用于本发明卡槽的试剂盒结构如图23所示，其中，试剂盒2-700包括待加热部位2-710和定位口2-720。通过采用本发明的卡槽，在试剂盒上加工得到定位口2-720即可与卡槽稳定固定。根据本发明的具体示例，试剂盒2-700可包括两个定位口2-720，其中，一个定位口2-720为圆形孔，另一个定位口2-720为腰形孔。由此，可进一步扩大试剂盒2-700在卡槽中可移动的自由度，从而进一步保证试剂盒2-700通过定位柱2-300和第二压簧2-500固定的稳定性，使试剂盒2-700的待加热部位2-710紧密贴合在导热块2-420的加热室2-421中。
参考图24，试剂盒2-700从卡槽的上方放入后，待加热部位2-710进入加热室2-421中，两定位口2-720分别与定位孔2-200和定位柱2-300相对。通过控制定位柱2-300沿定位孔2-200向试剂盒2-700的方向移动，定位柱2-300卡入定位口2-720。在定位柱2-300卡入定位口2-720的过程中，定位柱2-300的圆锥形头部通过定位口2-720带动试剂盒2-700向下移动，并使第二压簧2-500进一步地压缩。同时，固定螺钉2-600也可以带动导热块2-420在一定范围内自由移动。完成固定后，如图25所示，在定位柱2-300和第二压簧2-500的协同作用下，试剂盒2-700的待加热部位可以紧密贴合在导热块2-420的加热室2-421中。
综上可知，本发明提出的分子检测***通过采用上述实施例的卡槽来对试剂盒进行固定和加热，对试剂盒的加工要求低，且试剂盒待加热部位与加热组件贴合紧密稳定，可以满足实验中的试剂盒加热要求。
另外，在本发明的另一方面，本发明还提出一种卡槽，本领域技术人员能够理解的是，该卡槽具有上文针对卡槽所描述的全部特征和优点，在此不再一一赘述。
在本发明的另一方面，本发明提出了一种适用于上述实施例的分子检测***的微流控试剂盒。根据本发明的实施例，如图26和图27所示，该微流控试剂盒包括：盒体3-200和微流控试剂盒芯片3-100，盒体3-200内设有试剂区3-210、样品区3-220、反应区3-230；微流控试剂盒芯片3-100包括微流控管道3-110，微流控管道3-110内设有朝向液体出口3-11的穿刺件3-30，微流控试剂盒芯片3-100通过微流控管道3-110分别与试剂区3-210、样品区3-220和反应区3-230相连。该微流控试剂盒不仅可以通过微流控管道将样品区的待测样品和位于试剂区的试剂(若反应区具有冻干粉试剂，试剂区也可以存储稀释剂)引入反应区进行反应，从而实现对样品的检测，而且无需额外设置弹性阀门等外部部件来实现管路的断开与接通。
根据本发明的实施例，如图27所示，用于微流控试剂盒芯片3-100的微流控管道3-110包括管道3-10、密封膜3-20和穿刺件3-30。其中，管道3-10的端部由弹性材料形成，且端部的侧壁上具有液体出口3-11；密封膜3-20设置在液体出口3-11处以便对液体出口3-11进行密封；穿刺件3-30具有尖端部3-31，穿刺件3-30设置在与液体出口3-11相对的端部的内壁上且使尖端部3-31朝向液体出口3-11，当在外力挤压端部时使尖端部3-31刺穿密封膜3-20。该微流控管道通过在管道3-10的液体出口3-11处设置密封膜3-20进行密封，并在与液体出口3-11相对的管道3-10端部的内壁上设置具有尖端部3-31的穿刺件3-30且使尖端部3-31朝向液体出口3-11，可以使微流控管道在使用前处于密封状态，而在使用时可以预先向管道3-10端部施力，从而使穿刺件3-30刺穿密封膜。由此，该微流控管道中存储原料时无需增加外部压力零件即可实现管路的密封，简化了微流控管道使用时的操作步骤。需要说明的是，本发明中所述的管道3-10端部指的是微流控管道邻近液体出口的一端，另外穿刺件又叫做刺穿件，液体出口又叫出液口。
根据本发明的一个具体实施例，穿刺件3-30与液体出口3-11可以位于管道3-10的同一管径上。由 此，可以使穿刺件3-30正对位于液体出口部位的密封膜3-20，进而对管道3-10端部施力时可以更有利于穿刺件尖端部3-31刺破密封膜3-20。
根据本发明的再一个具体实施例，本发明中，穿刺件尖端部3-31与密封膜3-20之间距离并不受特别限制，本领域技术人员可以根据微流控管道的实际规格和需要进行选择，例如，穿刺件尖端部3-31与密封膜3-20之间距离可以为0.05～4mm，或0.05～2mm、0.05～1mm等。由此，不仅可以确保管道3-10端部不受外力时穿刺件3-30不会刺破密封膜3-20，即确保微流控管道在储存原料过程中处于密封状态，而且在对管道3-10端部施力时还可以确保密封膜3-20能够被刺破，进而使微流控管道储存的原料从液体出口3-11渗出。
根据本发明的又一个具体实施例，密封膜3-20可以为锡箔纸、塑封膜或牛皮纸等不具有渗透作用的膜材料。由此可以有效避免微流控管道中储存的原料在管道3-10处于密封状态时通过渗透作用渗出。
根据本发明的又一个具体实施例，密封膜3-20的厚度可以为0.01～0.2mm。发明人发现，若密封膜3-20的厚度过小，密封膜容易被破坏，增加了密封膜3-20对液体出口3-11的密封难度，而若密封膜3-20的厚度过大，又会增加刺破密封膜3-20的难度。本发明中通过控制密封膜3-20的厚度为0.01～0.2mm，不仅有利于对液体出口3-11进行密封，还可以降低穿刺件3-30刺穿密封膜3-20的难度。
根据本发明的又一个具体实施例，如图27-29所示，穿刺件3-30的尖端部3-31的尖端可以呈锥形结构，例如圆锥或多棱锥，由此可以显著降低穿刺件3-30刺破密封膜3-20时所需的外力，进而进一步有利于刺破密封膜3-20。
根据本发明的又一个具体实施例，如图31-35所示，穿刺件3-30的尖端部3-31可以由一个三角面形成，所述三角面的一边3-311设在与液体出口3-11相对的管道端部的内壁上且该边3-311所对应的顶角3-312形成尖端部3-31的尖端，由此可以显著降低穿刺件3-30刺破密封膜3-20时所需的外力，进而进一步有利于刺破密封膜3-20。进一步地，该三角面设在所述端部的内壁上的一边3-311的形状决定尖端部3-31的形状，如图35(a)、图35(b)、图35(c)、图35(d)所示，该边3-311可以呈直线、V形、弧形或U形布置，由此可以使尖端部3-31呈平面、两个相交的平面、弧面或U形弧面(依次如图32(a)、图32(b)、图32(c)、图32(d)所示)，进而可以进一步提高尖端部3-31的稳定性。另外，三角面形成尖端部3-31的尖端的顶角3-312的角度可以不大于120度，例如可以为10度、30度、60度、70度、80度、90度、100度或110度，采用该设计可以使尖端部3-31的尖端具有较小的体积，由此可以进一步降低穿刺件3-30刺破密封膜3-20所需的外力，从而进一步有利于刺破密封膜；优选地，三角面3-310形成尖端部3-31的尖端的顶角3-312的角度可以不大于90度，例如可以为5度、10度、20度、25度、40度、50度、65度、75度、85度或90度，由此可以进一步降低尖端部3-31尖端的体积，从而进一步有利于刺破密封膜。
根据本发明的又一个具体实施例，三角面的厚度可以不大于1mm，例如可以为0.1mm、0.2mm、0.3mm、0.4mm、0.5mm、0.6mm、0.7mm、0.8mm或0.9mm等。由此可以进一步缩小尖端部3-31与密封膜3-20的接触面积，进一步降低穿刺件3-30刺破密封膜3-20时所需的外力，从而进一步有利于刺破密封膜3-20。优选地，沿尖端部3-31朝向液体出口3-11的方向上，三角面3-310的厚度逐渐变小，由此可以在确保尖端部3-31具有较好稳定性的基础上进一步降低尖端部3-31尖端的体积，从而进一步有利于刺破密封膜。
根据本发明的又一个具体实施例，如图28、图29、图33和图34所示，穿刺件3-30与管道3-10可以一体成型。由此不仅可以进一步简化微流控管道的结构，还可以根据实际需要固定穿刺件3-30和液体出口3-11的相对位置，确保穿刺件尖端部3-31朝向液体出口3-11，进而进一步有利于刺破密封膜。
根据本发明的又一个具体实施例，本发明中管道3-10的形状并不受特别限制，本领域技术人员可以 根据实际需要进行选择，例如，管道3-10可以为圆柱形或半圆柱形，可以进一步有利于管道成型并简化管道结构。
根据本发明的又一个具体实施例，如图36和图37所示，管道3-10可以包括第一板材S1和第二弹性板材S2，第一板材S1的下表面形成有凹槽3-12，凹槽3-12内具有液体出口3-11；弹性板材S2设置在第一板材S1的下表面，并对凹槽3-12进行密封，使得密封后的凹槽3-12形成微流通道；其中，穿刺件3-30设置在微流通道内且与液体出口3-11相对的位置上，穿刺件3-30通过弹性连接部3-32连接在第一板材S1的下表面上且尖端部3-31朝向液体出口3-11(穿刺件3-30的俯视图如图30和图35所示)，其中弹性连接部即为弹性部件，通过外力挤压弹性板材S2使得穿刺件3-30的尖端部3-31刺穿密封膜3-20，如图38和图39所示。由此不仅更有利于管道3-10成型，还进一步有利于密封膜3-20被刺穿。优选地，第一板材S1相对弹性板材S2较硬，由此可以进一步有利于管道3-10成型。需要说明的是，本发明中所述“第一板材的下表面”中的“下表面”是基于附图36～39中所示的从上到下的方向而言的。
根据本发明的又一个具体实施例，本发明上述实施例的微流控管道可以用于全自动微流控试剂盒，其中液体出口3-11可以正对试剂盒的样本室如冻干粉室或试剂室，微流控管道可以用于存储稀释剂原料或裂解样板混合液，存储过程中不需要施加外力即可实现管道的密封，而当需要对冻干粉进行稀释时，仅需对管道3-10端部施加外力时密封膜被刺破即可实现。
根据本发明的实施例，微流控试剂盒芯片包括本发明上述实施例所述的微流控管道。由此可以进一步简化微流控试剂盒芯片的结构。需要说明的是，上述针对微流控管道所描述的技术特征和有益效果同样适用于该微流控试剂盒芯片，此处不再赘述。
在本说明书的描述中，参考术语“一个实施例”、“一些实施例”、“示例”、“具体示例”、或“一些示例”等的描述意指结合该实施例或示例描述的具体特征、结构、材料或者特点包含于本发明的至少一个实施例或示例中。在本说明书中，对上述术语的示意性表述不必须针对的是相同的实施例或示例。而且，描述的具体特征、结构、材料或者特点可以在任一个或多个实施例或示例中以合适的方式结合。此外，在不相互矛盾的情况下，本领域的技术人员可以将本说明书中描述的不同实施例或示例以及不同实施例或示例的特征进行结合和组合。
尽管上面已经示出和描述了本发明的实施例，可以理解的是，上述实施例是示例性的，不能理解为对本发明的限制，本领域的普通技术人员在本发明的范围内可以对上述实施例进行变化、修改、替换和变型。

Claims (47)

  1. 一种分子检测***，其特征在于，包括：
    基体，所述基体上设有固定装置、驱动装置、检测装置和温控装置；
    其中，
    所述固定装置适于固定含有待检测样本的容器；
    所述驱动装置适于驱动所述容器对所述待检测样本进行预处理；
    所述检测装置适于对经过所述预处理的所述待检测样本进行检测；
    所述温控装置适于调控所述待检测样本的温度。
  2. 根据权利要求1所述的分子检测***，其特征在于，所述基体包括相连的第一基座、支架和轴套。
  3. 根据权利要求2所述的分子检测***，其特征在于，所述固定装置包括卡槽、第一电机、第一螺母、第一夹持构件、第二夹持构件和连接杆；所述第一电机通过所述第一螺母与所述第一夹持构件相连，所述第一夹持构件与所述第二夹持构件通过所述连接杆相连，所述卡槽设在所述第一夹持构件与所述第二夹持构件之间。
  4. 根据权利要求3所述的分子检测***，其特征在于，进一步包括：第一压簧，所述第一压簧设在所述卡槽与所述第二夹持构件之间。
  5. 根据权利要求3或4所述的分子检测***，其特征在于，进一步包括：第一散热组件；所述第一散热组件设在所述卡槽下方。
  6. 根据权利要求2所述的分子检测***，其特征在于，所述驱动装置包括第二电机、第三电机、顶针和推杆；所述第二电机与所述顶针相连，所述第三电机与所述推杆相连。
  7. 根据权利要求6所述的分子检测***，其特征在于，进一步包括：直线导轨和滑块，所述推杆通过所述滑块设在所述直线导轨上。
  8. 根据权利要求3所述的分子检测***，其特征在于，所述检测装置包括光路检测单元，所述温控装置包括芯片温度循环控件。
  9. 根据权利要求8所述的分子检测***，其特征在于，所述检测装置的一端通过所述芯片温度循环控件与所述卡槽相连。
  10. 根据权利要求2所述的分子检测***，其特征在于，进一步包括：控制***，所述控制***分别与所述固定装置、所述驱动装置、所述检测装置和所述温控装置相连，且适于控制所述固定装置、所述驱动装置、所述检测装置和所述温控装置协同工作以便对待检测样本进行所述检测。
  11. 根据权利要求1～10任一项所述的分子检测***，其特征在于，进一步包括：
    滑动装置，所述滑动装置与所述驱动装置和所述固定装置相连，且适于保持所述容器位置相对固定。
  12. 根据权利要求11所述的分子检测***，其特征在于，所述滑动装置包括：
    第二基座；
    第一导杆，所述第一导杆可移动地插设在位于所述第二基座一端上的固定限位通孔内；
    第二导杆，所述第二导杆可移动地插设在位于所述第二基座另一端上的活动限位通孔内；
    第一连接支架，所述第一连接支架上设有第三通孔，所述第一导杆的上端和所述第二导杆的上端分别与所述第一连接支架的两端相连；
    第二连接支架，所述第一导杆的下端和所述第二导杆的下端分别与所述第二连接支架的两端相连；
    第一丝杆电机，所述第一丝杆电机设在所述第二基座上，所述第一丝杆电机中的丝杆垂直于所述第二基座并穿过所述第三通孔，所述丝杆带动所述第一连接支架移动并联动所述第一导杆、所述第二导杆 和所述第二连接支架。
  13. 根据权利要求12所述的分子检测***，其特征在于，所述第一导杆的直径比所述固定限位通孔的内径小0.1-0.3mm，所述第二导杆的直径比所述活动限位通孔的内径小0.5-2mm。
  14. 根据权利要求12所述的分子检测***，其特征在于，所述第一导杆的上端和所述第二导杆的上端分别与所述第一连接支架的两端螺栓相连，所述第一导杆的下端和所述第二导杆的下端分别与所述第二连接支架的两端螺栓相连。
  15. 根据权利要求12所述的分子检测***，其特征在于，所述丝杆通过螺纹与所述第三通孔相连。
  16. 根据权利要求15所述的分子检测***，其特征在于，进一步包括：
    第一丝杆螺母，所述第一丝杆螺母固定连接在所述第三通孔处且与所述丝杆匹配相连。
  17. 根据权利要求16所述的分子检测***，其特征在于，所述第一连接支架在距离所述第二基座5～55mm的区间内移动。
  18. 根据权利要求12所述的分子检测***，其特征在于，所述固定限位通孔和所述活动限位通孔表面均形成有润滑层。
  19. 根据权利要求18所述的分子检测***，其特征在于，所述润滑层为润滑油层或石墨层，所述润滑层的厚度为0.01～1mm。
  20. 根据权利要求12～19任一项所述的分子检测***，其特征在于，所述第一丝杆电机中，丝杆为梯形丝杆、滚珠丝杆或行星滚珠丝杆，电机为直流电机、步进电机或伺服电机。
  21. 根据权利要求1～10任一项所述的分子检测***，其特征在于，进一步包括：
    光路成像自动调节装置，所述光路成像自动调节装置与所述检测装置相连，且包括光电传感器和凸透镜，所述光路成像自动调节装置适于自动调节所述光电传感器与所述凸透镜之间的距离。
  22. 根据权利要求21所述的分子检测***，其特征在于，所述光路成像自动调节装置包括：
    第三基座；
    光电传感器，所述光电传感器固定于所述第三基座上；
    调节支架，所述调节支架可移动地设在所述第三基座上，且所述调节支架上设有凸透镜，通过移动所述调节支架调节所述光电传感器与所述凸透镜之间的距离；
    第二丝杆电机，所述第二丝杆电机固定于所述第三基座上，所述第二丝杆电机中的丝杆穿过所述调节支架并带动所述调节支架移动。
  23. 根据权利要求22所述的分子检测***，其特征在于，所述调节支架与所述丝杆螺纹相连。
  24. 根据权利要求23所述的分子检测***，其特征在于，进一步包括：
    第二丝杆螺母，所述第二丝杆螺母与所述调节支架固定连接并与所述丝杆匹配相连。
  25. 根据权利要求24所述的分子检测***，其特征在于，所述调节支架的移动距离不大于30mm。
  26. 根据权利要求25所述的分子检测***，其特征在于，所述光电传感器与所述凸透镜之间的距离为30～60mm。
  27. 根据权利要求22所述的分子检测***，其特征在于，所述调节支架周壁上设有多个止抵于所述第三基座内壁的凸起。
  28. 根据权利要求23所述的分子检测***，其特征在于，所述第二丝杆电机与所述光电传感器通过CPU端智能联控。
  29. 根据权利要求23所述的分子检测***，其特征在于，所述第二丝杆电机中，丝杆为梯形丝杆、滚珠丝杆或行星滚珠丝杆，电机为直流电机、步进电机或伺服电机。
  30. 根据权利要求1～29任一项所述的分子检测***，其特征在于，所述卡槽包括：
    壳体，所述壳体的上部敞开且内部限定有容纳空间；
    定位孔，所述定位孔设在所述壳体的侧部；
    定位柱，所述定位柱的一端伸入所述定位孔；
    加热组件，所述加热组件设在所述容纳空间内；
    第二压簧，所述第二压簧设在所述容纳空间的底部，且与所述加热组件相连。
  31. 根据权利要求1所述的分子检测***，其特征在于，所述壳体的底部设有过孔，所述卡槽进一步包括固定螺钉，所述固定螺钉穿过所述过孔伸入所述容纳空间并与所述加热组件连接，所述第二压簧套设在所述固定螺钉上。
  32. 根据权利要求30所述的分子检测***，其特征在于，所述定位孔和所述定位柱均包括多个，各个所述定位孔与各个所述定位柱一一对应设置。
  33. 根据权利要求30所述的分子检测***，其特征在于，所述定位柱伸入所述定位孔的一端呈圆锥形。
  34. 根据权利要求31所述的分子检测***，其特征在于，所述加热组件包括相连的加热片和导热块，所述导热块与所述第二压簧和所述固定螺钉相连。
  35. 根据权利要求34所述的分子检测***，其特征在于，所述导热块上形成有加热室。
  36. 根据权利要求35所述的分子检测***，其特征在于，所述导热块的下部设有限位孔，所述固定螺钉伸入所述限位孔。
  37. 根据权利要求35所述的分子检测***，其特征在于，所述过孔的孔径大于所述固定螺钉的直径。
  38. 一种适用于权利要求1～37任一项所述的分子检测***的微流控试剂盒，其特征在于，所述微流控试剂盒包括：
    盒体，所述盒体内设有试剂区、样品区、反应区；
    微流控试剂盒芯片，所述微流控试剂盒芯片包括微流控管道，所述微流控管道内设有朝向液体出口的穿刺件，所述微流控试剂盒芯片通过所述微流控管道分别与所述试剂区、所述样品区和所述反应区相连。
  39. 根据权利要求38所述的微流控试剂盒，其特征在于，所述微流控管道包括：
    管道，所述管道的端部由弹性材料形成，且液体出口设在所述端部的侧壁上；
    密封膜，所述密封膜设在所述液体出口处并密封所述液体出口；
    穿刺件，具有尖端部的所述穿刺件设在与所述液体出口相对的所述端部的内壁上，所述尖端部朝向所述液体出口且在外力挤压所述端部时刺穿所述密封膜。
  40. 根据权利要求39所述的微流控试剂盒，其特征在于，所述穿刺件与所述液体出口设在所述管道的同一管径上。
  41. 根据权利要求39所述的微流控试剂盒，其特征在于，所述密封膜为锡箔纸、塑封膜或牛皮纸。
  42. 根据权利要求39所述的微流控试剂盒，其特征在于，所述密封膜的厚度区间为0.01～0.2 mm。
  43. 根据权利要求39所述的微流控试剂盒，其特征在于，所述尖端部的尖端为锥形结构，所述锥形结构为圆锥或多棱锥。
  44. 根据权利要求39所述的微流控试剂盒，其特征在于，所述尖端部由一个三角面形成，所述三角面的一边设在与所述液体出口相对的所述端部的内壁上且该边对应的顶角形成所述尖端部的尖端。
  45. 根据权利要求44所述的微流控试剂盒，其特征在于，所述三角面设在所述端部的内壁上的一边呈直线、V形、弧形或U形。
  46. 根据权利要求39所述的微流控试剂盒，其特征在于，所述穿刺件与所述管道一体成型。
  47. 根据权利要求39所述的微流控试剂盒，其特征在于，所述管道包括：
    第一板材，所述第一板材的下表面具有凹槽，所述凹槽内设有液体出口；
    弹性板材，所述弹性板材设在所述第一板材的下表面并密封所述凹槽，使得所述凹槽形成微流通道；
    其中，所述穿刺件设在所述微流通道内且与所述液体出口相对的位置上，且所述穿刺件通过弹性部件与所述第一板材的下表面相连，所述穿刺件在外力挤压所述弹性板材时刺穿所述密封膜。
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