WO2019006977A1 - 基于主动控制液体流动的多通量微流控芯片 - Google Patents

基于主动控制液体流动的多通量微流控芯片 Download PDF

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Publication number
WO2019006977A1
WO2019006977A1 PCT/CN2017/114690 CN2017114690W WO2019006977A1 WO 2019006977 A1 WO2019006977 A1 WO 2019006977A1 CN 2017114690 W CN2017114690 W CN 2017114690W WO 2019006977 A1 WO2019006977 A1 WO 2019006977A1
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Prior art keywords
liquid
flow
inlet
chamber
pool
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PCT/CN2017/114690
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English (en)
French (fr)
Inventor
许行尚
陈⋅杰佛瑞
王龙
孙威严
万其露
杨申
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南京岚煜生物科技有限公司
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Application filed by 南京岚煜生物科技有限公司 filed Critical 南京岚煜生物科技有限公司
Priority to US16/079,516 priority Critical patent/US10761092B2/en
Priority to SG11201913816TA priority patent/SG11201913816TA/en
Priority to EP17896326.0A priority patent/EP3470143B1/en
Publication of WO2019006977A1 publication Critical patent/WO2019006977A1/zh

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—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
    • 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
    • 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
    • B01L3/502738—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 integrated valves
    • 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
    • B01L3/502746—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 for controlling flow resistance, e.g. flow controllers, baffles
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00—Subject matter not provided for in other groups of this subclass
    • F16K99/0001—Microvalves
    • F16K99/0034—Operating means specially adapted for microvalves
    • F16K99/0042—Electric operating means therefor
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54393—Improving reaction conditions or stability, e.g. by coating or irradiation of surface, by reduction of non-specific binding, by promotion of specific binding
    • 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
    • B01L2200/10—Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
    • 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
    • B01L2300/069—Absorbents; Gels to retain a fluid
    • 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
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • 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
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0864—Configuration of multiple channels and/or chambers in a single devices comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
    • 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
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0867—Multiple inlets and one sample wells, e.g. mixing, dilution
    • 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
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0874—Three dimensional network
    • 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
    • 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
    • B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • 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
    • B01L2400/0633—Valves, specific forms thereof with moving parts
    • B01L2400/0655—Valves, specific forms thereof with moving parts pinch valves
    • 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
    • B01L2400/08—Regulating or influencing the flow resistance
    • B01L2400/082—Active control of flow resistance, e.g. flow controllers
    • 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
    • B01L2400/08—Regulating or influencing the flow resistance
    • B01L2400/084—Passive control of flow resistance

Definitions

  • the invention relates to a microfluidic chip based on actively controlling liquid flow, in particular to a multi-flux microfluidic chip.
  • Immunological lateral tomography diagnostic techniques are suitable as a stable and practical technique for use in a variety of real-time tests (POCT) or in the field.
  • the coefficient of variation (CV) is large due to systemic reasons, and accurate quantification cannot be achieved.
  • the immunological diagnosis method based on microfluidic technology can effectively avoid the above problems.
  • Microfluidic is divided into passive and active. Passive microfluidics still require capillary forces to achieve lateral forward chromatography of the fluid. However, due to the different viscosity of different samples, especially whole blood samples, the liquid flow rate cannot be unified.
  • Active microfluidic can effectively avoid the above problems, can give forward thrust, make the liquid flow forward evenly, and avoid the difference of test values caused by different flow rates.
  • Active microfluidic power is driven by centrifugal force, electrowetting drive, pressure drive (electrolysis pump, compressed gas pump, chemical decomposition pump, direct differential pressure drive)
  • patent 1) does not involve mixing function, and the mixing of different liquids in the chip and liquid and solids (such as embedded lyophilized reagents, etc.) is a key function of the microfluidic chip.
  • Patent 1 2) and 3) do not involve the monitoring of the exact position of the liquid as it flows through the chip.
  • the chips of the above three patents did not monitor the filling behavior of the fluid in the channel or cavity of the chip before the final test result.
  • the existing chip products have a small throughput, generally 1 to 3 projects per chip.
  • the present invention is directed to the deficiencies of the prior art, and provides a multi-flux microfluidic chip based on active control of liquid flow; it creatively distributes a liquid path evenly to multiple liquid paths, so that the detection of multiple items simultaneously becomes Possibly, greatly increasing product throughput.
  • a multi-flux microfluidic chip based on active control of liquid flow comprising a chip body, the chip body comprises an inlet chamber, a reaction-quantization chamber, a liquid path diversion chamber and a waste liquid chamber, and the inlet chamber can be connected with an external gas path Connected, the liquid path diverting cavity is arranged at a central position of the chip body; the reaction-quantitative cavity comprises two or more, distributed in a row on both sides of the liquid path diverting cavity, respectively corresponding to the first row reaction-quantitative cavity The second row reaction-quantization chamber; each reaction-quantization chamber is connected to the liquid outlet of the liquid path diverting chamber through the respective liquid path diversion branch, and the liquid inlet port of the liquid path diverting chamber can be respectively connected with the liquid inlet The liquid outlet of the chamber and the external liquid passage are connected.
  • the liquid inlet of the liquid path diverting chamber is respectively connected to the liquid inlet chamber and the external liquid passage by the inflow mechanism;
  • the inflow mechanism includes a sample inlet flow channel, a sample slow flow channel, The split flow inlet flow channel, the external liquid flow slow flow flow channel and the external liquid flow inlet flow channel; wherein: the sample inlet flow channel and the external liquid flow inlet flow channel are all ascending flow channels, and the split flow inlet flow channel
  • the flow channel of the sample inlet flow channel communicates with the liquid inlet cavity through the sample delivery flow channel, and the liquid outlet port passes through the sample slow flow channel, the split cavity inlet flow channel and the liquid channel splitting cavity in sequence.
  • the inlet port of the external liquid flow inlet passage is connected to the external liquid passage through the external liquid flow conveying passage, and the other end is connected through the external liquid flow slow flow passage, the split flow inlet flow passage and the liquid passage diverting chamber in sequence.
  • the splitter inlet flow passage is formed by inserting a plug body in the inlet member recess, the inlet member recess includes an isosceles triangular recess and a cylindrical outer sleeve;
  • the isosceles triangle inlay is inverted, and the cylindrical outer sleeve is arranged along the midline of the isosceles triangle inlay, starting from the bottom edge of the isosceles triangle insert, and extending the apex portion of the isosceles triangle insert to form the split cavity a circular outflow channel of the inflow channel;
  • the plug body has a cylindrical plug matching the cylindrical outer sleeve, and two inclined outer wall faces are symmetrically arranged with the center line of the cylindrical plug, respectively embedded with the isosceles triangle Two isosceles oblique sides of the groove
  • the inclined liquid inlet channel is connected to the sample slow flow channel, and the other inclined liquid inlet channel is connected to the external liquid flow slow flow channel.
  • the liquid path diverting chamber has a sample inlet port, an external liquid inlet port and a plurality of liquid outlets, and the sample inlet port of the liquid path diverting chamber communicates with the inlet chamber through the sample delivery channel, the liquid
  • the external liquid inlet of the road diversion chamber communicates with the external liquid passage through the external liquid flow conveying passage;
  • the liquid outlet of the liquid passage diverting chamber communicates with the reaction-quantization chamber through the respective liquid path diverting branch; and each liquid path
  • the split branch is symmetrically distributed on both sides of the liquid inlet port sample inlet port and the external liquid flow inlet port; the channel width of each liquid channel branch branch is inversely proportional to the channel length.
  • the reaction-quantization chamber comprises a labeled antibody placement chamber and a coating antibody placement chamber; the coating antibody placement chamber is disposed at a middle position of the reaction-quantization chamber, and the coated antibody is placed
  • the chamber has a reaction tank inlet branch and a reaction tank outlet branch; the reaction-quantization chamber is provided with a labeled antibody placement chamber on both sides of the reaction pool inlet branch and the reaction cell outlet branch line.
  • a valve device is installed on each of the reaction-quantization chamber and the corresponding waste liquid chamber, and the valve device includes:
  • a detecting mechanism for sensing whether a fluid flows through a mounting position of the valve device
  • the value fed back by the detecting mechanism indicates that the fluid can automatically close when the fluid flows through the valve device installation position, and is in a closed state;
  • the valve device in the closed state can be opened periodically and is in a circulating state
  • the fluid can be circulated in the valve device under the impeding air flow provided by the air passage;
  • the sealing member is a conductive sealing ring, comprising an outer sealing ring, an inner sealing film and a probe contact; the inner sealing film is in an inner ring of the outer sealing ring; the probe contact is connected with the outer sealing ring;
  • the pressing mechanism includes a lower pressing head, and the lower pressing head is located above the inner sealing film;
  • the detecting mechanism comprises a detecting probe connected in linkage with the lower pressing head and located above the probe contact, and the spacing between the detecting probe and the probe contact is smaller than the spacing between the lower pressing head and the inner sealing film ;
  • microfluidic flow passage at the installation position of the valve device is divided into a micro valve inlet section and a microvalve outlet section by a microfluidic flow passage;
  • the micro valve inlet section has a liquid outlet, and the microvalve outlet section has a liquid inlet;
  • the inner sealing membrane can cover the liquid outlet of the micro valve inlet section and the liquid inlet of the micro valve outlet section, and is sealed by the outer sealing ring;
  • the pressing mechanism When the lower pressing head of the pressing mechanism is facing down with the detecting probe facing the conductive sealing ring, when the detecting probe touches the probe contact, the pressing mechanism stops downward, and at this time, there is a gap between the lower pressing head and the inner sealing film;
  • the pressing mechanism When the data sensed by the detecting probe changes, indicating that the fluid flows through the microfluidic flow path at the installation position of the valve device, the pressing mechanism is triggered to push the lower pressing head to continue downward until the lower pressing head presses the inner sealing film.
  • the valve device In order to simultaneously seal the liquid outlet of the micro valve inlet section and the inlet port of the microvalve outlet section, the valve device is in a closed state;
  • the valve device When there is a gap between the lower pressing head of the pressing mechanism and the inner sealing membrane, the valve device is in an open state, and the internal sealing membrane has a deformation characteristic, ensuring that fluid can flow out from the liquid outlet of the micro valve inlet section, from the microvalve The liquid inlet of the liquid discharge section flows in.
  • the waste liquid chamber body is arranged in three parts, arranged in a semi-enclosed shape on the periphery of the chip body, including a first waste liquid chamber on both sides of the chip body, a second waste liquid chamber, and the first a third waste liquid chamber connected to the waste liquid chamber and the second waste liquid chamber; wherein: the first waste liquid chamber can communicate with the first row reaction-quantization chamber, and the second waste liquid chamber can react with the second row reaction-quantitative The cavity is connected.
  • the first waste liquid chamber and the second waste liquid chamber have the same structure, including a waste liquid pool a, a middle cover plate a covering the waste liquid pool a, and a cover on the middle cover plate a.
  • the upper cover a; the middle cover a has a water-absorbent paper recess a for accommodating the absorbent paper on the surface facing the waste liquid pool a, and a plurality of spaced-apart conductive seal groove at the surface facing the upper cover a a conductive sealing ring is disposed in the conductive sealing ring inserting groove, and the upper layer cover a is disposed at a position corresponding to each of the conductive sealing ring cavities with a capacitor probe passing hole and a pressing mechanism lower pressing head passing hole;
  • the inner wall surface of the liquid pool a is spaced apart from the plurality of toothed flow guiding members, and the absorbent paper positioning column is disposed at a position close to the tip end of the toothed flow guiding member; the inner side wall surface
  • the third waste liquid chamber includes a waste liquid pool b, a middle cover plate b covering the open end of the waste liquid pool b, and an upper cover plate b covering the middle cover plate b; the middle layer
  • the cover b is provided with an absorbent paper mounting groove b on the surface facing the upper cover b, and the bottom of the absorbent paper mounting groove b is provided with an air outlet a, and the upper cover b is at the notch with the absorbent paper mounting groove b.
  • the air holes b are formed through the opposite plates.
  • Another technical object of the present invention is to provide a multi-flux microfluidic chip based on actively controlling liquid flow, comprising a chip body having a three-piece structure including upper layers and middle layers arranged in order from top to bottom. a chip and a lower layer chip; the lower layer chip is provided with a whole blood filter pool, a reaction-quantitative pool, and a waste liquid pool; the middle layer chip is provided with a sample injection tank at a position corresponding to the whole blood filter pool, and the reaction-quantitative pool The middle layer reaction cell through hole is disposed at the corresponding position, and the middle cover plate covering the open end of the waste liquid pool is disposed at a position corresponding to the waste liquid pool; the upper layer chip is provided with the outer circumference of the injection groove at a position corresponding to the injection tank.
  • the upper reaction cell through hole is disposed at a position corresponding to the through hole of the middle reaction cell, and the upper cover plate is disposed at a position corresponding to the middle cover plate;
  • the waste liquid pool is divided into three parts and arranged in a semi-enclosed shape on the chip
  • the periphery of the body includes a first waste liquid pool on both sides of the chip body, a second waste liquid pool, and a third waste liquid pool connecting the first waste liquid pool and the second waste liquid pool;
  • the liquid layer diverting pool is further disposed on the lower layer chip, the liquid path diverting pool is disposed at an intermediate position of the lower layer chip, and a sample conveying branch is disposed between one end of the liquid path diverting pool and the whole blood filter pool, and the other end is connected with the external liquid
  • An external liquid flow conveying branch is arranged between the roads;
  • the liquid path diverting pool is selectively connected to the sample conveying branch and the external liquid flow conveying branch through the inflow mechanism;
  • the inlet mechanism includes a sample inlet flow channel, a sample slow flow channel, a split cavity inlet flow channel, an external liquid flow slow flow channel, and an external liquid flow inlet flow channel; wherein: the sample inlet flow channel and the external liquid flow
  • the inlet flow channel is an ascending flow channel, and the inflow channel of the diversion chamber is a descending flow channel; the inlet port of the sample inlet channel is connected to the inlet chamber through the sample delivery branch, and the liquid outlet is sequentially passed through the sample.
  • the flow channel and the diversion chamber inflow channel are in communication with the liquid channel diversion chamber; the inlet port of the external liquid flow inlet channel is connected to the external liquid channel through the external liquid flow delivery branch, and the other end is sequentially passed through the external liquid flow.
  • the flow channel and the diversion chamber inflow channel are in communication with the liquid channel diversion chamber.
  • the splitter inlet flow passage is formed by inserting a plug body in the inlet member recess, the inlet member recess includes an isosceles triangle insert and a cylindrical outer sleeve, the isosceles triangular insert is inverted, the cylinder
  • the outer sleeve is arranged along the midline of the isosceles triangle inset, starting from the bottom edge of the isosceles triangle insert and elongating the apex portion of the isosceles triangle insert to form a circular outflow of the inflow lumen of the split chamber
  • the plug body has a cylindrical plug matched with the cylindrical outer sleeve, and two inclined outer wall faces are symmetrically arranged with the center line of the cylindrical plug, respectively forming a slope with the isosceles oblique sides of the isosceles triangle insert groove
  • one of the inclined inlet flow channels is in communication with the sample slow flow channel
  • the other inclined inlet flow channel is in communication with the external liquid flow
  • the liquid path diverting pool is symmetrically arranged with five liquid path diverting branches on both sides of the sample conveying branch line and the external liquid flow conveying branch line, and each liquid path diverting branch is connected with a reaction-quantitative pool.
  • each liquid path A backflow prevention device is disposed between the split branch circuit and the respective reaction-quantitative cells; in addition, the reaction-quantity pools on both sides of the liquid channel splitter pool are arranged in a row, corresponding to the first row reaction-quantitative a second row reaction-quantity cell; the first waste liquid pool is connectable with the first row reaction-quantitative tank; the second waste liquid pool is connectable with the second row reaction-quantitative tank;
  • the first waste liquid pool and the second waste liquid pool have the same structure;
  • the middle cover of the first waste liquid pool has the absorbent paper insert groove a for accommodating the absorbent paper on the surface facing the first waste liquid pool, and faces the first waste
  • the plate surface of the upper cover of the liquid pool has a plurality of spaced-apart conductive sealing ring inserts, and the conductive sealing ring is fitted with a conductive sealing ring, and the upper cover of the first waste liquid pool is embedded with each conductive sealing ring
  • Corresponding positions are arranged with a capacitor probe through hole and a lower pressing mechanism lower pressing head through hole;
  • the middle cover of the third waste liquid pool is provided with an absorbent paper installation groove b on the surface facing the upper cover, and the bottom of the suction paper installation groove b is provided with an air outlet a, and the upper layer of the third waste liquid pool
  • the cover plate has a vent hole b formed through a plate surface opposed to the notch of the absorbent paper mounting groove b.
  • the present invention has the following advantages over the prior art:
  • the invention creatively distributes a liquid path evenly to ten liquid paths, and simultaneously performs detection of 10 items, thereby greatly improving product throughput.
  • the invention adopts the valve device and anti-backflow device which are creatively designed by the company, and combines the gas path as the driving force of the liquid forward, can control the liquid velocity in the flow channel at will, and can be fixed in a certain area for the incubation reaction. . Achieve true microfluidic purposes.
  • the present invention can achieve quantitative loading in this sense by means of a quantification tank.
  • FIG. 1 is a schematic structural view of a microfluidic chip based on actively controlling liquid flow according to the present invention
  • Figure 1 1, the upper chip; 2, the middle chip; 3, the lower chip; 4, the pneumatic device; 5-1, the pressing mechanism; 5-2, the capacitance probe; 5-3, the conductive sealing ring; Liquid path device; 7-1, third absorbent paper; 7-2, second absorbent paper; 7-3, first absorbent paper; 8, blood filter paper;
  • FIG. 2 is a top plan view of the microfluidic chip of the present invention.
  • FIG. 2 5, valve device; 9-3, pneumatic interface; 9-2, sample hole; 9-1, venting hole; 10, off-chip positioning part; 11, reaction-quantitative cavity; ; 13, liquid circuit interface; 14, capacitor probe Detection port;
  • FIG. 3 is a schematic structural view of a lower layer chip according to the present invention.
  • Figure 4a is an enlarged schematic view of a portion A of Figure 3;
  • Figure 4b is a plan view of portion A of Figure 3;
  • FIG. 3 4a, 4b: 3-1, reaction-quantitative pool; 3-2, whole blood filter tank; 3-2-1, side tank wall of whole blood filter tank; 3-3, second waste liquid Pool; 3-3-1, zigzag flow guide on the inner side wall of the second waste liquid pool; 3-4, first waste liquid pool; 3-4-1, absorbent paper fixing member of the first waste liquid pool 3-4-2, a serrated flow guide on the inner side wall of the first waste liquid pool; 3-5, a third waste liquid pool; 3-6, a chip fixing column; 3-7, a liquid path diverting pool;
  • Figure 5 is a schematic enlarged plan view of the liquid path diverting pool of the present invention.
  • Fig. 5 liquid channel diverting pool
  • 3-7-1 sample conveying flow channel
  • 3-7-2 to 3-7-11 10 parallel liquid channel diversion branches of the diversion pool
  • 7-12 external liquid flow (cleaning liquid and color developing liquid) conveying flow channel
  • Figure 6 is a schematic enlarged view of the quantitative-reaction cell
  • FIG. 6 3-1-1, coated antibody placement pool; 3-1-2, labeled antibody placement pool; 3-1-3, reaction cell inlet branch; 3-1-4, reaction cell Outlet branch;
  • FIG. 7 is a schematic structural view of a middle chip
  • Figure 8 is a schematic view showing the structure of the liquid inlet portion of the liquid path diverting pool
  • FIG. 7-8 2-1, injection tank; 2-2, conductive sealing ring embedding; 2-3, anti-reflux outlet; 2-4, liquid inlet part of the liquid diverting pool; 2-4 -1, sample inlet flow channel; 2-4-2, sample slow flow channel; 2-4-3, split cavity inlet flow channel; 2-4-4, external liquid flow slow flow channel; 4-5, external liquid flow inlet flow channel; 2-5, absorbent paper installation groove; 2-5-1, waste liquid pool in the middle layer chip outlet hole; 2-6, quantitative-reaction cell through hole; 2 -7, the chip fixed column hole;
  • Figure 9a is a top view of the upper chip
  • Figure 9b is a bottom view of the upper chip
  • Figure 9c is a schematic structural view of a liquid inlet member of the liquid path diverting pool
  • Figure 9a, Figure 9b, Figure 9c 1-1, injection groove outer ring; 1-2, capacitance probe through hole; 1-3, quantitative-reaction cell cover; 1-4, lower pressure mechanism through hole; 1-5, the vent hole of the waste liquid pool in the upper layer chip; 1-6, the liquid inlet part of the liquid path splitting pool;
  • Figure 10a is a schematic view showing the structure of the left waste liquid chamber in one direction
  • Figure 10b is a schematic view showing the structure of the left side waste liquid chamber in another direction
  • Figure 10a, Figure 10b 1-2, capacitance probe through hole; 2-2, conductive seal ring groove; 2-2-1, left side waste liquid pool in the water-absorbing paper groove; 3-4, left side waste Liquid pool
  • Figure 11a is a schematic view showing the structure of the right waste liquid chamber of the present invention.
  • Figure 11b is a partially enlarged schematic view of the right waste liquid chamber
  • Figure 11c is a schematic view showing the structure of the right side of the waste liquid chamber
  • Figure 12 is a schematic view showing the structure of the front side waste liquid chamber.
  • spatially relative terms such as “above”, “above”, “on top”, “above”, etc., may be used herein to describe as in the drawings.
  • the exemplary term “above” can include both “over” and "under”.
  • the device can also be positioned in other different ways (rotated 90 degrees or in other orientations).
  • the invention discloses a multi-flux microfluidic chip based on actively controlling liquid flow, comprising a chip body, wherein the chip body comprises an inlet cavity, a reaction-quantization cavity, a liquid channel diversion cavity and a waste liquid cavity, and the liquid inlet cavity can It is connected with the external gas path, and the liquid channel diverting cavity can be respectively connected with the reaction-quantization cavity and the external liquid path, wherein:
  • the liquid path diverting cavity is arranged at a middle position of the chip body, and has a sample inlet port, an external liquid inlet port and a plurality of liquid outlets, and the sample inlet port of the liquid channel diverting cavity passes through the sample conveying channel and the inlet
  • the liquid chamber is connected, and the external liquid inlet port of the liquid path diverting chamber is connected to the external liquid path through the external liquid flow conveying channel; the liquid outlet port of the liquid path diverting chamber is connected to the reaction-quantization chamber through the respective liquid path diverting branch
  • each liquid channel branching branch is symmetrically distributed on both sides of the liquid channel splitting chamber sample inlet port and the external liquid stream inlet port; the channel width of each liquid channel branching branch is inversely proportional to the channel length.
  • the liquid inlet of the liquid channel splitting chamber is respectively connected with the liquid inlet chamber and the external liquid passage through the inlet mechanism;
  • the inlet mechanism includes a sample inlet flow channel, a sample slow flow channel, a split cavity inlet flow channel, The external liquid flow slow flow channel and the external liquid flow inlet flow channel; wherein: the sample inlet flow channel and the external liquid flow inlet flow channel are all ascending flow channels, and the split flow inlet flow channel is a descending flow channel;
  • the inlet port of the inlet flow channel communicates with the inlet chamber through the sample delivery channel, and the outlet port sequentially communicates with the liquid channel diversion chamber through the sample slow flow channel and the split chamber inlet flow channel; the external liquid flow enters the liquid flow
  • the inlet port of the channel communicates with the external liquid path through the external liquid flow conveying channel, and the other end is connected to the liquid channel diverting cavity through the external liquid flow slow flow channel and the split flow channel.
  • the splitter inlet flow passage is formed by inserting a plug body in the liquid inlet part recess, the liquid inlet part inserting groove includes an isosceles triangle insert groove and a cylindrical outer sleeve; the isosceles triangle insert groove is inverted
  • the cylindrical outer sleeve is arranged along the midline of the isosceles triangular inlay, starting from the bottom edge of the isosceles triangular recess and projecting the apex of the isosceles triangular recess to form a circular shape of the inflow passage of the diversion chamber a flow passage;
  • the plug body has a cylindrical plug matched with the cylindrical outer sleeve, and two inclined outer wall faces are symmetrically arranged with the center line of the cylindrical plug, respectively, and the isosceles oblique sides of the isosceles triangular recessed groove
  • a slanted liquid inlet passage is formed, wherein one inclined inlet flow passage is in communication with the
  • the reaction-quantization chamber comprises two or more, and there are ten in the drawing, which are distributed in two rows on both sides of the liquid channel splitting cavity, respectively corresponding to the first row reaction-quantization cavity and the second row reaction-quantization cavity; Each of the reaction-quantization chambers is in communication with the liquid outlet of the liquid path splitting chamber through a respective liquid path branching branch.
  • the reaction-quantization chamber of the present invention comprises a labeling antibody placement chamber and a coating antibody placement chamber; the coating antibody placement chamber is disposed at a middle position of the reaction-quantization chamber, and the coating antibody placement chamber has a reaction chamber.
  • Liquid branch, reaction cell outlet branch; reaction-quantitation chamber is provided with a standard on both sides of the reaction pool inlet branch and the reaction tank outlet branch connection Record the antibody placement cavity.
  • the waste liquid chamber is divided into three parts and arranged in a semi-enclosed shape on the periphery of the chip body, including a first waste liquid chamber on both sides of the chip body, a second waste liquid chamber, and a first waste liquid chamber and a second waste. a third waste liquid chamber connected to the liquid chamber; wherein: the first waste liquid chamber is connectable with the first row reaction-quantization chamber, and the second waste liquid chamber is connectable with the second row reaction-quantization chamber.
  • the first waste liquid chamber and the second waste liquid chamber have the same structure, including a waste liquid pool a, a middle cover plate a covering the waste liquid pool a, and an upper cover plate a covering the middle cover plate a; the middle layer
  • the cover plate a has a water-absorbent paper groove a for accommodating the absorbent paper on the surface facing the waste liquid pool a, and a plurality of spaced-apart conductive seal groove grooves on the surface facing the upper cover plate a, and the conductive seal ring is embedded in the groove
  • a conductive sealing ring is installed, and the upper cover plate a is disposed at a position corresponding to each of the conductive sealing ring cavities with a capacitor probe passing hole and a lower pressing mechanism lower pressing head passing hole;
  • the inner wall surface of the waste liquid pool a is spaced apart a plurality of toothed flow guiding members are disposed, and an absorbent paper positioning column is disposed at a position close to the tip end of the toothed flow guiding member;
  • the third waste liquid chamber comprises a waste liquid pool b, a middle cover plate b covering the open end of the waste liquid pool b, and an upper cover plate b covering the middle cover plate b; the middle cover plate b facing the upper cover
  • the suction plate mounting groove b is provided on the plate surface of the plate b, and the air outlet hole a is opened in the groove bottom of the absorbent paper mounting groove b, and the upper cover plate b is opened through the plate surface opposite to the notch of the absorbent paper mounting groove b. Vent vent b.
  • a valve device is installed on each of the reaction-quantization chambers and the corresponding waste liquid chamber.
  • the valve device used in the present invention can be more specifically described in Chinese Patent No. 2017102131082, which includes:
  • a detecting mechanism for sensing whether a fluid flows through a mounting position of the valve device
  • the value fed back by the detecting mechanism indicates that the fluid can automatically close when the fluid flows through the valve device installation position, and is in a closed state;
  • the valve device in the closed state can be opened periodically and is in a circulating state
  • the fluid can be circulated in the valve device under the impeding air flow provided by the air passage;
  • the sealing member is a conductive sealing ring, comprising an outer sealing ring, an inner sealing film and a probe contact; the inner sealing film is in an inner ring of the outer sealing ring; the probe contact is connected with the outer sealing ring;
  • the pressing mechanism includes a lower pressing head, and the lower pressing head is located above the inner sealing film;
  • the detecting mechanism comprises a detecting probe connected in linkage with the lower pressing head and located above the probe contact, and the spacing between the detecting probe and the probe contact is smaller than the spacing between the lower pressing head and the inner sealing film ;
  • microfluidic flow passage at the installation position of the valve device is divided into a micro valve inlet section and a microvalve outlet section by a microfluidic flow passage;
  • the micro valve inlet section has a liquid outlet, and the microvalve outlet section has a liquid inlet;
  • the inner sealing membrane can cover the liquid outlet of the micro valve inlet section and the liquid inlet of the micro valve outlet section, and is sealed by the outer sealing ring;
  • the pressing mechanism When the lower pressing head of the pressing mechanism is facing down with the detecting probe facing the conductive sealing ring, when the detecting probe touches the probe contact, the pressing mechanism stops downward, and at this time, there is a gap between the lower pressing head and the inner sealing film;
  • the pressing mechanism When the data sensed by the detecting probe changes, indicating that the fluid flows through the microfluidic flow path at the installation position of the valve device, the pressing mechanism is triggered to push the lower pressing head to continue downward until the lower pressing head presses the inner sealing film.
  • the valve device In order to simultaneously seal the liquid outlet of the micro valve inlet section and the inlet port of the microvalve outlet section, the valve device is in a closed state;
  • the valve device When there is a gap between the lower pressing head of the pressing mechanism and the inner sealing membrane, the valve device is in an open state, and the internal sealing membrane has a deformation characteristic, ensuring that fluid can flow out from the liquid outlet of the micro valve inlet section, from the microvalve The liquid inlet of the liquid discharge section flows in.
  • the anti-reflux device is installed on the liquid-path branching branch between each reaction-quantization chamber and the liquid-path splitting chamber of the present invention.
  • the backflow prevention device used in the present invention please refer to Chinese Patent No. 2017102133849, including : microfluidic flow channel and anti-reflux structure, the anti-reflux structure is located above the microfluidic flow channel, and has a backflow prevention channel; the anti-reflux flow channel can raise the liquid level of the microfluidic flow channel at the installation position of the anti-reflux structure
  • the microfluidic flow channel is connected to the gas path, under the pressure provided by the gas path, the pressure of the liquid level of the microfluidic flow channel raised by the backflow prevention channel is overcome, and the sides of the backflow prevention device are promoted.
  • the fluid in the microfluidic flow channel is in a flow state.
  • the extending direction of the anti-reflux flow passage is perpendicular to the extending direction of the microfluidic flow passage at the installation position of the anti-reflux structure; and the microfluidic flow passage at the installation position of the anti-reflux structure is divided into two by the microfluidic flow passage spacer
  • the segments are respectively a microfluidic inlet flow channel and a microfluidic fluid outlet flow channel; the upper end of the anti-reflux flow channel is closed, and the lower end is bridged over the microfluidic flow channel spacer, and respectively is connected with the microfluidic flow inlet The flow channel and the microfluidic fluid outlet are connected.
  • the anti-return flow channel has anti-reflux bumps, and an anti-reflux bump and a backflow prevention flow path are formed between Two anti-reflux connecting flow channels; the two anti-reflux connecting flow channels are respectively connected with the microfluidic inlet flow channel and the microfluidic flow channel; the lower end of the anti-reflux bump and the backflow prevention channel The lower end is flush, and the upper end of the anti-reflux bump is lower than the upper end of the anti-backflow runner.
  • the anti-reflux bump is disposed in a trapezoidal shape in a cross section between the two backflow prevention communication passages.
  • the microfluidic channel spacer is a wedge block
  • the backflow prevention channel is a wedge groove having a shape similar to that of the microfluidic channel spacer.
  • the microfluidic flow channel at the installation position of the anti-reflux structure is symmetrically arranged on both sides of the microfluidic flow channel spacer with a wedge-shaped connecting column, and the anti-return flow channel has a wedge-shaped connecting groove that is coupled with the wedge-shaped connecting column.
  • the liquid inlet cavity of the present invention can be referred to the Chinese patent application 2017103771423, including a whole blood filter sample cell and a top cover covering the whole blood filter sample cell, and the injection site is disposed on the top cover; the whole blood filter sample cell Having a filter sample outlet, the side wall of the whole blood filter sample cell is extended in a tapered manner to the outlet of the filter sample, the side wall extending in a tapered manner is arranged in a tooth shape with drainage; in the whole blood filter sample pool Whole blood filter paper is placed, and the sides of the whole blood filter paper can be in contact with the convex tips of the teeth of the toothed side walls of the adjacent whole blood filter sample cells.
  • the injection portion has an annular groove and an annular flange, the outer side wall of the annular flange is an inner side wall of the annular groove, and the air source interface is disposed in the annular groove;
  • the venting hole comprises a first venting hole and a second venting hole;
  • the first venting hole is disposed at an end surface of the annular flange, the annular flange is engaged with the sampling hole through a converging transition surface, the second venting hole is disposed on the converging transition surface of the annular plenum against the inner wall of the annular flange, and the second venting hole The position is adjacent to the position of the first venting hole.
  • a multi-flux microfluidic chip based on active control of liquid flow includes a chip body having a three-piece structure including an upper layer chip and a middle layer chip arranged in order from top to bottom. And the underlying chip; where:
  • the lower layer chip is provided with a whole blood filter pool, a reaction-quantification pool, a waste liquid pool, and a liquid path diverting pool, wherein:
  • the waste liquid pool is divided into three parts and arranged in a semi-enclosed shape on the periphery of the chip body, including a first waste liquid pool on the two sides of the chip body, a second waste liquid pool, and a first waste liquid pool and a second waste liquid. a third waste liquid pool connected to the liquid pool;
  • the liquid path diverting pool is disposed at an intermediate position of the lower layer chip, and a sample conveying flow path is disposed between one end of the liquid path diverting pool and the whole blood filter pool, and an external liquid flow conveying flow path is disposed between the other end and the external liquid path.
  • a sample conveying flow path is disposed between one end of the liquid path diverting pool and the whole blood filter pool, and an external liquid flow conveying flow path is disposed between the other end and the external liquid path.
  • the liquid channel diverting pool as shown in Fig. 5, is provided with 10 liquid-path diverting branches, and five liquid-path diverting branches are symmetrically arranged on both sides of the sample conveying flow channel and the external liquid flow conveying channel connecting line.
  • the road, each liquid branch branch branch is connected with a reaction-quantification pool, and a backflow prevention device is arranged between each liquid channel branch branch and the respective connected reaction-quantification pool;
  • the reaction-quantification pool includes a labeled antibody placement pool and a coating antibody placement pool; the coating antibody placement pool is disposed at a middle position of the reaction-quantification pool, and the coating antibody placement pool has The reaction tank inlet branch and the reaction tank outlet branch; the reaction-quantification tank is provided with a labeled antibody placement tank on both sides of the reaction tank inlet branch and the reaction tank outlet branch connection.
  • the liquid path diverting pool is selectively connected to the sample delivery branch and the external liquid flow delivery branch through the inflow mechanism.
  • the middle layer chip as shown in FIG. 7, is provided with a sampling tank at a position corresponding to the whole blood filter pool, and a middle layer reaction tank through hole is provided at a position corresponding to the reaction-quantification pool, corresponding to the waste liquid pool A middle cover covering the open end of the waste pool is provided at the location.
  • the inflow mechanism includes a sample inlet flow path, a sample slow flow flow path, a split flow inlet flow path, an external liquid flow slow flow flow path, and an external liquid flow inlet flow path; wherein: the sample enters The liquid flow channel and the external liquid flow inlet flow channel are all ascending flow channels, and the diversion chamber inflow flow channel is a descending flow channel; the liquid inlet of the sample inlet flow channel communicates with the inlet liquid chamber through the sample delivery branch
  • the liquid port is sequentially connected to the liquid flow diverting flow passage through the sample slow flow flow passage and the split flow inlet flow passage; the liquid inlet of the external liquid flow inlet flow passage is connected to the external liquid passage through the external liquid flow transport branch, and the other end is connected Then, through the external liquid flow slow flow channel, the split flow inlet flow channel and the liquid path split flow chamber are connected in sequence.
  • the splitter inlet flow passage is formed by inserting a plug body in the inlet member recess, the inlet member recess includes an isosceles triangle insert and a cylindrical outer sleeve, the isosceles triangular insert is inverted, the cylinder
  • the outer sleeve is arranged along the midline of the isosceles triangle inset, starting from the bottom edge of the isosceles triangle insert and elongating the apex portion of the isosceles triangle insert to form a circular outflow of the inflow lumen of the split chamber
  • the plug body has a cylindrical plug matched with the cylindrical outer sleeve, and two inclined outer wall faces are symmetrically arranged with the center line of the cylindrical plug, respectively forming a slope with the isosceles oblique sides of the isosceles triangle insert groove
  • one of the inclined inlet flow channels is in communication with the sample slow flow channel
  • the other inclined inlet flow channel is in communication with the external liquid flow
  • the upper chip is provided with an outer ring of the injection slot at a position corresponding to the injection slot, and an upper reaction cell through hole is disposed at a position corresponding to the through hole of the middle reaction cell, and the middle cover is Board corresponding bit Set the upper cover.
  • the first waste liquid pool and the second waste liquid pool have the same structure; the middle cover of the first waste liquid pool has water absorption on the surface facing the first waste liquid pool.
  • the paper absorbent paper is embedded in the groove a, and the surface of the upper cover plate facing the first waste liquid pool has a plurality of spaced-apart conductive sealing ring inserts, and the conductive sealing ring is fitted with a conductive sealing ring, and the first waste
  • the upper cover plate of the liquid pool is arranged with a capacitor probe through hole and a lower pressing mechanism lower pressing head through hole at a position corresponding to each conductive sealing ring slot;
  • the middle cover of the third waste liquid pool is provided with an absorbent paper mounting groove b on the surface facing the upper cover, and the bottom of the suction paper mounting groove b is provided with an air outlet a, and The upper cover of the three waste liquid pool is provided with a vent b through the plate surface opposite to the notch of the absorbent paper mounting groove b.
  • the width of the channel is inversely proportional to the length of the channel, which helps to balance the resistance of the liquid flow.
  • the liquid flows downward from directly above the middle circle and is evenly distributed to 10 flow paths.
  • D. 10 flow path ends plus a resistance device for liquid movement (backflow prevention) to further eliminate the difference of each flow channel.
  • coated antibody and the labeled antibody are physically segmented, effectively removing non-specific binding and improving the signal to noise ratio.
  • the chip design is simple and convenient.
  • the serrated deflector prevents liquid from flowing out of the gas passage.
  • Waste chip pool mid-chip segment - increase the volume of the waste pool.
  • the middle chip and the upper chip are provided with air holes to further eliminate possible liquid leakage and bubble leakage.
  • the present invention has the following advantages:
  • the invention designs a liquid channel uniform flow dividing device to improve the flux of the product
  • the invention creatively designs the valve device, the backflow prevention device, and the gas path as the forward driving force of the liquid, can control the liquid velocity in the flow channel at will, and can be fixed in a certain region to perform the incubation reaction. Achieve true microfluidic purposes
  • the invention adds a water absorbing material in the waste liquid pool to prevent the external liquid splashing, and at the same time, the gas passage, the serrated flow guiding device, the middle layer chip absorbent paper and the like are skillfully designed to effectively avoid liquid leakage. Make the production process simple and practical.
  • the invention adopts a sealing ring made of conductive rubber, together with the device capacitance detecting probe, to detect the liquid flow state.
  • the invention combines the quantitative tank, the marker tank and the reaction tank into one, which can effectively quantitatively add the sample, and at the same time can place the labeled antibody and the coated antibody in different regions in the same tank, thereby effectively avoiding non-specific binding and improving Signal to noise ratio, while the design is simple and practical.
  • the invention connects the chip through the liquid path, cleans the reaction tank, effectively reduces the reaction background and improves the sensitivity of the product.

Abstract

基于主动控制液体流动的多通量微流控芯片，包括芯片本体，芯片本体包括进液腔、反应-定量腔（11）、液路分流腔以及废液腔，进液腔能够与外接气路连通，液路分流腔布置在芯片本体的中部位置处；反应-定量腔（11）包括两个以上，呈排状分布在液路分流腔的两侧，分别对应为第一排状反应-定量腔、第二排状反应-定量腔；各反应-定量腔均通过各自的液路分流支路与液路分流腔的出液口连通，液路分流腔的进液口则能够分别与进液腔的出液口以及外接液路连通。

Description

基于主动控制液体流动的多通量微流控芯片 技术领域
本发明涉及一种基于主动控制液体流动的微流控芯片，尤其是一种多通量微流控芯片。
背景技术
免疫侧向层析诊断技术作为一种稳定和实用的技术适合在多样的即时检验(POCT)或者现场使用。
在免疫层系反应系统中，由于系统原因导致变异系数CV(Coefficient of Variation)大，无法达到精确定量。而基于微流控技术的免疫诊断方法，可以有效的避免上述问题。
微流控又分被动式和主动式两种。被动式微流控还是需要毛细血管力来达到液体向前的侧向层析。但是由于不同样本特别是全血样本的粘稠度不同，导致液体流速无法统一。
主动式微流控可以有效避免上述问题，可以给向前的推力，使液体均匀的向前流动，避免因为不同流速导致的测试值差异。
主动式微流控的动力有离心力驱动、电润湿驱动、压力驱动(电解泵、压缩气体泵、化学分解泵、直接气压差驱动)
但是如果要达到随意控制液体速度的目的，不但要有推动力，还要有阀门控制，还要有防回流免得液体，因为压力去除，回流回去。
现有相关技术，芯片的制作以及芯片的应用，请参考以下专利：
1)CN203899622U一种微流控芯片
2)CN106353491A微流控床旁边快速诊断试剂盒
3)CN205941345U用于生物检测的微流控芯片
其中，专利1)中，未涉及混合功能，而芯片中不同液体以及液体与固体(比如预埋的冻干试剂等)的混合是微流控芯片的一个关键功能。
专利2)和3)中，未对加入到芯片中的样本液体进行定量，而要实现定量检测，必须实现对加入的样本的定量和预先放置于芯片内的试剂的定量。
专利1)，2)和3)中都未涉及液体在芯片中流动时准确位置的监测，换句 话说，上述3项专利的芯片在最后的检测结果之前没有对流体在芯片内通道或腔体的填充行为做监测。
另外，现有的芯片产品通量不大，一般就1到3个项目每芯片。
发明内容
本发明针对现有技术的不足，提供一种基于主动控制液体流动的多通量微流控芯片；其创造性地将一道液路均匀分布到多道液路，使得多个项目的检测同时进行成为可能，大大提高产品通量。
为实现上述的技术目的，本发明将采取如下的技术方案：
一种基于主动控制液体流动的多通量微流控芯片，包括芯片本体，该芯片本体包括进液腔、反应-定量腔、液路分流腔以及废液腔，进液腔能够与外接气路连通，所述液路分流腔布置在芯片本体的中部位置处；反应-定量腔包括两个以上，呈排状分布在液路分流腔的两侧，分别对应为第一排状反应-定量腔、第二排状反应-定量腔；各反应-定量腔均通过各自的液路分流支路与液路分流腔的出液口连通，而液路分流腔的进液口则能够分别与进液腔的出液口以及外接液路连通。
作为本发明的进一步改进，所述液路分流腔的进液口通过进流机构分别与进液腔、外接液路择一连通；进流机构包括样品进液流道、样品缓流流道、分流腔进流流道、外接液流缓流流道以及外接液流进液流道；其中：样品进液流道、外接液流进液流道均为上升流道，分流腔进流流道则为下降流道；样品进液流道的进液口通过样品输送流道与进液腔连通，出液口则依次通过样品缓流流道、分流腔进流流道与液路分流腔连通；外接液流进液流道的进液口通过外接液流输送流道与外接液路连通，另一端则依次通过外接液流缓流流道、分流腔进流流道与液路分流腔连通。
作为本发明的进一步改进，所述分流腔进流流道通过在进液部件嵌槽中嵌装塞体而形成，所述进液部件嵌槽包括等腰三角形嵌槽以及圆柱形外套管；所述等腰三角形嵌槽倒置，圆柱形外套管沿着等腰三角形嵌槽中线位置布置，起始于等腰三角形嵌槽的底边，并外延出等腰三角形嵌槽的顶点部位，形成分流腔进流流道的圆形出流道；塞体具有与圆柱形外套管匹配的圆柱形堵头，并以圆柱形堵头的中心线对称地设置两个倾斜外壁面，分别与等腰三角形嵌槽的两等腰斜边形成 倾斜进液流道，其中一条倾斜进液流道与样品缓流流道连通，另一条倾斜进液流道则与外接液流缓流流道连通。
作为本发明的进一步改进，液路分流腔具有样品进液口、外接液流进液口以及若干出液口，液路分流腔的样品进液口通过样品输送流道与进液腔连通，液路分流腔的外接液流进液口通过外接液流输送流道与外接液路连通；液路分流腔的出液口通过各自的液路分流支路与反应-定量腔连通；且各液路分流支路对称地分布在液路分流腔样品进液口、外接液流进液口连线的两侧；各液路分流支路的通道宽度和通道长度成反比。
作为本发明的进一步改进，所述反应-定量腔包括标记抗体置放腔以及包被抗体置放腔；包被抗体置放腔设置于反应-定量腔的中部位置处，且包被抗体置放腔具有反应池进液支路、反应池出液支路；反应-定量腔在反应池进液支路、反应池出液支路连线的两侧分别设置有一个标记抗体置放腔。
作为本发明的进一步改进，每一个反应-定量腔与相应的废液腔之间液路分流支路上均安装有阀门装置；所述阀门装置包括：
用于感测流体是否流经阀门装置安装位置的检测机构、下压机构、密封件；
在芯片本体中处于常开状态的阀门装置，在检测机构所反馈的数值表明流体流经阀门装置安装位置时，能够自动闭合，处于截流状态；
处于截流状态的阀门装置能够定时打开，处于流通状态；
处于流通状态的阀门装置，在气路提供的气流推动下，流体能够在阀门装置中流通；
所述的密封件，为导电密封圈，包括外层密封圈、内部封闭膜以及探头触点；内部封闭膜处于外层密封圈的内圈；探头触点与外层密封圈连接；
所述的下压机构，包括下压头，该下压头位于内部封闭膜的上方；
所述检测机构，包括检测探头，该检测探头与下压头联动连接，并位于探头触点的上方，同时检测探头与探头触点之间的间距小于下压头与内部封闭膜之间的间距；
阀门装置安装位置处的微流控流道通过微流控流道横隔分成微阀进液段和微阀出液段；
微阀进液段具有出液口，微阀出液段具有进液口；
内部封闭膜能够同时覆盖住微阀进液段的出液口、微阀出液段的进液口，并通过外层密封圈密封；
当下压机构的下压头带着检测探头面向导电密封圈下行时，在检测探头与探头触点相触时，下压机构停止下行，此时，下压头与内部封闭膜之间存在间距；当检测探头感测的数据出现变化，表明存在流体流经阀门装置安装位置处的微流控流道时，触发下压机构动作，推动下压头继续下行，直至下压头压住内部封闭膜，以同时封住微阀进液段的出液口、微阀出液段的进液口，此时阀门装置处于截流状态；
当下压机构的下压头与内部封闭膜之间存在间隙时，阀门装置处于打开状态，内部封闭膜所具有的形变特征，确保流体能够从微阀进液段的出液口流出，从微阀出液段的进液口流入。
作为本发明的进一步改进，废液腔分体设置为三个部分，呈半包围形状布置在芯片本体外围，包括处于芯片本体两侧的第一废液腔、第二废液腔以及将第一废液腔、第二废液腔连通的第三废液腔；其中：第一废液腔能够与第一排状反应-定量腔连通，第二废液腔能够与第二排状反应-定量腔连通。
作为本发明的进一步改进，所述第一废液腔、第二废液腔的结构一致，包括废液池a、覆盖在废液池a上方的中层盖板a以及覆盖在中层盖板a上的上层盖板a；中层盖板a在面向废液池a的板面具有容纳吸水纸的吸水纸嵌槽a，而在面向上层盖板a的板面具有若干间隔分布的导电密封圈嵌槽，导电密封圈嵌槽中安装有导电密封圈，而上层盖板a在与各导电密封圈嵌槽对应的位置处均布置有电容探头穿行孔以及下压机构下压头穿行孔；所述废液池a的内侧壁面间隔地设置有若干齿状导流件，并在靠近该齿状导流件尖端的位置处布置吸水纸定位柱；所述吸水纸定位柱与废液池a的内侧壁面之间具有的间隙形成废液池a的气体通道。
作为本发明的进一步改进，所述第三废液腔包括废液池b、覆盖在废液池b敞口端上方的中层盖板b以及覆盖在中层盖板b上方的上层盖板b；中层盖板b在面向上层盖板b的板面设置吸水纸安装槽b，且吸水纸安装槽b的槽底开设有出气孔a，而上层盖板b则在与吸水纸安装槽b的槽口相对的板面贯穿地开设出气孔b。
本发明的另一技术目的是提供一种基于主动控制液体流动的多通量微流控芯片，包括芯片本体，该芯片本体为三片式结构，包括从上到下依次布置的上层芯片、中层芯片以及下层芯片；所述下层芯片上设置有全血过滤池、反应-定量池以及废液池；中层芯片在与全血过滤池对应的位置处设置有进样槽，在与反应-定量池对应的位置处设置中层反应池通孔，在与废液池对应的位置处设置覆盖废液池敞口端的中层盖板；上层芯片在与进样槽对应的位置处设置进样槽外环，在与中层反应池通孔对应的位置处设置上层反应池通孔，在与中层盖板对应的位置处设置上层盖板；废液池分体设置为三个部分，呈半包围形状布置在芯片本体外围，包括处于芯片本体两侧的第一废液池、第二废液池以及将第一废液池、第二废液池连通的第三废液池；
下层芯片上还设置有液路分流池，该液路分流池设置在下层芯片的中间位置处，且液路分流池的一端与全血过滤池之间设置样品输送支路，另一端则与外接液路之间设置外接液流输送支路；
液路分流池通过进流机构与样品输送支路、外接液流输送支路择一连通；
进流机构包括样品进液流道、样品缓流流道、分流腔进流流道、外接液流缓流流道以及外接液流进液流道；其中：样品进液流道、外接液流进液流道均为上升流道，分流腔进流流道则为下降流道；样品进液流道的进液口通过样品输送支路与进液腔连通，出液口则依次通过样品缓流流道、分流腔进流流道与液路分流腔连通；外接液流进液流道的进液口通过外接液流输送支路与外接液路连通，另一端则依次通过外接液流缓流流道、分流腔进流流道与液路分流腔连通。
分流腔进流流道通过在进液部件嵌槽中嵌装塞体而形成，所述进液部件嵌槽包括等腰三角形嵌槽以及圆柱形外套管，所述等腰三角形嵌槽倒置，圆柱形外套管沿着等腰三角形嵌槽中线位置布置，起始于等腰三角形嵌槽的底边，并外延出等腰三角形嵌槽的顶点部位，形成分流腔进流流道的圆形出流道；塞体具有与圆柱形外套管匹配的圆柱形堵头，并以圆柱形堵头的中心线对称地设置两个倾斜外壁面，分别与等腰三角形嵌槽的两等腰斜边形成倾斜进液流道，其中一条倾斜进液流道与样品缓流流道连通，另一条倾斜进液流道则与外接液流缓流流道连通；
液路分流池在其样品输送支路、外接液流输送支路连线的两侧对称地分别布置有5条液路分流支路，各液路分流支路均与一个反应-定量池连接，且各液路 分流支路与各自连接的反应-定量池之间设置有防回流装置；另外，所述的液路分流池两侧的反应-定量池均呈排状布置，分别对应为第一排状反应-定量池、第二排状反应-定量池；第一废液池能够与第一排状反应-定量池连通；第二废液池能够与第二排状反应-定量池连通；
第一废液池、第二废液池结构一致；第一废液池的中层盖板在面向第一废液池的板面具有容纳吸水纸的吸水纸嵌槽a，而在面向第一废液池的上层盖板的板面具有若干间隔分布的导电密封圈嵌槽，导电密封圈嵌槽中安装有导电密封圈，而第一废液池的上层盖板在与各导电密封圈嵌槽对应的位置处均布置有电容探头穿行孔以及下压机构下压头穿行孔；
所述第三废液池的中层盖板在面向其上层盖板的板面设置吸水纸安装槽b，且吸水纸安装槽b的槽底开设有出气孔a，而第三废液池的上层盖板则在与吸水纸安装槽b的槽口相对的板面贯穿地开设出气孔b。
根据上述的技术方案，相对于现有技术，本发明具有如下的优点：
1、本发明创造性地将一道液路均匀分布到十道液路，同时进行10个项目的检测，大大提高产品通量。
2、本发明采用了本公司创造性设计的阀门装置、防回流装置，并结合气路作为液体向前的推动力，能随意控制流道内液体速度，并可以固定在某一区域内，进行孵育反应。达到真正的微流控目的。
3、本发明可以通过定量槽达到这种意义上的定量加样，
4、同时起到一台设备同时操作多个微流控芯片的目的。提高通量，节省时间。
附图说明
图1是本发明所述基于主动控制液体流动的微流控芯片的结构示意图；
图1中：1、上层芯片；2、中层芯片；3、下层芯片；4、气路装置；5-1、下压机构；5-2、电容探头；5-3、导电密封圈；6、液路装置；7-1、第三吸水纸；7-2、第二吸水纸；7-3、第一吸水纸；8、滤血纸；
图2是本发明所述微流控芯片的俯视图；
图2中：5、阀门装置；9-3、气路接口；9-2、加样孔；9-1、透气孔；10、芯片外定位部；11、反应-定量腔；12、出气孔；13、液路接口；14、电容探头 检测口；
图3是本发明所述下层芯片的结构示意图；
图4a是图3中A部分的放大结构示意图；
图4b是图3中A部分的俯视图；
图3、4a、4b中：3-1、反应-定量池；3-2、全血过滤池；3-2-1、全血过滤池的侧边槽壁；3-3、第二废液池；3-3-1、第二废液池的内侧壁上的锯齿状导流件；3-4、第一废液池；3-4-1、第一废液池的吸水纸固定件；3-4-2、第一废液池的内侧壁上的锯齿状导流件；3-5、第三废液池；3-6、芯片固定柱；3-7、液路分流池；
图5是本发明所述液路分流池的放大结构示意图；
图5中：3-7、液路分流池；3-7-1、样品输送流道；3-7-2至3-7-11、分流池的10条并行液路分流支路；3-7-12、外接液流(清洗液和显色液)输送流道；
图6是定量-反应池的放大结构示意图；
图6中：3-1-1、包被抗体置放池；3-1-2、标记抗体置放池；3-1-3、反应池进液支路；3-1-4、反应池出液支路；
图7是中层芯片的结构示意图；
图8是液路分流池的进液部分的结构示意图；
图7-8中：2-1、进样槽；2-2、导电密封圈嵌槽；2-3、防回流出液口；2-4、液路分流池的进液部分；2-4-1、样品进液流道；2-4-2、样品缓流流道；2-4-3、分流腔进流流道；2-4-4、外接液流缓流流道；2-4-5、外接液流进液流道；2-5、吸水纸安装槽；2-5-1、废液池在中层芯片的出气孔；2-6、定量-反应池的通孔；2-7、芯片固定柱孔；
图9a是上层芯片的俯视图；
图9b是上层芯片的仰视图；
图9c是液路分流池的进液部件的结构示意图；
图9a、图9b、图9c中：1-1、进样槽外环；1-2、电容探头穿行孔；1-3、定量-反应池盖板；1-4、下压机构穿行孔；1-5、废液池在上层芯片的出气孔；1-6、液路分流池的进液部件；
图10a是左侧废液腔一个方向的结构示意图；
图10b是左侧废液腔另一个方向的结构示意图；
图10a、图10b中：1-2、电容探头穿行孔；2-2、导电密封圈嵌槽；2-2-1、左侧废液池中吸水纸嵌槽；3-4、左侧废液池；
图11a是本发明所述右侧废液腔的结构示意图；
图11b是右侧废液腔的局部放大结构示意图；
图11c是右侧废液腔另一方向的结构示意图；
图12是前侧废液腔的结构示意图。
具体实施方式
下面将结合本发明实施例中的附图，对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。以下对至少一个示例性实施例的描述实际上仅仅是说明性的，决不作为对本发明及其应用或使用的任何限制。基于本发明中的实施例，本领域普通技术人员在没有作出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。除非另外具体说明，否则在这些实施例中阐述的部件和步骤的相对布置、表达式和数值不限制本发明的范围。同时，应当明白，为了便于描述，附图中所示出的各个部分的尺寸并不是按照实际的比例关系绘制的。对于相关领域普通技术人员已知的技术、方法和设备可能不作详细讨论，但在适当情况下，所述技术、方法和设备应当被视为授权说明书的一部分。在这里示出和讨论的所有示例中，任何具体值应被解释为仅仅是示例性的，而不是作为限制。因此，示例性实施例的其它示例可以具有不同的值。
为了便于描述，在这里可以使用空间相对术语，如“在……之上”、“在……上方”、“在……上表面”、“上面的”等，用来描述如在图中所示的一个器件或特征与其他器件或特征的空间位置关系。应当理解的是，空间相对术语旨在包含除了器件在图中所描述的方位之外的在使用或操作中的不同方位。例如，如果附图中的器件被倒置，则描述为“在其他器件或构造上方”或“在其他器件或构造之上”的器件之后将被定位为“在其他器件或构造下方”或“在其他器件或构造之下”。因而，示例性术语“在……上方”可以包括“在……上方”和“在……下方”两种方位。该器件也可以其他不同方式定位(旋转90度或处于其他方位)。
本发明公开了一种基于主动控制液体流动的多通量微流控芯片，包括芯片本体，该芯片本体包括进液腔、反应-定量腔、液路分流腔以及废液腔，进液腔能 够与外接气路连通，液路分流腔能够分别与反应-定量腔、外接液路择一连通，其中：
所述液路分流腔，布置在芯片本体的中部位置处，具有样品进液口、外接液流进液口以及若干出液口，液路分流腔的样品进液口通过样品输送流道与进液腔连通，液路分流腔的外接液流进液口通过外接液流输送流道与外接液路连通；液路分流腔的出液口通过各自的液路分流支路与反应-定量腔连通；且各液路分流支路对称地分布在液路分流腔样品进液口、外接液流进液口连线的两侧；各液路分流支路的通道宽度和通道长度成反比。
所述液路分流腔的进液口通过进流机构分别与进液腔、外接液路择一连通；进流机构包括样品进液流道、样品缓流流道、分流腔进流流道、外接液流缓流流道以及外接液流进液流道；其中：样品进液流道、外接液流进液流道均为上升流道，分流腔进流流道则为下降流道；样品进液流道的进液口通过样品输送流道与进液腔连通，出液口则依次通过样品缓流流道、分流腔进流流道与液路分流腔连通；外接液流进液流道的进液口通过外接液流输送流道与外接液路连通，另一端则依次通过外接液流缓流流道、分流腔进流流道与液路分流腔连通。
所述分流腔进流流道通过在进液部件嵌槽中嵌装塞体而形成，所述进液部件嵌槽包括等腰三角形嵌槽以及圆柱形外套管；所述等腰三角形嵌槽倒置，圆柱形外套管沿着等腰三角形嵌槽中线位置布置，起始于等腰三角形嵌槽的底边，并外延出等腰三角形嵌槽的顶点部位，形成分流腔进流流道的圆形出流道；塞体具有与圆柱形外套管匹配的圆柱形堵头，并以圆柱形堵头的中心线对称地设置两个倾斜外壁面，分别与等腰三角形嵌槽的两等腰斜边形成倾斜进液流道，其中一条倾斜进液流道与样品缓流流道连通，另一条倾斜进液流道则与外接液流缓流流道连通。
反应-定量腔包括两个以上，附图中具有10个，分两排分布在液路分流腔的两侧，分别对应为第一排状反应-定量腔、第二排状反应-定量腔；各反应-定量腔均通过各自的液路分流支路与液路分流腔的出液口连通。另外，本发明反应-定量腔包括标记抗体置放腔以及包被抗体置放腔；包被抗体置放腔设置于反应-定量腔的中部位置处，且包被抗体置放腔具有反应池进液支路、反应池出液支路；反应-定量腔在反应池进液支路、反应池出液支路连线的两侧分别设置有一个标 记抗体置放腔。
废液腔分体设置为三个部分，呈半包围形状布置在芯片本体外围，包括处于芯片本体两侧的第一废液腔、第二废液腔以及将第一废液腔、第二废液腔连通的第三废液腔；其中：第一废液腔能够与第一排状反应-定量腔连通，第二废液腔能够与第二排状反应-定量腔连通。
所述第一废液腔、第二废液腔的结构一致，包括废液池a、覆盖在废液池a上方的中层盖板a以及覆盖在中层盖板a上的上层盖板a；中层盖板a在面向废液池a的板面具有容纳吸水纸的吸水纸嵌槽a，而在面向上层盖板a的板面具有若干间隔分布的导电密封圈嵌槽，导电密封圈嵌槽中安装有导电密封圈，而上层盖板a在与各导电密封圈嵌槽对应的位置处均布置有电容探头穿行孔以及下压机构下压头穿行孔；所述废液池a的内侧壁面间隔地设置有若干齿状导流件，并在靠近该齿状导流件尖端的位置处布置吸水纸定位柱；所述吸水纸定位柱与废液池a的内侧壁面之间具有的间隙形成废液池a的气体通道。
所述第三废液腔包括废液池b、覆盖在废液池b敞口端上方的中层盖板b以及覆盖在中层盖板b上方的上层盖板b；中层盖板b在面向上层盖板b的板面设置吸水纸安装槽b，且吸水纸安装槽b的槽底开设有出气孔a，而上层盖板b则在与吸水纸安装槽b的槽口相对的板面贯穿地开设出气孔b。
每一个反应-定量腔与相应的废液腔之间的液路分流支路上均安装有阀门装置；本发明所采用的阀门装置较为具体的描述可以参见中国专利2017102131082，所述阀门装置包括：
用于感测流体是否流经阀门装置安装位置的检测机构、下压机构、密封件；
在芯片本体中处于常开状态的阀门装置，在检测机构所反馈的数值表明流体流经阀门装置安装位置时，能够自动闭合，处于截流状态；
处于截流状态的阀门装置能够定时打开，处于流通状态；
处于流通状态的阀门装置，在气路提供的气流推动下，流体能够在阀门装置中流通；
所述的密封件，为导电密封圈，包括外层密封圈、内部封闭膜以及探头触点；内部封闭膜处于外层密封圈的内圈；探头触点与外层密封圈连接；
所述的下压机构，包括下压头，该下压头位于内部封闭膜的上方；
所述检测机构，包括检测探头，该检测探头与下压头联动连接，并位于探头触点的上方，同时检测探头与探头触点之间的间距小于下压头与内部封闭膜之间的间距；
阀门装置安装位置处的微流控流道通过微流控流道横隔分成微阀进液段和微阀出液段；
微阀进液段具有出液口，微阀出液段具有进液口；
内部封闭膜能够同时覆盖住微阀进液段的出液口、微阀出液段的进液口，并通过外层密封圈密封；
当下压机构的下压头带着检测探头面向导电密封圈下行时，在检测探头与探头触点相触时，下压机构停止下行，此时，下压头与内部封闭膜之间存在间距；当检测探头感测的数据出现变化，表明存在流体流经阀门装置安装位置处的微流控流道时，触发下压机构动作，推动下压头继续下行，直至下压头压住内部封闭膜，以同时封住微阀进液段的出液口、微阀出液段的进液口，此时阀门装置处于截流状态；
当下压机构的下压头与内部封闭膜之间存在间隙时，阀门装置处于打开状态，内部封闭膜所具有的形变特征，确保流体能够从微阀进液段的出液口流出，从微阀出液段的进液口流入。
本发明所述的每一个反应-定量腔与液路分流腔之间的液路分流支路上安装有防回流装置，本发明所采用的防回流装置，较为详细的描述请参见中国专利2017102133849，包括：微流控流道和防回流结构，防回流结构位于微流控流道的上方，具有防回流流道；防回流流道能够抬升防回流结构安装位置处的微流控流道液面高度；当微流控流道接通气路时，在气路提供的气压驱动下，克服防回流流道所抬升的此处微流控流道液面高度的压力，促使防回流装置两侧的微流控流道中的流体处于流通状态。
所述防回流流道的延伸方向与防回流结构安装位置处微流控流道的延伸方向相垂直；防回流结构安装位置处的微流控流道通过微流控流道隔块分隔成两段，分别为微流控进液流道、微流控出液流道；防回流流道的上端封闭，下端则跨接在微流控流道隔块上方，并分别与微流控进液流道、微流控出液流道连通。
所述防回流流道内具有防回流凸块，且防回流凸块与防回流流道之间形成有 两条防回流连通流道；所述的两条防回流连通流道，分别与微流控进液流道、微流控出液流道连通；防回流凸块的下端与防回流流道的下端齐平，而防回流凸块的上端则低于防回流流道的上端设置。
所述防回流凸块在两条防回流连通流道之间的截面成梯形状设置。
所述微流控流道隔块为楔形块，而防回流流道为形状与微流控流道隔块形状相似的楔形槽。
防回流结构安装位置处的微流控流道，在微流控流道隔块的两侧对称地布置有楔形连接柱，防回流流道具有与楔形连接柱配合连接的楔形连接槽。
本发明所述的进液腔腔，可以参见中国专利申请2017103771423，包括全血滤样池以及封盖住全血滤样池的顶盖，进样部位设置于顶盖；该全血滤样池具有滤样出口，全血滤样池的侧壁以渐缩的方式延伸至滤样出口位置处，该呈渐缩方式延伸的侧壁呈具有引流作用的齿状设置；全血滤样池中铺设有全血滤样纸，且全血滤样纸的侧边能够与相邻的全血滤样池的齿状侧壁的各齿牙内凸尖端相触。进样部位具有环形凹槽和环形凸缘，该环形凸缘的外侧壁为环形凹槽的内侧壁，气源接口置于环形凹槽中；透气孔包括第一透气孔、第二透气孔；第一透气孔设于环形凸缘的端面，该环形凸缘通过一收敛过渡面与加样孔衔接，第二透气孔紧靠着环形凸缘的内壁设于收敛过渡面，且第二透气孔所处位置与第一透气孔所在位置相邻。
附图公开了本发明所述技术方案的一个较为详尽的实施例，具体是：
一种基于主动控制液体流动的多通量微流控芯片，如图1至12所示，包括芯片本体，该芯片本体为三片式结构，包括从上到下依次布置的上层芯片、中层芯片以及下层芯片；其中：
如图3、图4a、图4b所示，所述下层芯片上设置有全血过滤池、反应-定量池、废液池、液路分流池，其中：
废液池分体设置为三个部分，呈半包围形状布置在芯片本体外围，包括处于芯片本体两侧的第一废液池、第二废液池以及将第一废液池、第二废液池连通的第三废液池；
液路分流池设置在下层芯片的中间位置处，且液路分流池的一端与全血过滤池之间设置样品输送流道，另一端则与外接液路之间设置外接液流输送流道，用 于输送清洗液或者显色液；
液路分流池，如图5所示，设置有10条液路分流支路，在其样品输送流道、外接液流输送流道连线的两侧对称地分别布置有5条液路分流支路，各液路分流支路均与一个反应-定量池连接，且各液路分流支路与各自连接的反应-定量池之间设置有防回流装置；
反应-定量池，如图6所示，包括标记抗体置放池以及包被抗体置放池；包被抗体置放池设置于反应-定量池的中部位置处，且包被抗体置放池具有反应池进液支路、反应池出液支路；反应-定量池在反应池进液支路、反应池出液支路连线的两侧分别设置有一个标记抗体置放池。
液路分流池通过进流机构与样品输送支路、外接液流输送支路择一连通。
所述中层芯片，如图7所示，在与全血过滤池对应的位置处设置有进样槽，在与反应-定量池对应的位置处设置中层反应池通孔，在与废液池对应的位置处设置覆盖废液池敞口端的中层盖板。
进流机构，如图8所示，包括样品进液流道、样品缓流流道、分流腔进流流道、外接液流缓流流道以及外接液流进液流道；其中：样品进液流道、外接液流进液流道均为上升流道，分流腔进流流道则为下降流道；样品进液流道的进液口通过样品输送支路与进液腔连通，出液口则依次通过样品缓流流道、分流腔进流流道与液路分流腔连通；外接液流进液流道的进液口通过外接液流输送支路与外接液路连通，另一端则依次通过外接液流缓流流道、分流腔进流流道与液路分流腔连通。
分流腔进流流道通过在进液部件嵌槽中嵌装塞体而形成，所述进液部件嵌槽包括等腰三角形嵌槽以及圆柱形外套管，所述等腰三角形嵌槽倒置，圆柱形外套管沿着等腰三角形嵌槽中线位置布置，起始于等腰三角形嵌槽的底边，并外延出等腰三角形嵌槽的顶点部位，形成分流腔进流流道的圆形出流道；塞体具有与圆柱形外套管匹配的圆柱形堵头，并以圆柱形堵头的中心线对称地设置两个倾斜外壁面，分别与等腰三角形嵌槽的两等腰斜边形成倾斜进液流道，其中一条倾斜进液流道与样品缓流流道连通，另一条倾斜进液流道则与外接液流缓流流道连通。
如图9a、9b、9c所示，上层芯片在与进样槽对应的位置处设置进样槽外环，在与中层反应池通孔对应的位置处设置上层反应池通孔，在与中层盖板对应的位 置处设置上层盖板。
如图10a、10b以及如图11a至11c所述，第一废液池、第二废液池结构一致；第一废液池的中层盖板在面向第一废液池的板面具有容纳吸水纸的吸水纸嵌槽a，而在面向第一废液池的上层盖板的板面具有若干间隔分布的导电密封圈嵌槽，导电密封圈嵌槽中安装有导电密封圈，而第一废液池的上层盖板在与各导电密封圈嵌槽对应的位置处均布置有电容探头穿行孔以及下压机构下压头穿行孔；
如图12所示，所述第三废液池的中层盖板在面向其上层盖板的板面设置吸水纸安装槽b，且吸水纸安装槽b的槽底开设有出气孔a，而第三废液池的上层盖板则在与吸水纸安装槽b的槽口相对的板面贯穿地开设出气孔b。
本发明所述的液路分流池，具有如下特点：
A.1路均匀分流10路。
B.通道宽窄和通道长度成反比，利于平衡液体流动阻力。
C.液体从中间圆圈正上方往下流，均匀分布到10个流道。
D.10个流道末端加液体向上移动的阻力装置(防回流)，进一步消除各个流道的差异。
本发明所述反应-定量池，具有如下特点：
包被抗体和标记抗体物理分割，有效去除非特异结合，提高信噪比。又在同一孔内，芯片设计简单，方便。
第一废液池、第二废液池的设计，具有如下特点：
A.吸水纸吸收液体，防止漏液。
B.设置吸水纸固定柱以及齿状导流件，可以保证吸水纸没有全部填满废液池，预留气体通道，避免吸水纸内液体被吹出去。
C.锯齿状导流件避免液体从气体通道流出去。
D.废液池中层芯片段-提高废液池体积。
第三废液池的设计，具有如下特点：
A.在中层芯片设置吸水纸，消除可能的液体漏液和气泡渗出；
B.中层芯片、上层芯片设置出气孔，进一步消除可能的液体漏液和气泡渗出。
综上所述，本发明具有如下优点：
本发明设计了一种液路均匀分流装置，提高产品的通量
本发明创造性地设计了阀门装置，防回流装置，并结合气路作为液体向前的推动力，能随意控制流道内液体速度，并可以固定在某一区域内，进行孵育反应。达到真正的微流控目的
本发明在废液池内加入吸水材质，起到防止废液外溅的作用，同时巧妙的设计了气体通道，锯齿状导流装置，中层芯片吸水纸等装置有效避免了液体漏液。使生产工艺简单实用。
本发明通过有导电橡胶制成的密封圈，和设备电容检测探头一起起到，液体流动状态的检测。
本发明将定量槽，标记物槽和反应槽合三为一，既可以有效定量加样，同时又能将标记抗体和包被抗体放置在同一槽内的不同区域，有效避免非特异结合，提高信噪比，同时设计简单实用。
本发明通过液路连接芯片，清洗反应槽，有效降低反应本底，提高产品灵敏度。

Claims (10)

  1. 一种基于主动控制液体流动的多通量微流控芯片，包括芯片本体，该芯片本体包括进液腔、反应-定量腔以及废液腔，进液腔能够与外接气路连通，其特征在于，还包括液路分流腔，所述液路分流腔布置在芯片本体的中部位置处；反应-定量腔包括两个以上，呈排状分布在液路分流腔的两侧，分别对应为第一排状反应-定量腔、第二排状反应-定量腔；各反应-定量腔均通过各自的液路分流支路与液路分流腔的出液口连通，而液路分流腔的进液口则能够分别与进液腔的出液口以及外接液路连通。
  2. 根据权利要求1所述的基于主动控制液体流动的多通量微流控芯片，其特征在于，所述液路分流腔的进液口通过进流机构分别与进液腔、外接液路择一连通；进流机构包括样品进液流道、样品缓流流道、分流腔进流流道、外接液流缓流流道以及外接液流进液流道；其中：样品进液流道、外接液流进液流道均为上升流道，分流腔进流流道则为下降流道；样品进液流道的进液口通过样品输送流道与进液腔连通，出液口则依次通过样品缓流流道、分流腔进流流道与液路分流腔连通；外接液流进液流道的进液口通过外接液流输送流道与外接液路连通，另一端则依次通过外接液流缓流流道、分流腔进流流道与液路分流腔连通。
  3. 根据权利要求2所述的基于主动控制液体流动的多通量微流控芯片，其特征在于，所述分流腔进流流道通过在进液部件嵌槽中嵌装塞体而形成，所述进液部件嵌槽包括等腰三角形嵌槽以及圆柱形外套管；所述等腰三角形嵌槽倒置，圆柱形外套管沿着等腰三角形嵌槽中线位置布置，起始于等腰三角形嵌槽的底边，并外延出等腰三角形嵌槽的顶点部位，形成分流腔进流流道的圆形出流道；塞体具有与圆柱形外套管匹配的圆柱形堵头，并以圆柱形堵头的中心线对称地设置两个倾斜外壁面，分别与等腰三角形嵌槽的两等腰斜边形成倾斜进液流道，其中一条倾斜进液流道与样品缓流流道连通，另一条倾斜进液流道则与外接液流缓流流道连通。
  4. 根据权利要求1所述的基于主动控制液体流动的多通量微流控芯片，其特征在于，液路分流腔具有样品进液口、外接液流进液口以及若干出液口，液路分流腔的样品进液口通过样品输送流道与进液腔连通，液路分流腔的外接液流进液口通过外接液流输送流道与外接液路连通；液路分流腔的出液口通过 各自的液路分流支路与反应-定量腔连通；且各液路分流支路对称地分布在液路分流腔样品进液口、外接液流进液口连线的两侧；各液路分流支路的通道宽度和通道长度成反比。
  5. 根据权利要求1所述的基于主动控制液体流动的多通量微流控芯片，其特征在于，所述反应-定量腔包括标记抗体置放腔以及包被抗体置放腔；包被抗体置放腔设置于反应-定量腔的中部位置处，且包被抗体置放腔具有反应池进液支路、反应池出液支路；反应-定量腔在反应池进液支路、反应池出液支路连线的两侧分别设置有一个标记抗体置放腔。
  6. 根据权利要求1所述的基于主动控制液体流动的多通量微流控芯片，其特征在于，每一个反应-定量腔与相应的废液腔之间的微流控流道上均安装有阀门装置；所述阀门装置包括：
    用于感测流体是否流经阀门装置安装位置的检测机构、下压机构、密封件；
    在芯片本体中处于常开状态的阀门装置，在检测机构所反馈的数值表明流体流经阀门装置安装位置时，能够自动闭合，处于截流状态；
    处于截流状态的阀门装置能够定时打开，处于流通状态；
    处于流通状态的阀门装置，在气路提供的气流推动下，流体能够在阀门装置中流通；
    所述的密封件，为导电密封圈，包括外层密封圈、内部封闭膜以及探头触点；内部封闭膜处于外层密封圈的内圈；探头触点与外层密封圈连接；
    所述的下压机构，包括下压头，该下压头位于内部封闭膜的上方；
    所述检测机构，包括检测探头，该检测探头与下压头联动连接，并位于探头触点的上方，同时检测探头与探头触点之间的间距小于下压头与内部封闭膜之间的间距；
    阀门装置安装位置处的微流控流道通过微流控流道横隔分成微阀进液段和微阀出液段；
    微阀进液段具有出液口，微阀出液段具有进液口；
    内部封闭膜能够同时覆盖住微阀进液段的出液口、微阀出液段的进液口，并通过外层密封圈密封；
    当下压机构的下压头带着检测探头面向导电密封圈下行时，在检测探头与探头触点相触时，下压机构停止下行，此时，下压头与内部封闭膜之间存在间距；当检测探头感测的数据出现变化，表明存在流体流经阀门装置安装位置处的微流控流道时，触发下压机构动作，推动下压头继续下行，直至下压头压住内部封闭膜，以同时封住微阀进液段的出液口、微阀出液段的进液口，此时阀门装置处于截流状态；
    当下压机构的下压头与内部封闭膜之间存在间隙时，阀门装置处于打开状态，内部封闭膜所具有的形变特征，确保流体能够从微阀进液段的出液口流出，从微阀出液段的进液口流入。
  7. 根据权利要求1所述的基于主动控制液体流动的多通量微流控芯片，其特征在于，废液腔分体设置为三个部分，呈半包围形状布置在芯片本体外围，包括处于芯片本体两侧的第一废液腔、第二废液腔以及将第一废液腔、第二废液腔连通的第三废液腔；其中：第一废液腔能够与第一排状反应-定量腔连通，第二废液腔能够与第二排状反应-定量腔连通。
  8. 根据权利要求7所述的基于主动控制液体流动的多通量微流控芯片，其特征在于，所述第一废液腔、第二废液腔的结构一致，包括废液池a、覆盖在废液池a上方的中层盖板a以及覆盖在中层盖板a上的上层盖板a；中层盖板a在面向废液池a的板面具有容纳吸水纸的吸水纸嵌槽a，而在面向上层盖板a的板面具有若干间隔分布的导电密封圈嵌槽，导电密封圈嵌槽中安装有导电密封圈，而上层盖板a在与各导电密封圈嵌槽对应的位置处均布置有电容探头穿行孔以及下压机构下压头穿行孔；所述废液池a的内侧壁面间隔地设置有若干齿状导流件，并在靠近该齿状导流件尖端的位置处布置吸水纸定位柱；所述吸水纸定位柱与废液池a的内侧壁面之间具有的间隙形成废液池a的气体通道。
  9. 根据权利要求7或8所述的基于主动控制液体流动的多通量微流控芯片，其特征在于，所述第三废液腔包括废液池b、覆盖在废液池b敞口端上方的中层盖板b以及覆盖在中层盖板b上方的上层盖板b；中层盖板b在面向上层盖板b的板面设置吸水纸安装槽b，且吸水纸安装槽b的槽底开设有出气孔a，而上层盖板b则在与吸水纸安装槽b的槽口相对的板面贯穿地开设出气孔b。
  10. 一种基于主动控制液体流动的多通量微流控芯片，包括芯片本体，该芯片本体为三片式结构，包括从上到下依次布置的上层芯片、中层芯片以及下层芯片；所述下层芯片上设置有全血过滤池、反应-定量池以及废液池；中层芯片在与全血过滤池对应的位置处设置有进样槽，在与反应-定量池对应的位置处设置中层反应池通孔，在与废液池对应的位置处设置覆盖废液池敞口端的中层盖板；上层芯片在与进样槽对应的位置处设置进样槽外环，在与中层反应池通孔对应的位置处设置上层反应池通孔，在与中层盖板对应的位置处设置上层盖板；其特征在于，废液池分体设置为三个部分，呈半包围形状布置在芯片本体外围，包括处于芯片本体两侧的第一废液池、第二废液池以及将第一废液池、第二废液池连通的第三废液池；
    下层芯片上还设置有液路分流池，该液路分流池设置在下层芯片的中间位置处，且液路分流池的一端与全血过滤池之间设置样品输送支路，另一端则与外接液路之间设置外接液流输送支路；
    液路分流池通过进流机构与样品输送支路、外接液流输送支路择一连通；
    进流机构包括样品进液流道、样品缓流流道、分流腔进流流道、外接液流缓流流道以及外接液流进液流道；其中：样品进液流道、外接液流进液流道均为上升流道，分流腔进流流道则为下降流道；样品进液流道的进液口通过样品输送支路与进液腔连通，出液口则依次通过样品缓流流道、分流腔进流流道与液路分流腔连通；外接液流进液流道的进液口通过外接液流输送支路与外接液路连通，另一端则依次通过外接液流缓流流道、分流腔进流流道与液路分流腔连通。
    分流腔进流流道通过在进液部件嵌槽中嵌装塞体而形成，所述进液部件嵌槽包括等腰三角形嵌槽以及圆柱形外套管，所述等腰三角形嵌槽倒置，圆柱形外套管沿着等腰三角形嵌槽中线位置布置，起始于等腰三角形嵌槽的底边，并外延出等腰三角形嵌槽的顶点部位，形成分流腔进流流道的圆形出流道；塞体具有与圆柱形外套管匹配的圆柱形堵头，并以圆柱形堵头的中心线对称地设置两个倾斜外壁面，分别与等腰三角形嵌槽的两等腰斜边形成倾斜进液流道，其中一条倾斜进液流道与样品缓流流道连通，另一条倾斜进液流道则与外接液流缓流流道连通；
    液路分流池在其样品输送支路、外接液流输送支路连线的两侧对称地分别布置有5条液路分流支路，各液路分流支路均与一个反应-定量池连接，且各液路分流支路与各自连接的反应-定量池之间设置有防回流装置；另外，所述的液路分流池两侧的反应-定量池均呈排状布置，分别对应为第一排状反应-定量池、第二排状反应-定量池；第一废液池能够与第一排状反应-定量池连通；第二废液池能够与第二排状反应-定量池连通；
    第一废液池、第二废液池结构一致；第一废液池的中层盖板在面向第一废液池的板面具有容纳吸水纸的吸水纸嵌槽a，而在面向第一废液池的上层盖板的板面具有若干间隔分布的导电密封圈嵌槽，导电密封圈嵌槽中安装有导电密封圈，而第一废液池的上层盖板在与各导电密封圈嵌槽对应的位置处均布置有电容探头穿行孔以及下压机构下压头穿行孔；
    所述第三废液池的中层盖板在面向其上层盖板的板面设置吸水纸安装槽b，且吸水纸安装槽b的槽底开设有出气孔a，而第三废液池的上层盖板则在与吸水纸安装槽b的槽口相对的板面贯穿地开设出气孔b。
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