WO2021077590A1 - Microfluidic control chip and in vitro detection apparatus - Google Patents

Microfluidic control chip and in vitro detection apparatus Download PDF

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Publication number
WO2021077590A1
WO2021077590A1 PCT/CN2019/126899 CN2019126899W WO2021077590A1 WO 2021077590 A1 WO2021077590 A1 WO 2021077590A1 CN 2019126899 W CN2019126899 W CN 2019126899W WO 2021077590 A1 WO2021077590 A1 WO 2021077590A1
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channel
flow channel
micro
cavity
quantitative
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PCT/CN2019/126899
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French (fr)
Chinese (zh)
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白孟斌
万惠芳
冷杰
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广州万孚生物技术股份有限公司
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Publication of WO2021077590A1 publication Critical patent/WO2021077590A1/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
    • 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
    • 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
    • B01L3/502753—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 bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation
    • 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
    • B01L3/502761—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 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules
    • 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
    • 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
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0409—Moving fluids with specific forces or mechanical means specific forces centrifugal forces

Definitions

  • This application relates to the field of in vitro diagnostic technology, for example, to a microfluidic chip and an in vitro detection device.
  • In Vitro Diagnosis belongs to the pharmaceutical and biological industry, which refers to taking blood, body fluids, tissues and other samples from the human body, and using in vitro testing reagents, instruments, etc. to test and verify the samples in order to prevent diseases , Diagnosis, treatment testing, late-stage observation, health evaluation, genetic disease prediction, etc.
  • In vitro diagnosis is divided into three categories: biochemical diagnosis, immunodiagnosis and molecular diagnosis according to methodology, as well as point-of-care testing (POCT) differentiated from biochemical, immunological and molecular diagnosis.
  • POCT point-of-care testing
  • Dry chemical reaction is a type of biochemical diagnosis, which uses biochemical reagents to react with a specific substrate, and then quantitatively detects the concentration of the target through an instrument to calculate certain biochemical indicators of the human body.
  • Traditional biochemical diagnosis needs to be tested on a large-scale biochemical analyzer, which leads to high reagent consumption and insufficient flexibility.
  • the general dry-type biochemical POCT diagnosis method has a low test throughput, and generally only one or a few tests can be tested at a time. Samples, one or several items.
  • Microfluidics technology can integrate basic operation units such as sample preparation, reaction, separation, and detection in biological, chemical, and medical analysis processes on the chip, automatically completing the entire analysis process, greatly improving the detection efficiency, and at the same time It has the advantages of miniaturization and automation, so it is more and more widely used in the field of POCT.
  • the embodiments of the present application provide a microfluidic chip capable of improving sample processing efficiency and an in vitro detection device containing the microfluidic chip.
  • a microfluidic chip has a sample loading cavity, a first microfluidic channel, a second microfluidic channel, a separation and quantitative unit, a first capillary channel and a first waste liquid cavity;
  • the sample loading cavity has a A sample hole, the sample loading cavity is communicated with the second microchannel through the first microchannel;
  • the microfluidic chip has a center of rotation, and the second microchannel is arranged around the center of rotation
  • the first waste liquid cavity communicates with the outlet end of the second micro-channel through the first capillary channel; there are multiple separation and quantitative units, and each of the separation and quantitative units includes a third micro-channel A flow channel, a quantitative cavity and a second waste liquid cavity, the quantitative cavity is in communication with the second micro flow channel through the third micro flow channel, and the second waste liquid cavity is connected to the quantitative cavity Body is connected, a plurality of the separation and quantification units are distributed around the second micro flow channel on the inner side of the second micro flow channel; the first capillary flow channel is self-con
  • An in vitro detection device includes the microfluidic chip described in any one of the above embodiments and a detection mechanism, the detection mechanism is in communication with a quantitative cavity, and the detection mechanism is configured to detect a sample in the quantitative cavity.
  • Figure 1 Figure 1 and Figure 3 are schematic diagrams of the front, back, and side structures of a microfluidic chip according to an embodiment of the application, respectively.
  • Figure 4-1, Figure 4-2, Figure 4-3, Figure 4-4 are schematic diagrams of the separation and quantification flow of the sample solution by the microfluidic chip shown in Figure 1, Figure 4-3-1, Figure 4-3 -2 is a partial enlarged schematic diagram.
  • Figure 5-1 and Figure 5-2 are respectively a schematic diagram of the detection process of the microfluidic chip shown in Figure 1, and Figure 5-1-1 is a partial enlarged schematic diagram.
  • an embodiment of the present application provides a microfluidic chip 10, which has a sample loading cavity 11, a first micro flow channel 12, a second micro flow channel 13, a separation and quantification unit 14, The first capillary flow channel 15 and the first waste liquid cavity 16.
  • the sample loading cavity 11 has a sample loading hole 111.
  • the sample solution can be added into the sample adding cavity 11 from the sample adding hole 111.
  • the sample application cavity 11 communicates with the second micro flow channel 13 through the first micro flow channel 12.
  • the microfluidic chip 10 has a rotation center 101. When rotating and centrifuging, the microfluidic chip 10 rotates with the rotation center 101 as the center of the circle.
  • the second micro flow channel 13 is arranged around the center of rotation 101.
  • the first waste liquid cavity 16 communicates with the liquid outlet end of the second micro flow channel 13 through the first capillary flow channel 15.
  • Each separation and quantitative unit 14 includes a third micro flow channel 141, a quantitative cavity 142 and a second waste liquid cavity 143. Wherein, the quantitative cavity 142 communicates with the second micro channel 13 through the third micro channel 141, and the second waste liquid cavity 143 communicates with the quantitative cavity 142.
  • the multiple separation and quantitative units 14 are distributed around the second micro flow channel 13 inside the second micro flow channel 13.
  • a plurality of separation and quantitative units 14 are evenly spaced and distributed around the second micro flow channel 13.
  • the "surround” described herein may be a closed ring or not, for example, it may be surrounded in a fan shape with an angle greater than 180°.
  • the first capillary flow channel 15 is connected to the second micro flow channel 13 in the inner side of the second micro flow channel 13 in a direction approaching the rotation center 101 (may be a direction gradually approaching the rotation center 101, For example, it may be, but not limited to, extend and bend in a direction away from the rotation center 101 (may be each gradually away from the rotation center 101, for example, but not limited to a diameter away from the rotation center 101). It extends toward) to communicate with the first waste liquid cavity 16.
  • the third micro flow channel 141 is located inside the second micro flow channel 13, and the third micro flow channel 141 extends in a direction close to the rotation center 101 after being connected to the second micro flow channel 13 to communicate with the quantitative cavity 142.
  • the distance between the connection position of the quantitative cavity 142 and the third micro flow channel 141 from the rotation center 101 is greater than or equal to the distance between the bending apex position of the first capillary flow channel 15 and the rotation center 101, and the second waste The liquid cavity 143 is farther away from the rotation center 101 than the quantitative cavity 142.
  • the sample solution can be separated and quantified in one centrifugation, and the sample solution can be distributed to multiple separation and quantification units 14 with good consistency and high integration, which significantly improves the unit The throughput of the test.
  • the sample addition cavity 11 is arranged around the center of rotation 101, one end is provided with a sample addition hole 111, and the other end is connected to the first micro flow channel 12, and optionally, the sample addition cavity 11 is provided with its own sample addition
  • the hole 111 gradually widens from one end to the other end, so that the added sample solution can flow smoothly to the first micro-channel 12.
  • the end of the sample adding cavity 11 connected with the first micro flow channel 12 extends in a direction away from the rotation center 101, and is connected to the first micro flow channel 12 at the bottom, so that the sample solution can be introduced into the first micro flow channel during centrifugation. Road 12.
  • the sample adding cavity 11 is further provided with a first vent 112 at one end connected to the first microfluidic channel 12.
  • the first vent 112 is larger than the one between the sample loading cavity 11 and the first microfluidic channel 12.
  • the connection position is closer to the center of rotation 101.
  • one end of the second micro flow channel 13 is connected to the first micro flow channel 12 and extends around the center of rotation 101 to the other end to be connected to the first capillary flow channel 15.
  • the microfluidic chip 10 further includes a fourth microfluidic channel 17.
  • the first capillary flow channel 15 is connected to the second micro flow channel 13 through the fourth micro flow channel 17, and the fourth micro flow channel 17 is connected to the second micro flow channel 13 and extends in a direction close to the rotation center 101 to be connected to the first micro flow channel.
  • the capillary flow channel 15 is connected.
  • the microfluidic chip 10 further includes a fifth microfluidic channel 18.
  • One end of the fifth microfluidic channel 18 is connected to the first waste liquid cavity 16, and the other end has a second vent 181.
  • the second vent 181 is closer to the rotation center 101 than the first waste liquid cavity 16.
  • the fifth micro channel 18 extends in a direction close to the rotation center 101 after being connected to the first waste liquid cavity 16.
  • the first waste liquid cavity 16 is arranged around the center of rotation 101 on the outside of the second micro flow channel 13, and the volume of the entire first waste liquid cavity 16 is ensured to be large enough to fully contain the excess sample solution.
  • the radial dimension of a section of the fifth micro flow channel 18 connected to the first waste liquid cavity 16 is larger than that of the section close to the second vent 181 to prevent liquid from entering the fifth micro flow channel The fifth micro-channel 18 is blocked in the middle of 18 and the ventilation is not timely.
  • each separation and quantification unit 14 further includes a sixth micro flow channel 146.
  • the quantitative cavity 142 communicates with the third micro flow channel 141 through the sixth micro flow channel 146.
  • connection position of the sixth micro flow channel 146 and the third micro flow channel 141 is closer to the rotation center 101 than the quantitative cavity 142.
  • the distance between the connection position of the sixth micro flow channel 146 and the third micro flow channel 141 from the rotation center 101 is greater than or equal to the distance between the bending apex position of the first capillary flow channel 15 and the rotation center 101.
  • the microfluidic chip 10 further includes a gas-permeable microfluidic channel 19.
  • the air-permeable micro flow channel 19 communicates with the sixth micro flow channel 146 of each quantitative cavity 142.
  • a third air hole 191 is provided on the air-permeable micro flow channel 19.
  • the air-permeable micro flow channel 19 is closer to the rotation center 101 than the connection position of the sixth micro flow channel 146 and the third micro flow channel 141.
  • the gas-permeable micro flow channel 19 is annularly arranged on the inner side of the plurality of separation and quantitative units 14 around the rotation center 101.
  • one end of the sixth micro flow channel 146 is connected to the gas-permeable micro flow channel 19, the other end is connected to the quantitative cavity 142, and the third micro flow channel 141 is connected to the middle of the sixth micro flow channel 146.
  • the "middle” mentioned herein can be, but is not limited to, the center or midpoint in a geometric sense, or a position close to the center or midpoint, and optionally a non-end position.
  • each separation and quantification unit 14 further includes a seventh micro flow channel 147.
  • the second waste liquid cavity 143 communicates with the quantitative cavity 142 through the seventh micro flow channel 147.
  • the liquid outlet micro channel 144 is connected to the seventh micro channel 147.
  • the separation and quantification unit 14 further includes a liquid outlet microchannel 144.
  • One end of the liquid outlet microchannel 144 communicates with the quantitative cavity 142, and the other end is provided with a permeation hole 145.
  • the quantitative sample solution in the quantitative cavity 142 can be exuded through the penetration hole 145.
  • the liquid outlet microchannel 144 includes a second capillary channel 148.
  • One end of the second capillary channel 148 communicates with the seventh micro channel 147, and the other end is provided with a permeation hole 145.
  • the second capillary channel 148 is connected to the seventh micro channel 147 and extends in a direction close to the rotation center 101, and after bending, it extends in a direction away from the rotation center 101, and the quantitative cavity 142 and the third
  • the distance between the connection position of the micro flow channel 141 and the rotation center 101 is greater than the distance between the bending apex position of the second capillary channel 148 and the rotation center 101, and the distance between the bending apex position of the first capillary channel 15 and the rotation center 101 is greater than The distance between the bending vertex position of the second capillary flow channel 148 and the rotation center 101.
  • the second capillary flow channel 148 can function as a valve and achieve a closed effect when the sample solution is separated and quantified.
  • the liquid outlet microchannel 144 further includes an eighth microchannel 149.
  • the eighth micro flow channel 149 is connected to the middle of the seventh micro flow channel 147, and the second capillary flow channel 148 communicates with the seventh micro flow channel 147 through the eighth micro flow channel 149.
  • the middle part of the microfluidic chip 10 is also provided with a mounting part 102.
  • the center of the mounting portion 102 is the rotation center 101 of the microfluidic chip 10.
  • the capillary flow channel described herein is a flow channel structure having a smaller size (e.g., width and/or depth) than the micro flow channel.
  • the first capillary flow channel 15 and the second capillary flow channel 148 are V-shaped, and the bent portion thereof is close to the rotation center 101.
  • the width of the first capillary flow channel 15 and the second capillary flow channel 148 is 0.1 mm to 0.2 mm, and the depth is 0.1 mm to 0.2 mm; or the width of the first capillary flow channel 15 and the second capillary flow channel 148 It is 0.2mm ⁇ 0.5mm, and the depth is 0.2mm ⁇ 0.5mm.
  • the width of the first capillary channel 15 and the second capillary channel 148 is 0.1mm ⁇ 0.2mm, and the depth is 0.1mm ⁇ 0.2mm, no surface treatment is required.
  • the flow channels of the first capillary flow channel 15 and the second capillary flow channel 148 may preferably be surface-treated with PEG4000.
  • the width of the first capillary flow channel 15 and the second capillary flow channel 148 is 0.2 mm, and the depth is also 0.2 mm.
  • the sample solution can flow to the other end of the sample solution by capillary action.
  • the first capillary flow channel 15 and the second capillary flow channel 148 have different sizes in different sections, for example, the width of the first capillary flow channel 15 and the second capillary flow channel 148 at the bending part is 0.2 mm, The depth is also 0.2mm, the width of other parts is 0.5mm, and the depth is also 0.2mm, in order to facilitate the flow of liquid and the formation of siphon and capillary action locally.
  • the PEG4000 surface treatment can be, but is not limited to, adding a 1wt% PEG4000 solution to the capillary flow channel and forming it after natural drying.
  • PEG4000 surface treatment is beneficial to increase the capillary force of the capillary flow channel, and PEG4000 is an inert substance in the reaction system, and generally does not react with samples and detection reagents, so it will not affect the test results.
  • the microfluidic chip 10 includes a chip body 103 and a transparent cover film 104 covering the chip body 103.
  • the chip body 103 and the transparent cover film 104 cooperate to form various cavity structures and flow channel structures.
  • the grooves of each cavity structure and flow channel structure are pre-formed on the chip body 103, as shown in FIG. 2, each hole is opened on the back of the chip body 103, and each cavity structure and flow channel
  • the groove of the structure is opened on the front surface of the chip body 103, and subsequently covered by a transparent cover film 104 and sealed on the front surface of the chip body 103 to complete the packaging of the cavity structure and the flow channel structure, forming a complete cavity structure and Runner structure.
  • the transparent cover film 104 can be, but is not limited to, a transparent tape or a transparent pressure-sensitive adhesive film, etc., which cooperates with the chip body 103 to form the entire microfluidic chip 10, which is simple to assemble and does not need to use complex and expensive ultrasonic welding technology. Yes, the production cost can be significantly reduced. It can be understood that, in other examples, the microfluidic chip 10 may also be formed by welding with a relatively high-cost ultrasonic welding technology, or be integrally formed with a 3D printing technology.
  • the application also provides an in vitro detection device, which includes the above-mentioned microfluidic chip 10 and a detection mechanism.
  • the detection mechanism communicates with the quantitative cavity 142, for example, but not limited to, communicates with the quantitative cavity 142 through the permeation hole 145.
  • the detection mechanism is configured to detect the sample in the quantitative cavity 142.
  • the detection mechanism is a dry chemical test paper.
  • the dry chemical test paper may include a support layer and a reaction indicator layer and a diffusion layer sequentially stacked on the support layer.
  • the reaction indicator layer contains a reaction reagent and an indicator reagent capable of reacting with the target substance in the sample to be tested.
  • the layer faces the permeation hole 145 through the injection port. It can be understood that, in other examples, the detection mechanism is not limited to dry chemical test paper, and may also be various other test paper strips or reactors.
  • the microfluidic chip 10 is provided with installation grooves 20 around the permeation holes 145 of each separation and quantitative unit 14, and the detection mechanism is embedded in each installation groove 20.
  • the microfluidic chip 10 can realize the separation and quantification of impurities in the sample solution by one centrifugation, such as the separation and quantification of blood cells and serum (plasma) of a whole blood sample, and the valve function of the second capillary flow channel 148 , To achieve simultaneous sample loading detection of different separation and quantification units 14. Therefore, the in vitro detection device using the microfluidic chip 10 can realize the detection of different indexes of the sample or the repeated detection of the same index by loading the sample at one time.
  • Each separation and quantification unit 14 is arranged around the center of rotation 101 and has a high degree of integration. By using the in vitro detection device, the consistency, accuracy and reliability of the detection result can be improved.
  • the process can refer to but is not limited to the following:
  • the microfluidic chip 10 is installed in an instrument with a rotating centrifugal function through its mounting part 102, the instrument is turned on, and the microfluidic chip 10 is centrifuged at a speed not limited to 4000-6000 rpm.
  • the sample solution starts to flow, from one end of the sample loading chamber 11 to the other end, and enters the annular second microchannel 13 through the first microchannel 12 .
  • the sample solution sequentially enters the third micro-channel 141, the sixth micro-channel 146, the quantitative cavity 142, and the seventh micro-channel 147 of the separation and quantitative unit 14
  • these channels and the cavity constitute the structure of the communicating device, and the air in the original channel and the cavity is self-permeable micro channel
  • the third ventilation hole 191 of 19 is discharged.
  • the sample solution fills the quantitative cavity 142 to the junction of the third microchannel 141 and the sixth microchannel 146, the sample solution also enters the second through the eighth microchannel 149.
  • the centrifugal force is greater than the hair suction force.
  • the sample solution will not rise to the bending part 148b of the second capillary flow channel 148, nor will it cause a siphon effect in the second capillary flow channel 148 to pass through After section 148c, it flows out from the permeation hole 145. At this point, the quantification of the sample solution is completed.
  • the sample solution enters the first capillary channel 15 through the second microchannel 13 and the fourth microchannel 17, and the sample solution continues to advance after passing through the 15a section.
  • the distance between the bent apex of a capillary channel 15 and the center of rotation 101 is the same as the distance between the connection part of the third micro channel 141 and the sixth micro channel 146 and the center of rotation 101, so the sample solution can reach the highest point 15b
  • the first capillary channel 15 is filled, and under the action of centrifugal force, a continuous siphon effect is formed, and the excess sample solution is continuously discharged to the first waste In the liquid chamber 16, this can improve the accuracy of quantification and avoid cross-contamination of the sample solution.
  • the fixed impurities such as blood cells of a whole blood sample
  • the fixed impurities in the quantitative cavity 142
  • the fixed impurities finally enter the second waste liquid chamber In the body 143, the impurities in the sample solution and the solution to be tested are separated in this way.
  • the microfluidic chip 10 requires only one centrifugal operation in the separation of impurities in the sample solution from the solution to be tested and the quantification of the solution to be tested.
  • the valve function of the second capillary channel 148 is used in the separation and quantification of the sample solution. At this time, the sample solution can be closed in the quantitative cavity 142 and the second waste liquid cavity 143 without flowing out.
  • the microfluidic chip 10 uses the second capillary channel 148 as a valve to control the contact reaction between the sample and the detection mechanism, which can replace the traditional water-soluble membrane or valve and other delayed opening mechanisms, making the sampling and detection process more stable and reliable. At the same time, the chip assembly process is simplified, which helps reduce production costs.
  • the above microfluidic chip is designed by designing a sample addition cavity, a first microfluidic channel, a second microfluidic channel, a plurality of separation and quantitative units, a first capillary channel and a first waste liquid cavity, wherein the first microfluidic channel , The second micro flow channel, the third micro flow channel and the first capillary flow channel of each separation and quantitative unit constitute the structure of the communicating device. After adding the sample solution to the sample loading chamber, by rotating and centrifuging, the sample solution enters the second micro flow channel through the first micro flow channel, and splits into the third micro flow of each separation and quantification unit in the second micro flow channel.
  • the sample solution will enter the quantitative cavity under the action of centrifugation, and fill the second waste liquid cavity and the quantitative cavity in turn.
  • solid wastes such as blood cells can be centrifuged and deposited to the second fluid chamber connected to the quantitative cavity.
  • the separation of whole blood and other samples and the quantification in the quantitative chamber are realized.
  • the excess sample solution enters the first capillary flow channel through the second micro flow channel.
  • the distance between the connection position of the third microchannel and the center of rotation of the microfluidic chip is equal to the distance between the bending apex of the first capillary channel and the center of rotation, so that when the sample solution reaches the bending apex of the first microchannel The time will continue to advance, and under the action of centrifugal force, a siphon effect is formed, and the excess sample solution is introduced into the first waste liquid chamber.
  • the microfluidic chip only needs one centrifugation after adding the sample solution to separate and quantify the impurities in the sample solution and the target detection solution. There is no need for excessive centrifugation, so the operation is simple, the waiting time is short, and the sample processing The efficiency is significantly improved.
  • the microfluidic chip is also designed with a liquid outlet microchannel including a second capillary channel.
  • One end of the second capillary channel is connected with the seventh microchannel, and the other end is provided with a permeation hole.
  • the second capillary channel is free from After the seventh micro-channel is connected, it extends in the direction close to the center of rotation and after bending, it extends in the direction away from the center of rotation, and the distance between the connection position of the quantitative cavity and the third micro-channel from the center of rotation is greater than that of the second capillary channel
  • the distance between the bending apex position and the center of rotation so that during centrifugation, because the centrifugal force is greater than the capillary suction force, the sample solution will not break through the bending position of the second capillary channel, and the second capillary channel can act as a "
  • the function of the “valve” closes the sample solution in the quantitative chamber without flowing out; after the subsequent centrifugation, the liquid in the second ca
  • the liquid After the liquid continues to flow to the permeable hole, it can seep out from the permeable hole. Optionally, it can be combined with low-speed centrifugation, under the action of siphon, the liquid continuously seeps from the permeable hole to the detection mechanism to complete the detection of the sample.
  • the second capillary flow channel is used as a valve to control the contact reaction between the sample and the detection mechanism, which can replace the traditional water-soluble membrane or valve and other delayed opening mechanisms, making the sampling detection process more stable and reliable, and simplifying the chip assembly process. Conducive to reducing production costs.

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Abstract

A microfluidic control chip (10) capable of increasing sample processing efficiency and an in vitro detection apparatus comprising said microfluidic control chip (10). The microfluidic control chip (10) is designed with a sampling cavity (11), a first micro flow channel (12), a second micro flow channel (13), a plurality of separating and quantifying units (14), a first capillary flow channel (15), and a first waste liquid cavity (16); after a sample solution is added into the sampling cavity (11), by means of rotation and centrifugation, the sample solution enters a quantifying cavity (142) under the action of centrifugation, and sequentially fills a second waste liquid cavity (143) and the quantifying cavity (142); by means of the centrifugation, solid waste such as blood cells can be centrifugally deposited in the second waste liquid cavity (143) in communication with the quantifying cavity (142), implementing the separation of samples such as whole blood and quantification in the quantifying cavity (142).

Description

微流控芯片及体外检测装置Microfluidic chip and in vitro detection device
本申请要求在2019年10月21日提交中国专利局、申请号为201911000623.8的中国专利申请的优先权，该申请的全部内容通过引用结合在本申请中。This application claims the priority of a Chinese patent application filed with the Chinese Patent Office with application number 201911000623.8 on October 21, 2019. The entire content of this application is incorporated into this application by reference.
技术领域Technical field
本申请涉及体外诊断技术领域，例如涉及一种微流控芯片及体外检测装置。This application relates to the field of in vitro diagnostic technology, for example, to a microfluidic chip and an in vitro detection device.
背景技术Background technique
体外诊断行业(In Vitro Diagnosis，IVD)属于医药生物行业，是指将血液、体液、组织等样本从人体中取出，使用体外检测试剂、仪器等对样本进行检测与校验，以便对疾病进行预防、诊断、治疗检测、后期观察、健康评价、遗传疾病预测等。体外诊断按照方法学分为生化诊断、免疫诊断和分子诊断三大类，以及从生化、免疫和分子诊断中分化出来的床旁快速诊断(Point-of-Care Testing，POCT)。干化学反应是生化诊断的一种，是利用生化试剂与特定的底物反应，再通过仪器定量检测出标的物浓度，推算出人体的某些生化指标。传统生化诊断需要在大型生化仪上进行检测，由此导致试剂消耗多、灵活性不够等情况；一般的干式生化POCT诊断方式则在测试通量上较低，一般一次只能测验一个或几个样本、一个或几个项目。微流控芯片技术(Microfluidics)能把生物、化学、医学分析过程的样品制备、反应、分离、检测等基本操作单元集成在芯片上，自动完成分析全过程，极大的提高了检测效率，同时具有小型化、自动化等优点，因而在POCT领域中应用越来越广泛。In Vitro Diagnosis (IVD) belongs to the pharmaceutical and biological industry, which refers to taking blood, body fluids, tissues and other samples from the human body, and using in vitro testing reagents, instruments, etc. to test and verify the samples in order to prevent diseases , Diagnosis, treatment testing, late-stage observation, health evaluation, genetic disease prediction, etc. In vitro diagnosis is divided into three categories: biochemical diagnosis, immunodiagnosis and molecular diagnosis according to methodology, as well as point-of-care testing (POCT) differentiated from biochemical, immunological and molecular diagnosis. Dry chemical reaction is a type of biochemical diagnosis, which uses biochemical reagents to react with a specific substrate, and then quantitatively detects the concentration of the target through an instrument to calculate certain biochemical indicators of the human body. Traditional biochemical diagnosis needs to be tested on a large-scale biochemical analyzer, which leads to high reagent consumption and insufficient flexibility. The general dry-type biochemical POCT diagnosis method has a low test throughput, and generally only one or a few tests can be tested at a time. Samples, one or several items. Microfluidics technology (Microfluidics) can integrate basic operation units such as sample preparation, reaction, separation, and detection in biological, chemical, and medical analysis processes on the chip, automatically completing the entire analysis process, greatly improving the detection efficiency, and at the same time It has the advantages of miniaturization and automation, so it is more and more widely used in the field of POCT.
在生化检测领域中，以美国的Abaxis公司为代表，率先开发了用于生化检测的微流控芯片，国内如天津微纳芯、成都斯马特等都有类似微流控芯片开发。传统产品的芯片对全血样本的定量与分配过程，往往需要将全血的分离和血清的定量过程分开，因此需要进行多次的离心分离和定量，使得样本处理的时间比较长，导致检测时间过于延长。In the field of biochemical testing, Abaxis of the United States took the lead in the development of microfluidic chips for biochemical testing. Domestic companies such as Tianjin Micronanochip and Chengdu Smart have similar microfluidic chip development. The process of quantification and distribution of whole blood samples with traditional products often requires separation of whole blood and serum quantification. Therefore, multiple centrifugation and quantification are required, which makes the sample processing time longer and leads to detection time. Too extended.
发明内容Summary of the invention
本申请实施例提供一种能够提高样本处理效率的微流控芯片和含有该微流控芯片的体外检测装置。The embodiments of the present application provide a microfluidic chip capable of improving sample processing efficiency and an in vitro detection device containing the microfluidic chip.
一种微流控芯片，具有加样腔体、第一微流道、第二微流道、分离定量单元、第一毛细流道和第一废液腔体；所述加样腔体具有加样孔，所述加样腔体通过所述第一微流道与所述第二微流道连通；所述微流控芯片具有旋转中心，所述第二微流道环绕所述旋转中心设置；所述第一废液腔体通过所述第一毛细流道与所述第二微流道的出液端连通；所述分离定量单元有多个，各所述分离定量单元包括第三微流道、定量腔体和第二废液腔体，所述定量腔体通过所述第三微流道与所述第二微流道连通，所述第二废液腔体与所述定量腔体连通，多个所述分离定量单元在所述第二微流道的内侧绕所述第二微流道分布；所述第一毛细流道在所述第二微流道的内侧自与所述第二微流道连接后向靠近所述旋转中心的方向延伸并弯折后向远离所述旋转中心的方向延伸以与所述第一废液腔体连通；所述第三微流道自与所述第二微流道连接后向靠近所述旋转中心的方向延伸以与所述定量腔体连通；所述定量腔体与所述第三微流道的连接位置距离所述旋转中心的距离不小于所述第一毛细流道的弯折顶点位置距离所述旋转中心的距离，所述第二废液腔体较所述定量腔体远离所述旋转中心。A microfluidic chip has a sample loading cavity, a first microfluidic channel, a second microfluidic channel, a separation and quantitative unit, a first capillary channel and a first waste liquid cavity; the sample loading cavity has a A sample hole, the sample loading cavity is communicated with the second microchannel through the first microchannel; the microfluidic chip has a center of rotation, and the second microchannel is arranged around the center of rotation The first waste liquid cavity communicates with the outlet end of the second micro-channel through the first capillary channel; there are multiple separation and quantitative units, and each of the separation and quantitative units includes a third micro-channel A flow channel, a quantitative cavity and a second waste liquid cavity, the quantitative cavity is in communication with the second micro flow channel through the third micro flow channel, and the second waste liquid cavity is connected to the quantitative cavity Body is connected, a plurality of the separation and quantification units are distributed around the second micro flow channel on the inner side of the second micro flow channel; the first capillary flow channel is self-contained on the inner side of the second micro flow channel After the second micro-channel is connected, it extends in a direction close to the rotation center, and after being bent, it extends in a direction away from the rotation center to communicate with the first waste liquid cavity; the third micro-channel is from After being connected with the second micro flow channel, it extends in a direction close to the rotation center to communicate with the quantitative cavity; the connection position of the quantitative cavity and the third micro flow channel is about a distance from the rotation center The distance is not less than the distance between the bending apex position of the first capillary flow channel and the rotation center, and the second waste liquid cavity is farther from the rotation center than the quantitative cavity.
一种体外检测装置，包括上述任一实施例所述的微流控芯片和检测机构，所述检测机构与定量腔体连通，所述检测机构设置为检测所述定量腔体内的样本。An in vitro detection device includes the microfluidic chip described in any one of the above embodiments and a detection mechanism, the detection mechanism is in communication with a quantitative cavity, and the detection mechanism is configured to detect a sample in the quantitative cavity.
附图说明Description of the drawings
图1、图2和图3分别为本申请一实施例的微流控芯片的正面、反面和侧面结构示意图。Figure 1, Figure 2 and Figure 3 are schematic diagrams of the front, back, and side structures of a microfluidic chip according to an embodiment of the application, respectively.
图4-1、图4-2、图4-3、图4-4分别为图1所示微流控芯片实现样本溶液的分离与定量流程示意图，图4-3-1、图4-3-2为局部放大示意图。Figure 4-1, Figure 4-2, Figure 4-3, Figure 4-4 are schematic diagrams of the separation and quantification flow of the sample solution by the microfluidic chip shown in Figure 1, Figure 4-3-1, Figure 4-3 -2 is a partial enlarged schematic diagram.
图5-1和图5-2分别为图1所示微流控芯片的检测流程示意图，图5-1-1为局部放大示意图。Figure 5-1 and Figure 5-2 are respectively a schematic diagram of the detection process of the microfluidic chip shown in Figure 1, and Figure 5-1-1 is a partial enlarged schematic diagram.
附图标记说明：Description of reference signs:
10：微流控芯片，101：旋转中心，102：安装部，103：芯片本体，104：透明盖膜，11：加样腔体，111：加样孔，112：第一透气孔，12：第一微流道，13：第二微流道，14：分离定量单元，141：第三微流道，142：定量腔体，143：第二废液腔体，144：出液微流道，145：渗透孔，146：第六微流道，147：第七微流道，148：第二毛细流道，148a、148b和148c为第二毛细流道上的不同 位置，149：第八微流道，15：第一毛细流道，15a、15b和15c为第一毛细流道上的不同位置，16：第一废液腔体，17：第四微流道，18，第五微流道，181：第二透气孔，19：透气微流道，191：第三透气孔，20：安装槽。10: microfluidic chip, 101: center of rotation, 102: mounting part, 103: chip body, 104: transparent cover film, 11: sample cavity, 111: sample hole, 112: first vent, 12: First micro flow channel, 13: Second micro flow channel, 14: Separation and quantitative unit, 141: Third micro flow channel, 142: Quantitative cavity, 143: Second waste liquid cavity, 144: Outlet micro flow channel , 145: permeation hole, 146: sixth micro channel, 147: seventh micro channel, 148: second capillary channel, 148a, 148b and 148c are different positions on the second capillary channel, 149: eighth micro channel Flow channel, 15: the first capillary channel, 15a, 15b and 15c are different positions on the first capillary channel, 16: the first waste liquid cavity, 17: the fourth micro channel, 18, the fifth micro channel , 181: second vent, 19: ventilated micro-channel, 191: third vent, 20: installation groove.
具体实施方式Detailed ways
除非另有定义，本文所使用的所有的技术和科学术语与属于本申请的技术领域的技术人员通常理解的含义相同。本文中在本申请的说明书中所使用的术语只是为了描述具体的实施例的目的，不是旨在于限制本申请。本文所使用的术语“和/或”包括一个或多个相关的所列项目的任意的和所有的组合。Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the technical field of this application. The terminology used in the specification of the application herein is only for the purpose of describing specific embodiments, and is not intended to limit the application. The term "and/or" as used herein includes any and all combinations of one or more related listed items.
请结合图1和图2，本申请一实施例提供了一种微流控芯片10，其具有加样腔体11、第一微流道12、第二微流道13、分离定量单元14、第一毛细流道15和第一废液腔体16。1 and FIG. 2, an embodiment of the present application provides a microfluidic chip 10, which has a sample loading cavity 11, a first micro flow channel 12, a second micro flow channel 13, a separation and quantification unit 14, The first capillary flow channel 15 and the first waste liquid cavity 16.
加样腔体11具有加样孔111。样本溶液可自加样孔111加入至加样腔体11中。加样腔体11通过第一微流道12与第二微流道13连通。微流控芯片10具有旋转中心101，在转动离心时，微流控芯片10以该旋转中心101为圆心转动。第二微流道13环绕旋转中心101设置。第一废液腔体16通过第一毛细流道15与第二微流道13的出液端连通。The sample loading cavity 11 has a sample loading hole 111. The sample solution can be added into the sample adding cavity 11 from the sample adding hole 111. The sample application cavity 11 communicates with the second micro flow channel 13 through the first micro flow channel 12. The microfluidic chip 10 has a rotation center 101. When rotating and centrifuging, the microfluidic chip 10 rotates with the rotation center 101 as the center of the circle. The second micro flow channel 13 is arranged around the center of rotation 101. The first waste liquid cavity 16 communicates with the liquid outlet end of the second micro flow channel 13 through the first capillary flow channel 15.
分离定量单元14有多个。各分离定量单元14包括第三微流道141、定量腔体142和第二废液腔体143。其中，定量腔体142通过第三微流道141与第二微流道13连通，第二废液腔体143与定量腔体142连通。多个分离定量单元14在第二微流道13的内侧绕第二微流道13分布。可选地，多个分离定量单元14绕第二微流道13均匀间隔分布。There are multiple separation and quantitative units 14. Each separation and quantitative unit 14 includes a third micro flow channel 141, a quantitative cavity 142 and a second waste liquid cavity 143. Wherein, the quantitative cavity 142 communicates with the second micro channel 13 through the third micro channel 141, and the second waste liquid cavity 143 communicates with the quantitative cavity 142. The multiple separation and quantitative units 14 are distributed around the second micro flow channel 13 inside the second micro flow channel 13. Optionally, a plurality of separation and quantitative units 14 are evenly spaced and distributed around the second micro flow channel 13.
本文所述的“环绕”可成封闭环或不成封闭环，例如可以环绕呈角度大于180°的扇形。The "surround" described herein may be a closed ring or not, for example, it may be surrounded in a fan shape with an angle greater than 180°.
在本实施例中，第一毛细流道15在第二微流道13的内侧自与第二微流道13连接后向靠近旋转中心101的方向(可以是各逐渐靠近旋转中心101的方向，例如可以是但不限于朝向旋转中心101的径向)延伸并弯折后向远离旋转中心101的方向(可以是各逐渐远离旋转中心101的方向，例如可以是但不限于背离旋转中心101的径向)延伸以与第一废液腔体16连通。第三微流道141位于第 二微流道13的内侧，第三微流道141自与第二微流道13连接后向靠近旋转中心101的方向延伸以与定量腔体142连通。In this embodiment, the first capillary flow channel 15 is connected to the second micro flow channel 13 in the inner side of the second micro flow channel 13 in a direction approaching the rotation center 101 (may be a direction gradually approaching the rotation center 101, For example, it may be, but not limited to, extend and bend in a direction away from the rotation center 101 (may be each gradually away from the rotation center 101, for example, but not limited to a diameter away from the rotation center 101). It extends toward) to communicate with the first waste liquid cavity 16. The third micro flow channel 141 is located inside the second micro flow channel 13, and the third micro flow channel 141 extends in a direction close to the rotation center 101 after being connected to the second micro flow channel 13 to communicate with the quantitative cavity 142.
在本实施例中，定量腔体142与第三微流道141的连接位置距离旋转中心101的距离大于或等于第一毛细流道15的弯折顶点位置距离旋转中心101的距离，第二废液腔体143较定量腔体142远离旋转中心101。In this embodiment, the distance between the connection position of the quantitative cavity 142 and the third micro flow channel 141 from the rotation center 101 is greater than or equal to the distance between the bending apex position of the first capillary flow channel 15 and the rotation center 101, and the second waste The liquid cavity 143 is farther away from the rotation center 101 than the quantitative cavity 142.
通过设计具有上述结构的微流控芯片10，可以一次离心即可对样本溶液进行分离和定量，并将样本溶液分配至多个分离定量单元14中，一致性好，集成度高，显著提高了单次检测的通量。By designing the microfluidic chip 10 with the above-mentioned structure, the sample solution can be separated and quantified in one centrifugation, and the sample solution can be distributed to multiple separation and quantification units 14 with good consistency and high integration, which significantly improves the unit The throughput of the test.
在一个示例中，加样腔体11环绕旋转中心101设置，一端设有加样孔111，另一端与第一微流道12连接，且可选地，加样腔体11自设有加样孔111的一端向另一端逐渐变宽，以使加入的加样溶液顺利流至第一微流道12处。进一步，加样腔体11与第一微流道12连接的一端朝向远离旋转中心101的方向延伸，并在底部与第一微流道12连接，以便于离心时将样本溶液导入第一微流道12中。In one example, the sample addition cavity 11 is arranged around the center of rotation 101, one end is provided with a sample addition hole 111, and the other end is connected to the first micro flow channel 12, and optionally, the sample addition cavity 11 is provided with its own sample addition The hole 111 gradually widens from one end to the other end, so that the added sample solution can flow smoothly to the first micro-channel 12. Further, the end of the sample adding cavity 11 connected with the first micro flow channel 12 extends in a direction away from the rotation center 101, and is connected to the first micro flow channel 12 at the bottom, so that the sample solution can be introduced into the first micro flow channel during centrifugation. Road 12.
在一些实施例中，加样腔体11在与第一微流道12连接的一端还设有第一透气孔112，第一透气孔112较加样腔体11与第一微流道12的连接位置更靠近于旋转中心101。通过设置第一透气孔112，在向加样腔体11中加入样本溶液时，可以及时将气体导出，便于样本溶液的加入。In some embodiments, the sample adding cavity 11 is further provided with a first vent 112 at one end connected to the first microfluidic channel 12. The first vent 112 is larger than the one between the sample loading cavity 11 and the first microfluidic channel 12. The connection position is closer to the center of rotation 101. By providing the first vent hole 112, when the sample solution is added to the sample adding cavity 11, the gas can be led out in time to facilitate the addition of the sample solution.
在一个示例中，第二微流道13一端与第一微流道12连接，并环绕旋转中心101延伸至另一端与第一毛细流道15连接。In an example, one end of the second micro flow channel 13 is connected to the first micro flow channel 12 and extends around the center of rotation 101 to the other end to be connected to the first capillary flow channel 15.
在一个示例中，微流控芯片10还包括第四微流道17。第一毛细流道15通过第四微流道17与第二微流道13连接，第四微流道17自与第二微流道13连接后向靠近旋转中心101的方向延伸以与第一毛细流道15连接。In an example, the microfluidic chip 10 further includes a fourth microfluidic channel 17. The first capillary flow channel 15 is connected to the second micro flow channel 13 through the fourth micro flow channel 17, and the fourth micro flow channel 17 is connected to the second micro flow channel 13 and extends in a direction close to the rotation center 101 to be connected to the first micro flow channel. The capillary flow channel 15 is connected.
在一个示例中，微流控芯片10还包括第五微流道18。第五微流道18的一端与第一废液腔体16连接，另一端具有第二透气孔181。第二透气孔181较第一废液腔体16更靠近于旋转中心101。可选地，第五微流道18自与第一废液腔体16连接后向靠近旋转中心101的方向延伸。In an example, the microfluidic chip 10 further includes a fifth microfluidic channel 18. One end of the fifth microfluidic channel 18 is connected to the first waste liquid cavity 16, and the other end has a second vent 181. The second vent 181 is closer to the rotation center 101 than the first waste liquid cavity 16. Optionally, the fifth micro channel 18 extends in a direction close to the rotation center 101 after being connected to the first waste liquid cavity 16.
在图示的示例中，第一废液腔体16在第二微流道13的外侧环绕旋转中心101设置，整个第一废液腔体16的体积保证足够大，以充分容纳多余的样本溶 液。可选地，第五微流道18中与第一废液腔体16连接的一段的径向尺寸大于靠近第二透气孔181的一段的径向尺寸，以防止液体进入到第五微流道18中而堵住第五微流道18而造成透气不及时的情况。In the example shown in the figure, the first waste liquid cavity 16 is arranged around the center of rotation 101 on the outside of the second micro flow channel 13, and the volume of the entire first waste liquid cavity 16 is ensured to be large enough to fully contain the excess sample solution. . Optionally, the radial dimension of a section of the fifth micro flow channel 18 connected to the first waste liquid cavity 16 is larger than that of the section close to the second vent 181 to prevent liquid from entering the fifth micro flow channel The fifth micro-channel 18 is blocked in the middle of 18 and the ventilation is not timely.
在一个示例中，各分离定量单元14还包括第六微流道146。定量腔体142通过第六微流道146与第三微流道141连通。In an example, each separation and quantification unit 14 further includes a sixth micro flow channel 146. The quantitative cavity 142 communicates with the third micro flow channel 141 through the sixth micro flow channel 146.
第六微流道146与第三微流道141的连接位置较定量腔体142更靠近于旋转中心101。第六微流道146与第三微流道141的连接位置距离旋转中心101的距离大于或等于第一毛细流道15的弯折顶点位置距离旋转中心101的距离。The connection position of the sixth micro flow channel 146 and the third micro flow channel 141 is closer to the rotation center 101 than the quantitative cavity 142. The distance between the connection position of the sixth micro flow channel 146 and the third micro flow channel 141 from the rotation center 101 is greater than or equal to the distance between the bending apex position of the first capillary flow channel 15 and the rotation center 101.
在一些实施例中，该微流控芯片10还包括透气微流道19。透气微流道19与各定量腔体142的第六微流道146连通。透气微流道19上设有第三透气孔191。透气微流道19较第六微流道146与第三微流道141的连接位置更靠近于旋转中心101。In some embodiments, the microfluidic chip 10 further includes a gas-permeable microfluidic channel 19. The air-permeable micro flow channel 19 communicates with the sixth micro flow channel 146 of each quantitative cavity 142. A third air hole 191 is provided on the air-permeable micro flow channel 19. The air-permeable micro flow channel 19 is closer to the rotation center 101 than the connection position of the sixth micro flow channel 146 and the third micro flow channel 141.
在图示的示例中，透气微流道19呈环形在多个分离定量单元14的内侧围绕旋转中心101设置。可选地，第三透气孔191有多个，多个第三透气孔191绕透气微流道19分布。通过设置多个透气孔191，与多个分离定量单元14相配合，可以及时将各分离定量单元14中的空气排出，便于样本溶液的导入。In the example shown in the figure, the gas-permeable micro flow channel 19 is annularly arranged on the inner side of the plurality of separation and quantitative units 14 around the rotation center 101. Optionally, there are multiple third vent holes 191, and the multiple third vent holes 191 are distributed around the breathable micro-channel 19. By arranging a plurality of ventilation holes 191 to cooperate with a plurality of separation and quantitative units 14, the air in each separation and quantitative unit 14 can be discharged in time, which facilitates the introduction of the sample solution.
在图示的示例中，第六微流道146的一端与透气微流道19连接，另一端与定量腔体142连接，第三微流道141与第六微流道146的中部连接。本文所述的“中部”可以是但不限于几何意义上的中心或中点，也可以是靠近中心或中点的位置，可选是非端部位置。In the illustrated example, one end of the sixth micro flow channel 146 is connected to the gas-permeable micro flow channel 19, the other end is connected to the quantitative cavity 142, and the third micro flow channel 141 is connected to the middle of the sixth micro flow channel 146. The "middle" mentioned herein can be, but is not limited to, the center or midpoint in a geometric sense, or a position close to the center or midpoint, and optionally a non-end position.
在一个示例中，各分离定量单元14还包括第七微流道147。第二废液腔体143通过第七微流道147与定量腔体142连通。出液微流道144与第七微流道147连接。In an example, each separation and quantification unit 14 further includes a seventh micro flow channel 147. The second waste liquid cavity 143 communicates with the quantitative cavity 142 through the seventh micro flow channel 147. The liquid outlet micro channel 144 is connected to the seventh micro channel 147.
在一个示例中，分离定量单元14还包括出液微流道144。出液微流道144的一端与定量腔体142连通，另一端设有渗透孔145。通过渗透孔145可以将定量腔体142内定量的样本溶液渗出。In an example, the separation and quantification unit 14 further includes a liquid outlet microchannel 144. One end of the liquid outlet microchannel 144 communicates with the quantitative cavity 142, and the other end is provided with a permeation hole 145. The quantitative sample solution in the quantitative cavity 142 can be exuded through the penetration hole 145.
在一些实施例中，出液微流道144包括第二毛细流道148。第二毛细流道148的一端与第七微流道147连通，另一端设有渗透孔145。在该示例中，第二毛细流道148自与第七微流道147连接后向靠近旋转中心101的方向延伸并弯 折后向远离旋转中心101的方向延伸，且定量腔体142与第三微流道141的连接位置距离旋转中心101的距离大于第二毛细流道148的弯折顶点位置距离旋转中心101的距离，第一毛细流道15的弯折顶点位置距离旋转中心101的距离大于第二毛细流道148的弯折顶点位置距离旋转中心101的距离。这样，在离心的时候，将杂质分离后的样本溶液随第二毛细流道148流动，但由于离心力的作用大于毛吸力，样本溶液不会流至第二毛细流道148的弯折顶点位置，因而第二毛细流道148就可以起到阀门的作用，在样本溶液分离和定量的时候达到关闭的效果。In some embodiments, the liquid outlet microchannel 144 includes a second capillary channel 148. One end of the second capillary channel 148 communicates with the seventh micro channel 147, and the other end is provided with a permeation hole 145. In this example, the second capillary channel 148 is connected to the seventh micro channel 147 and extends in a direction close to the rotation center 101, and after bending, it extends in a direction away from the rotation center 101, and the quantitative cavity 142 and the third The distance between the connection position of the micro flow channel 141 and the rotation center 101 is greater than the distance between the bending apex position of the second capillary channel 148 and the rotation center 101, and the distance between the bending apex position of the first capillary channel 15 and the rotation center 101 is greater than The distance between the bending vertex position of the second capillary flow channel 148 and the rotation center 101. In this way, during centrifugation, the sample solution after the impurities are separated flows along the second capillary flow channel 148, but because the centrifugal force is greater than the hair suction force, the sample solution will not flow to the bending apex position of the second capillary flow channel 148. Therefore, the second capillary flow channel 148 can function as a valve and achieve a closed effect when the sample solution is separated and quantified.
在一个示例中，该出液微流道144还包括第八微流道149。第八微流道149与第七微流道147的中部连接，第二毛细流道148通过第八微流道149与第七微流道147连通。In an example, the liquid outlet microchannel 144 further includes an eighth microchannel 149. The eighth micro flow channel 149 is connected to the middle of the seventh micro flow channel 147, and the second capillary flow channel 148 communicates with the seventh micro flow channel 147 through the eighth micro flow channel 149.
该微流控芯片10的中部还设有安装部102。安装部102的中心即微流控芯片10的旋转中心101。The middle part of the microfluidic chip 10 is also provided with a mounting part 102. The center of the mounting portion 102 is the rotation center 101 of the microfluidic chip 10.
本文所述的毛细流道是比微流道尺寸(例如宽度和/或深度)更小的流道结构。在一个示例中，第一毛细流道15与第二毛细流道148呈V字形状，其折弯部分靠近于旋转中心101。可选地，第一毛细流道15与第二毛细流道148的宽度为0.1mm～0.2mm，深度为0.1mm～0.2mm；或者第一毛细流道15与第二毛细流道148的宽度为0.2mm～0.5mm，深度为0.2mm～0.5mm。当第一毛细流道15与第二毛细流道148的宽度为0.1mm～0.2mm，深度为0.1mm～0.2mm时无需进行表面处理，当第一毛细流道15与第二毛细流道148的宽度为0.2mm～0.5mm，深度为0.2mm～0.5mm时，第一毛细流道15与第二毛细流道148的流道可优选经PEG4000表面处理。可选地，第一毛细流道15与第二毛细流道148的宽度为0.2mm，深度也为0.2mm。第一毛细流道15与第二毛细流道148在样本溶液进入后，使样本溶液可以借由毛细作用流动至其另一端。可选地，第一毛细流道15和第二毛细流道148在不同的段有不同的尺寸，例如第一毛细流道15与第二毛细流道148在折弯部位的宽度为0.2mm，深度也为0.2mm，其他部位的宽度为0.5mm，深度也为0.2mm，以便于液体流动和在局部形成虹吸和毛细作用。The capillary flow channel described herein is a flow channel structure having a smaller size (e.g., width and/or depth) than the micro flow channel. In an example, the first capillary flow channel 15 and the second capillary flow channel 148 are V-shaped, and the bent portion thereof is close to the rotation center 101. Optionally, the width of the first capillary flow channel 15 and the second capillary flow channel 148 is 0.1 mm to 0.2 mm, and the depth is 0.1 mm to 0.2 mm; or the width of the first capillary flow channel 15 and the second capillary flow channel 148 It is 0.2mm～0.5mm, and the depth is 0.2mm～0.5mm. When the width of the first capillary channel 15 and the second capillary channel 148 is 0.1mm～0.2mm, and the depth is 0.1mm～0.2mm, no surface treatment is required. When the first capillary channel 15 and the second capillary channel 148 are When the width is 0.2mm-0.5mm, and the depth is 0.2mm-0.5mm, the flow channels of the first capillary flow channel 15 and the second capillary flow channel 148 may preferably be surface-treated with PEG4000. Optionally, the width of the first capillary flow channel 15 and the second capillary flow channel 148 is 0.2 mm, and the depth is also 0.2 mm. After the first capillary flow channel 15 and the second capillary flow channel 148 enter the sample solution, the sample solution can flow to the other end of the sample solution by capillary action. Optionally, the first capillary flow channel 15 and the second capillary flow channel 148 have different sizes in different sections, for example, the width of the first capillary flow channel 15 and the second capillary flow channel 148 at the bending part is 0.2 mm, The depth is also 0.2mm, the width of other parts is 0.5mm, and the depth is also 0.2mm, in order to facilitate the flow of liquid and the formation of siphon and capillary action locally.
所述PEG4000表面处理可以是但不限于将1wt％的PEG4000溶液加入到毛细流道中，自然干燥后形成。PEG4000表面处理有利于增加毛细流道的毛细作用力，并且PEG4000在反应体系中属于惰性物质，一般不会与样本和检测试剂 等起反应，因而不会影响检测结果。The PEG4000 surface treatment can be, but is not limited to, adding a 1wt% PEG4000 solution to the capillary flow channel and forming it after natural drying. PEG4000 surface treatment is beneficial to increase the capillary force of the capillary flow channel, and PEG4000 is an inert substance in the reaction system, and generally does not react with samples and detection reagents, so it will not affect the test results.
如图3所示，在一个示例中，微流控芯片10包括芯片本体103和覆盖在芯片本体103上的透明盖膜104。芯片本体103与透明盖膜104配合形成各腔体结构和流道结构。示例性的，各腔体结构和流道结构的沟槽等均预形成在芯片本体103上，如图2所示，各孔均开口在芯片本体103的背面，而各腔体结构和流道结构的沟槽则开口在芯片本体103的正面，后续通过透明盖膜104覆盖并密封在芯片本体103的正面即可形成完成对腔体结构和流道结构的封装，形成完整的腔体结构和流道结构。As shown in FIG. 3, in an example, the microfluidic chip 10 includes a chip body 103 and a transparent cover film 104 covering the chip body 103. The chip body 103 and the transparent cover film 104 cooperate to form various cavity structures and flow channel structures. Exemplarily, the grooves of each cavity structure and flow channel structure are pre-formed on the chip body 103, as shown in FIG. 2, each hole is opened on the back of the chip body 103, and each cavity structure and flow channel The groove of the structure is opened on the front surface of the chip body 103, and subsequently covered by a transparent cover film 104 and sealed on the front surface of the chip body 103 to complete the packaging of the cavity structure and the flow channel structure, forming a complete cavity structure and Runner structure.
透明盖膜104可以是但不限于透明胶带或者透明压敏胶薄膜等，其与芯片本体103配合构成整个微流控芯片10，装配简单，无需使用复杂、昂贵的超声焊接技术，直接粘接即可，可以显著降低制作成本。可理解，在其他示例中，微流控芯片10也可以采用成本较高的超声焊接技术焊接形成，或者采用3D打印技术一体成型。The transparent cover film 104 can be, but is not limited to, a transparent tape or a transparent pressure-sensitive adhesive film, etc., which cooperates with the chip body 103 to form the entire microfluidic chip 10, which is simple to assemble and does not need to use complex and expensive ultrasonic welding technology. Yes, the production cost can be significantly reduced. It can be understood that, in other examples, the microfluidic chip 10 may also be formed by welding with a relatively high-cost ultrasonic welding technology, or be integrally formed with a 3D printing technology.
本申请还提供了一种体外检测装置，其包括上述微流控芯片10和检测机构。检测机构与定量腔体142连通，例如可以通过但不限于渗透孔145与定量腔体142连通。检测机构设置为检测定量腔体142内的样本。The application also provides an in vitro detection device, which includes the above-mentioned microfluidic chip 10 and a detection mechanism. The detection mechanism communicates with the quantitative cavity 142, for example, but not limited to, communicates with the quantitative cavity 142 through the permeation hole 145. The detection mechanism is configured to detect the sample in the quantitative cavity 142.
在一个示例中，检测机构为干化学试纸。示例性的，该干化学试纸可以包括支撑层和在支撑层上依次层叠设置的反应指示层和扩散层，反应指示层中含有能够与待测样本中目标物质反应的反应试剂和指示试剂，扩散层通过进样口面向于渗透孔145。可理解，在其他示例中，检测机构也不限于干化学试纸，也可以是各类其他试纸条或者反应器等。In one example, the detection mechanism is a dry chemical test paper. Exemplarily, the dry chemical test paper may include a support layer and a reaction indicator layer and a diffusion layer sequentially stacked on the support layer. The reaction indicator layer contains a reaction reagent and an indicator reagent capable of reacting with the target substance in the sample to be tested. The layer faces the permeation hole 145 through the injection port. It can be understood that, in other examples, the detection mechanism is not limited to dry chemical test paper, and may also be various other test paper strips or reactors.
在一个示例中，如图2所示，该微流控芯片10围绕各分离定量单元14的渗透孔145设有安装槽20，检测机构镶嵌在各安装槽20中。In an example, as shown in FIG. 2, the microfluidic chip 10 is provided with installation grooves 20 around the permeation holes 145 of each separation and quantitative unit 14, and the detection mechanism is embedded in each installation groove 20.
该微流控芯片10可以通过一次离心实现对样本溶液的杂质分离和定量，如实现对全血样本的血细胞和血清(血浆)分离和血清的定量，并通过第二毛细流道148的阀门作用，实现对不同分离定量单元14的同步上样检测。因而，使用该微流控芯片10的体外检测装置可以一次上样实现对样本的不同指标检测或同一指标的重复检测。各分离定量单元14均环绕旋转中心101设置，集成度高，通过该使用该体外检测装置可以提高检测结果的一致性、准确性和可靠性。The microfluidic chip 10 can realize the separation and quantification of impurities in the sample solution by one centrifugation, such as the separation and quantification of blood cells and serum (plasma) of a whole blood sample, and the valve function of the second capillary flow channel 148 , To achieve simultaneous sample loading detection of different separation and quantification units 14. Therefore, the in vitro detection device using the microfluidic chip 10 can realize the detection of different indexes of the sample or the repeated detection of the same index by loading the sample at one time. Each separation and quantification unit 14 is arranged around the center of rotation 101 and has a high degree of integration. By using the in vitro detection device, the consistency, accuracy and reliability of the detection result can be improved.
在一些实施例中，以图1所示的微流控芯片10为例，在样本溶液的杂质分离和待测溶液定量时，流程可参考但不限于如下：In some embodiments, taking the microfluidic chip 10 shown in FIG. 1 as an example, when separating impurities in a sample solution and quantifying a solution to be tested, the process can refer to but is not limited to the following:
如图4-1所示，将一定量的样本溶液自加样孔111加入至加样腔体11中，加样腔体11中的空气可自第一透气孔112排出。加完样本溶液后，将微流控芯片10通过其安装部102安装在具有转动离心功能的仪器中，开启仪器，将微流控芯片10以不限于4000-6000rpm的转速离心转动。As shown in FIG. 4-1, a certain amount of sample solution is added into the sample adding cavity 11 from the sample adding hole 111, and the air in the sample adding cavity 11 can be discharged from the first vent hole 112. After the sample solution is added, the microfluidic chip 10 is installed in an instrument with a rotating centrifugal function through its mounting part 102, the instrument is turned on, and the microfluidic chip 10 is centrifuged at a speed not limited to 4000-6000 rpm.
如图4-2所示，在离心力的作用下，样本溶液开始流动，从加样腔体11的一端流动至另一端，并经第一微流道12进入环形的第二微流道13中。As shown in Figure 4-2, under the action of centrifugal force, the sample solution starts to flow, from one end of the sample loading chamber 11 to the other end, and enters the annular second microchannel 13 through the first microchannel 12 .
如图4-3所示，随着样本溶液的继续流入，样本溶液依次进入分离定量单元14的第三微流道141、第六微流道146、定量腔体142、第七微流道147、第二废液腔体143、第八微流道149和第二毛细流道148中，这些流道和腔体构成连通器的结构，原流道和腔体中的空气自透气微流道19的第三透气孔191排出。如图4-3-1所示，在样本溶液充满定量腔体142到达第三微流道141与第六微流道146的交界点时，同时样本溶液也通过第八微流道149进入第二毛细流道148中，并在第二毛细流道148中流动，在快速离心的作用下，离心力大于毛吸力，当样本溶液在第二毛细流道148中流至与第三微流道141与第六微流道146的连接部位齐平的位置148a处时就不再流动，由于第二毛细流道148的折弯部位148b与旋转中心101的距离较第三微流道141与第六微流道146的连接部位与旋转中心101的距离近，因此，样本溶液不会上升至第二毛细流道148的折弯部位148b，也不会在第二毛细流道148中形成虹吸效应而经过148c段后从渗透孔145流出，至此，即完成对样本溶液的定量。As shown in Figure 4-3, as the sample solution continues to flow in, the sample solution sequentially enters the third micro-channel 141, the sixth micro-channel 146, the quantitative cavity 142, and the seventh micro-channel 147 of the separation and quantitative unit 14 In the second waste liquid cavity 143, the eighth micro channel 149 and the second capillary channel 148, these channels and the cavity constitute the structure of the communicating device, and the air in the original channel and the cavity is self-permeable micro channel The third ventilation hole 191 of 19 is discharged. As shown in Figure 4-3-1, when the sample solution fills the quantitative cavity 142 to the junction of the third microchannel 141 and the sixth microchannel 146, the sample solution also enters the second through the eighth microchannel 149. In the second capillary channel 148 and flow in the second capillary channel 148, under the action of rapid centrifugation, the centrifugal force is greater than the hair suction force. When the sample solution flows in the second capillary channel 148 to the third micro channel 141 and When the connection part of the sixth micro channel 146 is flush with the position 148a, the flow is no longer. Because the distance between the bending part 148b of the second capillary channel 148 and the rotation center 101 is longer than that of the third micro channel 141 and the sixth micro channel 141 The distance between the connection part of the flow channel 146 and the rotation center 101 is close, therefore, the sample solution will not rise to the bending part 148b of the second capillary flow channel 148, nor will it cause a siphon effect in the second capillary flow channel 148 to pass through After section 148c, it flows out from the permeation hole 145. At this point, the quantification of the sample solution is completed.
如图4-3-2所示，与此同时，样本溶液通过第二微流道13、第四微流道17进入第一毛细流道15中，样本溶液通过15a段后继续前进，由于第一毛细流道15的弯折顶点部位与旋转中心101的距离跟第三微流道141与第六微流道146的连接部位与旋转中心101的距离一致，因此，样本溶液能够到达最高点15b，如图4-3所示，随着样本溶液的继续流动，第一毛细流道15被填满，在离心力的作用下，形成持续的虹吸作用，将多余的样本溶液不断排出至第一废液腔体16中，这样可以提高定量的准确性，同时避免样本溶液的交叉污染。As shown in Figure 4-3-2, at the same time, the sample solution enters the first capillary channel 15 through the second microchannel 13 and the fourth microchannel 17, and the sample solution continues to advance after passing through the 15a section. The distance between the bent apex of a capillary channel 15 and the center of rotation 101 is the same as the distance between the connection part of the third micro channel 141 and the sixth micro channel 146 and the center of rotation 101, so the sample solution can reach the highest point 15b As shown in Figure 4-3, as the sample solution continues to flow, the first capillary channel 15 is filled, and under the action of centrifugal force, a continuous siphon effect is formed, and the excess sample solution is continuously discharged to the first waste In the liquid chamber 16, this can improve the accuracy of quantification and avoid cross-contamination of the sample solution.
如图4-4所示，继续离心转动，在离心力的作用下，可以将定量腔体142中的固定杂质(如全血样本的血细胞等)与液体分离，固定杂质最终进入第二 废液腔体143中，这样就实现了样本溶液中杂质与待测溶液的分离。As shown in Figure 4-4, continue centrifugal rotation, under the action of centrifugal force, the fixed impurities (such as blood cells of a whole blood sample) in the quantitative cavity 142 can be separated from the liquid, and the fixed impurities finally enter the second waste liquid chamber In the body 143, the impurities in the sample solution and the solution to be tested are separated in this way.
该微流控芯片10在样本溶液的杂质与待测溶液的分离和待测溶液的定量过程只需要一次离心操作就可，通过第二毛细流道148的阀门作用，在样本溶液的分离和定量时，可以将样本溶液关闭在定量腔体142和第二废液腔体143中而不流出。The microfluidic chip 10 requires only one centrifugal operation in the separation of impurities in the sample solution from the solution to be tested and the quantification of the solution to be tested. The valve function of the second capillary channel 148 is used in the separation and quantification of the sample solution. At this time, the sample solution can be closed in the quantitative cavity 142 and the second waste liquid cavity 143 without flowing out.
在检测时，可参考但不限于如下流程：When testing, you can refer to but not limited to the following process:
如图5-1、图5-2和图5-1-1所示，当待测溶液定量结束后，停止离心，第二毛细流道148中的待测溶液在毛吸力的作用下，不断前进，并越过最高点148b进入第二毛细流道148的148c段，最后到达渗透孔145。此时，可以开启低速离心，如以1000-2500rpm的转速转动，在虹吸作用下，配合离心作用，定量在定量腔体142中的待测溶液不断经由渗透孔145渗出至检测机构中，进行生化反应被检测。As shown in Figure 5-1, Figure 5-2 and Figure 5-1-1, when the quantification of the solution to be tested is completed, the centrifugation is stopped, and the solution to be tested in the second capillary flow channel 148 is constantly under the action of gross suction. Go forward and pass the highest point 148b into the 148c section of the second capillary channel 148, and finally reach the permeation hole 145. At this time, you can turn on low-speed centrifugation, such as rotating at 1000-2500 rpm, under the action of siphon, and with centrifugation, the solution to be tested quantitatively in the quantitative cavity 142 continuously leaks out into the detection mechanism through the permeation hole 145 to proceed. The biochemical reaction is tested.
该微流控芯片10是通过第二毛细流道148来作为控制样本与检测机构接触反应的阀门，可以代替传统的水溶性膜或阀门等延时打开机构，使进样检测过程更加稳定可靠，同时简化了芯片组装工艺，有利于降低生产成本。The microfluidic chip 10 uses the second capillary channel 148 as a valve to control the contact reaction between the sample and the detection mechanism, which can replace the traditional water-soluble membrane or valve and other delayed opening mechanisms, making the sampling and detection process more stable and reliable. At the same time, the chip assembly process is simplified, which helps reduce production costs.
上述微流控芯片通过设计加样腔体、第一微流道、第二微流道、多个分离定量单元、第一毛细流道和第一废液腔体，其中，第一微流道、第二微流道、各分离定量单元的第三微流道和第一毛细流道等构成连通器的结构。在向加样腔体中加入样本溶液后，通过旋转离心，样本溶液经第一微流道进入第二微流道，并在第二微流道中分流分别进入各分离定量单元的第三微流道，这样样本溶液在离心作用下会进入定量腔体中，并依次将第二废液腔体和定量腔体填满，通过离心可将血细胞等固体废物离心沉积至与定量腔体连通的第二废液腔体中，实现全血等样本的分离和在定量腔体中的定量，多余的样本溶液通过第二微流道进入第一毛细流道中，由于分离定量单元中的定量腔体与第三微流道的连接位置距离微流控芯片的旋转中心的距离等于第一毛细流道的弯折顶点位置距离旋转中心的距离，这样在当样本溶液到达第一微流道的弯折顶点时会继续前进，并在离心力的作用下，形成虹吸作用，将多余的样本溶液导入第一废液腔体。The above microfluidic chip is designed by designing a sample addition cavity, a first microfluidic channel, a second microfluidic channel, a plurality of separation and quantitative units, a first capillary channel and a first waste liquid cavity, wherein the first microfluidic channel , The second micro flow channel, the third micro flow channel and the first capillary flow channel of each separation and quantitative unit constitute the structure of the communicating device. After adding the sample solution to the sample loading chamber, by rotating and centrifuging, the sample solution enters the second micro flow channel through the first micro flow channel, and splits into the third micro flow of each separation and quantification unit in the second micro flow channel. In this way, the sample solution will enter the quantitative cavity under the action of centrifugation, and fill the second waste liquid cavity and the quantitative cavity in turn. Through centrifugation, solid wastes such as blood cells can be centrifuged and deposited to the second fluid chamber connected to the quantitative cavity. In the second waste liquid chamber, the separation of whole blood and other samples and the quantification in the quantitative chamber are realized. The excess sample solution enters the first capillary flow channel through the second micro flow channel. The distance between the connection position of the third microchannel and the center of rotation of the microfluidic chip is equal to the distance between the bending apex of the first capillary channel and the center of rotation, so that when the sample solution reaches the bending apex of the first microchannel The time will continue to advance, and under the action of centrifugal force, a siphon effect is formed, and the excess sample solution is introduced into the first waste liquid chamber.
该微流控芯片在加入样本溶液后只需要一次离心就可以实现样本溶液中杂质和目标检测液的分离和定量，无需过多的离心操作，因而操作简便，需要等待的时间短，样本处理的效率显著提高。The microfluidic chip only needs one centrifugation after adding the sample solution to separate and quantify the impurities in the sample solution and the target detection solution. There is no need for excessive centrifugation, so the operation is simple, the waiting time is short, and the sample processing The efficiency is significantly improved.
该微流控芯片还设计有包括第二毛细流道的出液微流道，第二毛细流道的一端与第七微流道连通，另一端设有渗透孔，第二毛细流道自与第七微流道连接后向靠近旋转中心的方向延伸并弯折后向远离旋转中心的方向延伸，并且定量腔体与第三微流道的连接位置距离旋转中心的距离大于第二毛细流道的弯折顶点位置距离旋转中心的距离，这样在离心处理时，因离心力大于毛细管的毛吸力，样本溶液不会突破第二毛细流道的弯折位置，第二毛细流道就可以起到“阀门”的作用将样本溶液关闭在定量腔体中不流出；后续离心结束后，第二毛细流道中的液体在毛吸力的作用下，沿第二毛细流道向前运动，“阀门”开启，液体继续流动到达渗透孔后，可以自渗透孔渗出。可选的，可以配合低速离心，在虹吸作用下，液体不断自渗透孔渗出至检测机构上完成对样本的检测。The microfluidic chip is also designed with a liquid outlet microchannel including a second capillary channel. One end of the second capillary channel is connected with the seventh microchannel, and the other end is provided with a permeation hole. The second capillary channel is free from After the seventh micro-channel is connected, it extends in the direction close to the center of rotation and after bending, it extends in the direction away from the center of rotation, and the distance between the connection position of the quantitative cavity and the third micro-channel from the center of rotation is greater than that of the second capillary channel The distance between the bending apex position and the center of rotation, so that during centrifugation, because the centrifugal force is greater than the capillary suction force, the sample solution will not break through the bending position of the second capillary channel, and the second capillary channel can act as a " The function of the “valve” closes the sample solution in the quantitative chamber without flowing out; after the subsequent centrifugation, the liquid in the second capillary channel moves forward along the second capillary channel under the action of the hair suction force, and the “valve” opens. After the liquid continues to flow to the permeable hole, it can seep out from the permeable hole. Optionally, it can be combined with low-speed centrifugation, under the action of siphon, the liquid continuously seeps from the permeable hole to the detection mechanism to complete the detection of the sample.
通过第二毛细流道来作为控制样本与检测机构接触反应的阀门，可以代替传统的水溶性膜或阀门等延时打开机构，使进样检测过程更加稳定可靠，同时简化了芯片组装工艺，有利于降低生产成本。The second capillary flow channel is used as a valve to control the contact reaction between the sample and the detection mechanism, which can replace the traditional water-soluble membrane or valve and other delayed opening mechanisms, making the sampling detection process more stable and reliable, and simplifying the chip assembly process. Conducive to reducing production costs.

Claims (19)

  1. 一种微流控芯片，具有加样腔体、第一微流道、第二微流道、分离定量单元、第一毛细流道和第一废液腔体；所述加样腔体具有加样孔，所述加样腔体通过所述第一微流道与所述第二微流道连通；所述微流控芯片具有旋转中心，所述第二微流道环绕所述旋转中心设置；所述第一废液腔体通过所述第一毛细流道与所述第二微流道的出液端连通；所述分离定量单元有多个，各所述分离定量单元包括第三微流道、定量腔体和第二废液腔体，所述定量腔体通过所述第三微流道与所述第二微流道连通，所述第二废液腔体与所述定量腔体连通，多个所述分离定量单元在所述第二微流道的内侧绕所述第二微流道分布；A microfluidic chip has a sample loading cavity, a first microfluidic channel, a second microfluidic channel, a separation and quantitative unit, a first capillary channel and a first waste liquid cavity; the sample loading cavity has a A sample hole, the sample loading cavity is communicated with the second microchannel through the first microchannel; the microfluidic chip has a center of rotation, and the second microchannel is arranged around the center of rotation The first waste liquid cavity communicates with the outlet end of the second micro-channel through the first capillary channel; there are multiple separation and quantitative units, and each of the separation and quantitative units includes a third micro-channel A flow channel, a quantitative cavity and a second waste liquid cavity, the quantitative cavity is in communication with the second micro flow channel through the third micro flow channel, and the second waste liquid cavity is connected to the quantitative cavity Body connected, a plurality of the separation and quantitative units are distributed around the second micro flow channel inside the second micro flow channel;
    所述第一毛细流道在所述第二微流道的内侧自与所述第二微流道连接后向靠近所述旋转中心的方向延伸并弯折后向远离所述旋转中心的方向延伸以与所述第一废液腔体连通；所述第三微流道自与所述第二微流道连接后向靠近所述旋转中心的方向延伸以与所述定量腔体连通；The first capillary flow channel extends in a direction close to the rotation center after being connected to the second micro flow channel on the inner side of the second micro flow channel, and is bent and then extends in a direction away from the rotation center To communicate with the first waste liquid cavity; the third micro-channel extends in a direction close to the rotation center after being connected with the second micro-channel to communicate with the quantitative cavity;
    所述定量腔体与所述第三微流道的连接位置距离所述旋转中心的距离大于或等于所述第一毛细流道的弯折顶点位置距离所述旋转中心的距离，所述第二废液腔体较所述定量腔体远离所述旋转中心。The distance between the connection position of the quantitative cavity and the third micro flow channel and the rotation center is greater than or equal to the distance between the bending vertex position of the first capillary flow channel and the rotation center, and the second The waste liquid cavity is farther from the rotation center than the quantitative cavity.
  2. 如权利要求1所述的微流控芯片，其中，所述加样腔体环绕所述旋转中心设置，一端设有所述加样孔，另一端与所述第一微流道连接。The microfluidic chip of claim 1, wherein the sample loading cavity is arranged around the center of rotation, one end is provided with the sample loading hole, and the other end is connected to the first microfluidic channel.
  3. 如权利要求2所述的微流控芯片，其中，所述加样腔体在与所述第一微流道连接的一端还设有第一透气孔，所述第一透气孔较所述加样腔体与所述第一微流道的连接位置更靠近于所述旋转中心。The microfluidic chip according to claim 2, wherein the sample loading cavity is further provided with a first vent hole at one end connected to the first micro flow channel, and the first vent hole is larger than the The connection position of the sample cavity and the first micro flow channel is closer to the rotation center.
  4. 如权利要求1所述的微流控芯片，还包括第五微流道，所述第五微流道的一端与所述第一废液腔体连接，另一端具有第二透气孔，所述第二透气孔较所述第一废液腔体更靠近于所述旋转中心。The microfluidic chip according to claim 1, further comprising a fifth microfluidic channel, one end of the fifth microfluidic channel is connected to the first waste liquid cavity, and the other end has a second vent hole, the The second vent hole is closer to the rotation center than the first waste liquid cavity.
  5. 如权利要求4所述的微流控芯片，其中，所述微流控芯片满足以下至少之一：The microfluidic chip of claim 4, wherein the microfluidic chip satisfies at least one of the following:
    所述第一废液腔体在所述第二微流道的外侧环绕所述旋转中心设置；The first waste liquid cavity is arranged around the center of rotation on the outside of the second micro flow channel;
    所述第五微流道中与所述第一废液腔体连接的一段的径向尺寸大于靠近所述第二透气孔的一段的径向尺寸。The radial dimension of a section of the fifth micro flow channel connected to the first waste liquid cavity is larger than the radial dimension of a section close to the second vent hole.
  6. 如权利要求1～5中任一项所述的微流控芯片，各所述分离定量单元还包括第六微流道，所述定量腔体通过所述第六微流道与所述第三微流道连通；The microfluidic chip according to any one of claims 1 to 5, each of the separation and quantification units further comprises a sixth micro flow channel, and the quantitative cavity passes through the sixth micro flow channel and the third micro flow channel. Micro-channel connection;
    所述第六微流道与所述第三微流道的连接位置较所述定量腔体更靠近于所 述旋转中心；所述第六微流道与所述第三微流道的连接位置距离所述旋转中心的距离大于或等于所述第一毛细流道的弯折顶点位置距离所述旋转中心的距离。The connection position of the sixth micro flow channel and the third micro flow channel is closer to the rotation center than the quantitative cavity; the connection position of the sixth micro flow channel and the third micro flow channel The distance from the rotation center is greater than or equal to the distance between the bending vertex position of the first capillary flow channel and the rotation center.
  7. 如权利要求6所述的微流控芯片，还包括透气微流道，所述透气微流道与各所述定量腔体的所述第六微流道连通，所述透气微流道上设有第三透气孔；The microfluidic chip according to claim 6, further comprising a gas-permeable micro-channel, the gas-permeable micro-channel is connected with the sixth micro-channel of each of the quantitative cavities, and the gas-permeable micro-channel is provided with The third ventilation hole;
    所述透气微流道较所述第六微流道与所述第三微流道的连接位置更靠近于所述旋转中心。The gas-permeable micro-channel is closer to the rotation center than the connection position of the sixth micro-channel and the third micro-channel.
  8. 如权利要求7所述的微流控芯片，其中，所述透气微流道呈环形在多个所述分离定量单元的内侧围绕所述旋转中心设置，所述第三透气孔有多个，多个所述第三透气孔绕所述透气微流道分布。The microfluidic chip according to claim 7, wherein the gas-permeable micro-channel is arranged in a ring shape on the inner side of the plurality of separation and quantitative units around the center of rotation, and the third gas-permeable hole has a plurality of The three third air holes are distributed around the air-permeable micro-channels.
  9. 如权利要求7所述的微流控芯片，其中，所述第六微流道的一端与所述透气微流道连接，另一端与所述定量腔体连接，所述第三微流道与所述第六微流道的中部连接。The microfluidic chip of claim 7, wherein one end of the sixth microfluidic channel is connected to the gas-permeable microfluidic channel, the other end is connected to the quantitative cavity, and the third microfluidic channel is connected to the gas-permeable microfluidic channel. The middle part of the sixth micro channel is connected.
  10. 如权利要求1～5及7～9中任一项所述的微流控芯片，各所述分离定量单元还包括第七微流道，所述第二废液腔体通过所述第七微流道与所述定量腔体连通。The microfluidic chip according to any one of claims 1 to 5 and 7 to 9, each of the separation and quantification units further comprises a seventh micro flow channel, and the second waste liquid cavity passes through the seventh micro flow channel. The flow channel communicates with the quantitative cavity.
  11. 如权利要求10所述的微流控芯片，所述分离定量单元还包括出液微流道，所述出液微流道的一端与所述定量腔体连通，另一端设有渗透孔。10. The microfluidic chip according to claim 10, wherein the separation and quantification unit further comprises a liquid discharge microchannel, one end of the liquid discharge microchannel is in communication with the quantitative cavity, and the other end is provided with a permeation hole.
  12. 如权利要求11所述的微流控芯片，其中，所述出液微流道包括第二毛细流道，所述第二毛细流道的一端与所述第七微流道连通，另一端设有所述渗透孔；The microfluidic chip of claim 11, wherein the liquid outlet microchannel comprises a second capillary channel, one end of the second capillary channel is connected to the seventh microchannel, and the other end is provided With said penetration holes;
    所述第二毛细流道自与所述第七微流道连接后向靠近所述旋转中心的方向延伸并弯折后向远离所述旋转中心的方向延伸；The second capillary flow channel extends in a direction close to the rotation center after being connected with the seventh micro flow channel, and is bent and then extends in a direction away from the rotation center;
    所述定量腔体与所述第三微流道的连接位置距离所述旋转中心的距离大于所述第二毛细流道的弯折顶点位置距离所述旋转中心的距离，所述第一毛细流道的弯折顶点位置距离所述旋转中心的距离大于所述第二毛细流道的弯折顶点位置距离所述旋转中心的距离。The distance between the connection position of the quantitative cavity and the third micro flow channel and the rotation center is greater than the distance between the bending apex position of the second capillary flow channel and the rotation center, and the first capillary flow The distance between the bending apex position of the channel and the rotation center is greater than the distance between the bending apex position of the second capillary flow channel and the rotation center.
  13. 如权利要求12所述的微流控芯片，所述出液微流道还包括第八微流道，所述第八微流道与所述第七微流道连接，所述第二毛细流道通过所述第八微流道与所述第七微流道连通。The microfluidic chip according to claim 12, the liquid outlet microchannel further comprises an eighth microchannel, the eighth microchannel is connected to the seventh microchannel, and the second capillary channel The channel communicates with the seventh micro channel through the eighth micro channel.
  14. 如权利要求1～5、7～9及11～13中任一项所述的微流控芯片，其中，所述微流控芯片包括芯片本体和覆盖在所述芯片本体上的透明盖膜，所述芯片本 体与所述透明盖膜配合形成所述微流控芯片的各腔体结构和流道结构。The microfluidic chip according to any one of claims 1 to 5, 7 to 9 and 11 to 13, wherein the microfluidic chip comprises a chip body and a transparent cover film covering the chip body, The chip body cooperates with the transparent cover film to form each cavity structure and flow channel structure of the microfluidic chip.
  15. 如权利要求14所述的微流控芯片，其中，所述透明盖膜为透明压敏胶薄膜。The microfluidic chip of claim 14, wherein the transparent cover film is a transparent pressure-sensitive adhesive film.
  16. 一种体外检测装置，包括如权利要求1～15中任一项所述的微流控芯片和检测机构，所述检测机构与所述定量腔体连通，所述检测机构设置为检测所述定量腔体内的样本。An in vitro detection device, comprising the microfluidic chip according to any one of claims 1-15 and a detection mechanism, wherein the detection mechanism is in communication with the quantitative cavity, and the detection mechanism is configured to detect the quantitative The sample inside the cavity.
  17. 如权利要求16所述的体外检测装置，其中，所述检测机构为干化学试纸。The in vitro testing device according to claim 16, wherein the testing mechanism is a dry chemical test paper.
  18. 如权利要求17所述的体外检测装置，其中，所述干化学试纸包括支撑层和在所述支撑层上依次层叠设置的反应指示层和扩散层，所述反应指示层中含有能够与待测样本中目标物质反应的反应试剂和指示试剂，所述扩散层通过所述进样口面向于所述渗透孔。The in vitro detection device according to claim 17, wherein the dry chemical test paper comprises a support layer and a reaction indicator layer and a diffusion layer stacked on the support layer, and the reaction indicator layer contains The reaction reagent and indicator reagent for the reaction of the target substance in the sample, the diffusion layer faces the permeation hole through the injection port.
  19. 如权利要求16～18中任一项所述的体外检测装置，其中，所述微流控芯片围绕各所述分离定量单元的渗透孔设有安装槽，所述检测机构镶嵌在各所述安装槽中。The in vitro detection device according to any one of claims 16 to 18, wherein the microfluidic chip is provided with a mounting groove around the permeation hole of each of the separation and quantitative units, and the detection mechanism is embedded in each of the mounting Slot.
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