WO2019112111A1 - Puce d'analyse de microfluides incluant un micro-injecteur et son procédé de fabrication et son procédé d'utilisation - Google Patents

Puce d'analyse de microfluides incluant un micro-injecteur et son procédé de fabrication et son procédé d'utilisation Download PDF

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WO2019112111A1
WO2019112111A1 PCT/KR2017/015151 KR2017015151W WO2019112111A1 WO 2019112111 A1 WO2019112111 A1 WO 2019112111A1 KR 2017015151 W KR2017015151 W KR 2017015151W WO 2019112111 A1 WO2019112111 A1 WO 2019112111A1
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microtubule
main channel
sample
reagent
chip
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PCT/KR2017/015151
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English (en)
Korean (ko)
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한동식
황현두
최재규
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(주)비비비
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B81—MICROSTRUCTURAL TECHNOLOGY
    • B81B—MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
    • B81B3/00—Devices comprising flexible or deformable elements, e.g. comprising elastic tongues or membranes
    • B81B3/0018—Structures acting upon the moving or flexible element for transforming energy into mechanical movement or vice versa, i.e. actuators, sensors, generators
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B81—MICROSTRUCTURAL TECHNOLOGY
    • B81B—MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
    • B81B3/00—Devices comprising flexible or deformable elements, e.g. comprising elastic tongues or membranes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01M—TESTING STATIC OR DYNAMIC BALANCE OF MACHINES OR STRUCTURES; TESTING OF STRUCTURES OR APPARATUS, NOT OTHERWISE PROVIDED FOR
    • G01M3/00—Investigating fluid-tightness of structures
    • G01M3/02—Investigating fluid-tightness of structures by using fluid or vacuum
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B81—MICROSTRUCTURAL TECHNOLOGY
    • B81B—MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
    • B81B2201/00—Specific applications of microelectromechanical systems
    • B81B2201/02—Sensors
    • B81B2201/0214—Biosensors; Chemical sensors
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B81—MICROSTRUCTURAL TECHNOLOGY
    • B81B—MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
    • B81B2201/00—Specific applications of microelectromechanical systems
    • B81B2201/05—Microfluidics

Definitions

  • the present invention relates to a microfluidic analysis chip, a method of manufacturing the microfluidic analysis chip, and a method of using the microfluidic chip, and more particularly, to a microfluidic analysis chip having improved functions and accuracy as compared with the conventional microfluidic analysis chip, will be.
  • a biochip refers to an integrated product of DNA, protein, and other biomolecules on a small substrate made of glass, silicon, or nylon.
  • DNA When the DNA is integrated, it is called a DNA chip.
  • protein When the protein is integrated, Quot;
  • the biochip can be divided into a microarray chip and a micro fluidics chip.
  • a microarray chip refers to a biochip capable of arranging thousands or tens of thousands of DNAs or proteins at regular intervals, analyzing the target substance to analyze the binding pattern.
  • the microfluidics chip is a biochip capable of analyzing the reaction with various biomolecules or sensors integrated in a chip while flowing a small amount of analyte, which is also called a lab on a chip , Advanced technologies that combine the functions of pumps, valves, reactors, extractors, separation systems, etc., which are essential for the sample preparation process of automatic analyzers used in the analysis of biochemical materials, and sensor technology.
  • the lab-on-a-chip is designed to process sample injections, pretreatment, chemical reactions, separation / analysis, etc. that go through labs to analyze chemical and biochemical materials within a few cm2 of the chip It is a microanalysis device.
  • the lab-on-a-chip technology is a combination of micro flow control technology and MEMS microfabrication technology that precisely transfers, distributes and mixes tens of microliters ( ⁇ l) of sample from a few picoliter (pl) It is a core technology.
  • Rap-on-a-chip which uses trace amounts of samples and analyzes chemical components quickly and easily, is widely used to select useful new drugs at a high speed among a large number of new drug candidates. Recently, Type of lab-on-a-chip is under research and development.
  • lab-on-a-chip In contrast to micro-array chips such as DNA chips and protein chips, lab-on-a-chip is still in the R & D stage worldwide, and commercialization is limited and small. In the case of a lab-on-a-chip, the network of microchannels is simple, and the reaction process is also being carried out at an uncomplicated stage.
  • the present invention is directed to a microfluidic chip having improved functionality and accuracy and a method of manufacturing and using the same.
  • a microfluidic analysis chip comprising: a chip housing including a chip lower plate and a chip upper plate; A micro tube for a main channel formed on a surface to which the chip lower plate and the chip upper plate are coupled and having one end connected to the outside of the chip housing; A microtubule for at least one subchannel, one end of which is connected to the side of the microtubule for the main channel and the other end of which is connected to the outside of the chip housing; And at least one injector disposed in close contact with an inner wall of the sub-channel micro-tube.
  • the injector may have a gasket attached to an end of the injector facing toward the microtubule for the main channel to prevent gas from entering from the outside.
  • the microtubes for the subchannels may be indicated on the inner wall.
  • the microfluidic analysis chip according to the present invention may further include a sealing membrane located at one end of the microtubule for the subchannel and sealing the reagent injected into the microchannel for the subchannel.
  • a fine needle may be formed on the inner surface of the microtubule for the main channel at a position corresponding to the sealing film.
  • the apparatus may further include an adjustment unit that moves at least one of the chip lower plate and the chip upper plate to adjust a distance between the lower chip plate and the chip upper plate.
  • the sealing film may be composed of a photodegradable material. And a light transmission window formed at a position corresponding to the sealing film among the inner surfaces of the microtubes for the main channel.
  • the microtubes for the subchannels and the injectors are two or more, and at least two injectors may have different lengths.
  • the microfluidic analysis chip according to the present invention may further include a pressure plate positioned at a predetermined distance from the chip top plate, the distance being adjusted with the chip top plate.
  • the injector may be made of a magnetic material.
  • the microfluidic analytical chip according to the present invention is characterized in that the microfluidic analytical chip according to the present invention is a microfluidic analytical chip based on at least one of (i) whether a sample or a reagent is reached, (ii) a flow rate of the sample or the reagent , (iii) the amount of the sample or the reagent, and (iv) the type of the sample or the reagent.
  • control unit includes a plurality of electrodes installed at both ends of a target region of the microtubes for the main channel; And a sensor for measuring an impedance between the plurality of electrodes.
  • control unit may include a magnetic field measuring sensor provided at both ends of a target region of the microtubes for the main channel.
  • control unit may include: a light source provided at one end of a target region of the microtubule for the main channel; And an optical sensor provided at the other end of the target region of the micro-tube for the main channel.
  • a micro-tube for some sub-channels of the sub-channel micro-tubes is formed with a cap or valve for shielding the micro- .
  • a method for injecting a reagent into a microfluidic chip having an injector in a sub-channel micro-tube comprising the steps of: (a) injecting an injector located inside the micro- Moving in a microtubule direction for the channel; (b) injecting the reagent into the main channel microtubule through the injection port of the main channel microtubule; And (c) moving the injector to be injected into the tail tube for the target sub-channel when the reagent is located at one end of the tail tube for the target sub-channel.
  • a method for injecting a reagent into a microfluidic chip having a chip top plate and a chip bottom plate separated by a microtubule and an injector for subchannels comprising the steps of: (a) Moving a syringe located inside the target subchannel to create a space between one end of the microtubule for the target subchannel and the syringe; (b) injecting a reagent into the space; And (c) combining the chip top plate and the chip bottom plate.
  • sealing the sealing film with the sealing film may further include sealing the sealing film with the sealing film.
  • a method of operating a microfluidic analysis chip including a sealing film and a micropipette comprising the steps of: (a) injecting a sample into a main channel microtubule through an injection port of the microtubule for the main channel; step; And (b) injecting a reagent previously injected into the sub-channel micro-tube into the micro-tube for the main channel by removing the micro-needle sealing membrane.
  • a method of operating a microfluidic analysis chip having a photolytic sealing film comprising: (a) injecting a sample into a main channel microtubule through an injection port of the microtubule; And (b) irradiating the sealing film with light to inject the reagent, which has been previously injected into the sub-channel micro-tube, into the micro-tube for the main channel.
  • a method of operating a microfluidic analysis chip in which an injector is placed in a sub-channel micro-tube comprising: (a) passing a sample through a micro- Injecting; And (b) moving the injector in the direction of the microtubule for the main channel based on a predetermined injection pattern, and injecting the injected reagent into the microtubule for the main channel.
  • a method of operating a microfluidic analysis chip including a pressure plate comprising: (a) injecting a sample into a main channel microtubule through an injection port of the microtubule; And (b) moving the pressure plate in the direction of the chip top plate to move at least one of the plurality of injectors toward the microtubule for the main channel, and injecting the injected reagent into the microtubule for the main channel .
  • a method of operating a microfluidic analysis chip in which an injector is a magnetic substance comprising: (a) injecting a sample into a main channel microtubule through an injection port of the microtubule; And (b) a magnet having a polarity opposite to that of the magnetic material possessed by the injector at the bottom of the chip housing, moving the injector in the direction of the microchannel for the main channel, and transferring the injected reagent to the microchannel for the main channel And injecting.
  • a method of sampling a sub-channel micro-tube using a microfluidic chip having an injector in a sub-channel micro-tube comprising the steps of: (a) Moving the injector located in the main channel toward the microtubule for the main channel; (b) injecting the sample into the main channel microtubule through the injection port of the main channel microtubule; And (c) extracting the sample by moving the injector moved in the step (a) in the opposite direction. Furthermore, (d) washing the microtubule for the main channel when the extraction of the sample is completed.
  • a method for sampling a sub-channel micro-tube using a microfluidic analysis chip, which is a magnetic material, with an injector comprising the steps of: (a) Generating magnetism having an opposite polarity; (b) injecting the sample through the injection port of the microtubule for the main channel into the microtubule for the main channel; And (c) generating magnetism having the same polarity as the magnetic material possessed by the injector at the bottom of the chip housing, and extracting the sample.
  • a method of moving a sample or a reagent in a desired direction to a microtubule for a main channel using a microfluidic analysis chip having a cap or a valve and an injector comprising the steps of: (a) CLAIMS What is claimed is: And (b) moving the injector provided in a direction to move the sample or the reagent based on the position of the sample or reagent to move the sample or the reagent.
  • a method of moving a sample or a visual field in a desired direction to a microtubule for a main channel using a microfluidic analysis chip having a cap or a valve and an injector comprising the steps of: (a) Opening a cap provided in a direction in which the cap is moved with respect to the position; And (b) moving the injector provided in a direction opposite to the direction in which the sample or the reagent is to be moved based on the position of the sample or reagent to move the sample or the reagent.
  • a sample can be injected at a desired position.
  • the injector allows precise mixing of the sample and the reagent. This results in more reliable test results.
  • a sample can be injected by a desired amount at a desired position, it is easy to manufacture and the manufacturing cost is reduced.
  • FIG. 1 is a flowchart illustrating a method of manufacturing a microfluidic analysis chip according to an embodiment of the present invention.
  • FIG. 2 is a plan view and a cross-sectional view of a microfluidic analysis chip fabricated according to the microfluidic analysis chip manufacturing method of the present specification.
  • FIG 3 is an exemplary view in which a cap is formed in a microfluidic analysis chip according to the present invention.
  • FIG. 4 is an exemplary view illustrating injection of a surface treatment solution and a reactant solution according to an embodiment of the present invention.
  • FIG. 4 is an exemplary view illustrating injection of a surface treatment solution and a reactant solution according to an embodiment of the present invention.
  • FIG. 5 is an exemplary view illustrating the injection of a surface treatment solution and a reactant solution according to another embodiment of the present invention.
  • FIG. 6 is an exemplary view illustrating the injection of a surface treatment solution and a reactant solution according to another embodiment of the present invention.
  • FIG. 7 is a partially enlarged cross-sectional view of a microtubule for a main channel according to the present specification.
  • FIG. 8 is an illustration of an example of a method for removing unnecessary reactants according to the present invention.
  • FIG. 9 is an exemplary view illustrating washing the interior of the microtubule for the main channel according to an embodiment of the present invention.
  • FIG. 10 is a cross-sectional view of a microfluidic analysis chip according to an embodiment of the present invention.
  • FIG. 11 is a flowchart of a method of injecting a reagent into a sub-channel microtubule of a microfluidic analysis chip according to an embodiment of the present invention.
  • FIG. 12 is a flowchart of a method of injecting a reagent into a sub-channel microtubule of a microfluidic analysis chip according to another embodiment of the present invention.
  • FIG. 13 is a schematic diagram of a reagent injection method according to the prior art.
  • FIG. 14 is a cross-sectional view of a microfluidic analysis chip formed with a sealing film according to the present invention.
  • 15 is a method of operating a microfluidic chip according to an embodiment of the present invention.
  • 16 is a method of operating a microfluidic chip according to another embodiment of the present invention.
  • 17 is an exemplary view in which a plurality of injectors have different lengths according to one embodiment of the present disclosure
  • FIG. 18 is a reference diagram of a method of sampling a sample according to one embodiment of the present disclosure.
  • FIG. 19 is a partial enlarged view of a microfluidic analysis chip having a plurality of electrodes according to the present specification.
  • FIGS 20 and 21 are illustrations of microtubules for subchannels with valves in accordance with embodiments of the present disclosure
  • 22 is an exemplary view of moving a sample in a microtubule for a main channel using a cap and an injector according to an embodiment of the present invention
  • 23 is an exemplary view of moving a sample in a microtubule for a main channel using a cap and an injector according to another embodiment of the present invention.
  • 24 is an exemplary diagram for adjusting the spacing between two reagents according to one embodiment of the present disclosure.
  • 25 is an exemplary view showing mixing of a sample and a reagent according to an embodiment of the present invention.
  • spatially relative can be used to easily describe a correlation between an element and other elements.
  • Spatially relative terms should be understood in terms of the directions shown in the drawings, including the different directions of components at the time of use or operation. For example, when inverting an element shown in the figures, an element described as “below” or “beneath” of another element may be placed “above” another element .
  • the exemplary term “below” can include both downward and upward directions.
  • the components can also be oriented in different directions, so that spatially relative terms can be interpreted according to orientation.
  • FIG. 1 is a top view and a cross-sectional view of a microfluidic analysis chip according to an embodiment of the present invention.
  • FIG. 1 is a flowchart illustrating a method of manufacturing a microfluidic analysis chip according to an embodiment of the present invention.
  • a method for fabricating a microfluidic analysis chip includes fabricating a chip housing having a microtubule for a main channel and microtubes for a plurality of subchannels (S10) (S20) a surface treatment for immobilizing a reaction material on the surface of the microtubule; and injecting a reaction material (S30) through the microtubule for the main channel or the microtubule for the subchannel.
  • FIG. 2 is a plan view and a cross-sectional view of a microfluidic analysis chip fabricated according to the microfluidic analysis chip manufacturing method of the present specification.
  • the microfluidic analysis chip 100 may include a chip housing 110, a main channel microtubule 120, and a plurality of subchannel microtubules 130.
  • the chip housing 110 may be made of a polymer material such as plastic.
  • the microtubule 120 for the main channel is a space through which a sample such as blood, urine, etc. is injected and moved. Inside the microtubule for the main channel, a reaction chamber for reaction with a reagent, Can be formed. Both ends of the microtubule 120 for the main channel may be connected to the outside of the chip housing 110. The outside does not necessarily mean a physically spaced space with respect to the end of the housing. Since the main channel microtubule 120 has to be supplied with a sample, one end of the microtubule 120 must be connected to the outside for injecting the sample.
  • the sample injected into the main channel microtubule 120 should be moved to the opposite side to confirm the result after reacting with the reagent, and the result should be confirmed from the outside.
  • an inlet and an outlet of a microtubule 120 for a main channel are formed on a top surface of a chip housing are shown in the figure
  • the microfluidic analysis chip according to the present invention is not limited to the drawings. It is apparent that the inlet and the outlet may be formed in various forms such as an upper end, a lower end, a side, and the like of the chip housing. Therefore, in this specification, both ends of the main channel micro-tube 120 are connected to the outside of the chip housing 110, and the reaction between the sample and the reagent in the main channel micro- And it should be understood in various forms.
  • One end of the plurality of sub-channel micro-tubes 130 may be connected to the side of the main channel micro-tube 120 and the other end may be connected to the outside of the chip housing 110.
  • the side of the micro-tube for the main channel' refers to a side of the direction of movement of the fluid flowing in the micro-tube for the main channel. Therefore, it is not necessary that the microtubes for the subchannels are vertically connected to the surface of the microchannels for the main channel, and the microchannels for the subchannels are variously connected to the interior of the microchannels for the subchannels do. 2 there is shown an embodiment having two sub-channel micro-tubes 130, but the present invention is not limited to the illustrated embodiments, and the number thereof may vary according to need.
  • the chip housing 110 may be integrally formed by an injection method, or may be manufactured by a combination of a chip lower plate 111 and a chip upper plate 112. If the chip housing 110 is divided into a chip lower plate 111 and a chip upper plate 112, the step S10 may include forming a main channel micro tube 120 and a plurality of sub channel micro tubes 130 Fabricating the chip lower plate 111 and the chip top plate 112 and joining the chip lower plate 111 and the chip top plate 112. The bonding step may be performed by using at least one of a heat treatment, an ultraviolet treatment, and a chemical treatment to bond the chip lower plate 111 and the chip upper plate 112 together. In this case, the main channel microtubes 120 may be formed on a surface to which the chip lower plate 111 and the chip top plate 112 are coupled.
  • FIG 3 is an exemplary view in which a cap is formed in a microfluidic analysis chip according to the present invention.
  • the caps 140 are formed at the ends of the microtubes for the main channel and the sub-channels.
  • the cap 140 is configured to open or close the microtubule for the main channel or the sub channel when the cap is closed, and the microtubule is blocked from the outside, .
  • the step (S10) may further include forming a cap or a valve for blocking the micro-tube for the main channel or the micro-tube for the sub-channel to the micro-tube for the main channel or the sub- have. A method of using the cap 140 will be described below.
  • the first subchannel for the first subchannel and the first branch And (ii) a surface of a region between the microtubules for the second subchannel among the plurality of microchannels for subchannels and the second point where the microchannels for the main channel are connected, .
  • the step S20 includes the steps of removing both the ends of the main channel microtubes, the microtubes for the first subchannel and the second subchannel among the microtubules for the plurality of subchannels
  • the method comprising the steps of: closing an end of the microtubule for subchannels to be connected to the outside with a cap or a valve; and (i) connecting the microchannel for the first subchannel to the microchannel for the mainchannel (Ii) a surface of a region between a microtubule for the second subchannel and a second point to which the microchannel for the main channel is connected, Or injecting the surface treatment solution through the microtubes for the second subchannel.
  • the step S30 may include the step of connecting the ends of the microtubes for the main channel and the ends connected to the outside of the microtubes for the subchannels except the microtubules for the first and second subchannels, (I) a first point at which the microtubule for the first subchannel and the microtubule for the main channel are connected, and (ii) a second point at which the microchannel for the second subchannel is connected to the microchannel, Injecting a reagent solution through the microtubules for the first subchannel or the microchannel for the second subchannel to immobilize the reactive material on the surface of the region between the tubule and the second point to which the microchannel for the main channel is connected .
  • FIG. 4 is an exemplary view illustrating injection of a surface treatment solution and a reactant solution according to an embodiment of the present invention.
  • FIG. 4 is an exemplary view illustrating injection of a surface treatment solution and a reactant solution according to an embodiment of the present invention.
  • the surface treatment and the reaction material are fixed in a part of the microtubule for the main channel.
  • a point where the microtubes for the first subchannel and the microchannel for the main channel are connected to each other among the plurality of subchannels for the subchannels (Ii) a point at which the microtubule for the second subchannel and the microtubule for the main channel are connected, among the microtubules for the plurality of subchannels, will be referred to as a 'second point'.
  • the 'microtubes for the first subchannel' are subcellular microtubes corresponding to the first point and the 'microtubes for the second subchannel' are microtubules for the subchannel corresponding to the second point.
  • the cap formed in the main channel micro-tube 120 is closed, and the cap formed in the sub-channel micro-channel 130 is opened.
  • the ends of the microtubes for the main channel and the ends of the microtubes for the subchannels except for the first and second subchannel microtubes are capped. Since only the microtubes for the first and second subchannels are shown in Fig. 4, the way of blocking the microtubules for the remaining subchannels is not shown.
  • microtubules for subchannels other than the microtubules for the first and second subchannels may be formed according to various embodiments.
  • the surface treatment solution for fixing the reaction material is injected through the sub-channel micro tube 130, the surface between the first point and the second point is treated as shown in FIG. 4B.
  • the surface treatment solution may be bovine serum albumin (BSA), hydroxyethyl cellulose (HEC), methyl cellulose (MC), polyvinyl alcohol (PVA), pluronic polyol (PP) or dextransulfate
  • BSA bovine serum albumin
  • HEC hydroxyethyl cellulose
  • MC methyl cellulose
  • PVA polyvinyl alcohol
  • PP pluronic polyol
  • dextransulfate dextransulfate
  • the reactant solution may be injected through one end of the microtubule for the first subchannel and the other end of the microchannel for the second subchannel as shown in FIG. 4 (c)
  • the reaction material is fixed on the surface between the first point and the second point as shown in Fig. 4 (d).
  • the reactant may be a substance that chemically reacts with a specific substance, an antigen-antibody reaction substance, or a protein that binds to a specific component. That is, it may be various substances that react with the target substance depending on the characteristics of the substance to be sought in the sample.
  • FIG. 5 is an exemplary view illustrating the injection of a surface treatment solution and a reactant solution according to another embodiment of the present invention.
  • Figures 5 (a) and 5 (b) are the same as Figures 4 (a) and 4 (b). Therefore, the description of the repeated portions will be omitted and the difference will be described from the portion (c) of FIG.
  • the cap formed in the main channel micro-tube 120 is opened and the cap formed in the sub-channel micro-channel 130 is closed.
  • the reactant solution may be injected through one of the opposite ends of the main channel micro tube 120.
  • the reactive substance-fixing substance is surface-treated only between the first point and the second point, the reactive substance is fixed to the surface between the first point and the second point as shown in FIG. 5 (d).
  • FIG. 6 is an exemplary view illustrating the injection of a surface treatment solution and a reactant solution according to another embodiment of the present invention.
  • the cap formed in the main channel micro-tube 120 is opened and the cap formed in the sub-channel micro-tube 130 is closed.
  • the surface treatment solution for immobilizing the reaction material is injected through the main channel microtubes 120, as shown in FIG. 6 (b)
  • the surfaces of all the areas of the microtubules for the main channel are surface- Processing.
  • FIG. 6 (c) it is found that the cap formed in the micro-tube 120 for the main channel is closed and the cap formed in the sub-channel micro-tube 130 is opened.
  • the reactant solution may be injected through one end of the microtubule for the first sub-channel and the other end of the microtubule for the second sub-channel. As a result, the reaction material is fixed on the surface between the first point and the second point as shown in Fig. 6 (d).
  • the reactant can be fixed beyond the required first point or second point and is likely to remain on the surface of the microtubes for the subchannels.
  • FIG. 7 is a partially enlarged cross-sectional view of a microtubule for a main channel according to the present specification.
  • the microtubule for the main channel is blocked with a cap or a valve, and the surface treatment solution and the reactant solution are injected through the sub-channel microtubes corresponding to the desired local region.
  • the surface treatment solution or the reactant solution may deviate from the first point or the second point that is expected.
  • the left side is expressed as a region in which the reaction material is not fixed. Further, a part of the reactive material remained on the surface of the microtubes for the first sub-channel.
  • the manufacturing method according to the present invention is capable of removing the reactants in the undesired regions.
  • FIG. 8 is an illustration of an example of a method for removing unnecessary reactants according to the present invention.
  • the protein is immobilized between the first point and the second point according to the method of FIG. At this time, it is assumed that unwanted reactive substances are to be removed on the surface of the microchannel for the first subchannel, the surface of the microchannel for the second subchannel, the left side of the first point and the right side of the second point.
  • the left end of the microtubule for the main channel and the cap of the microtubule for the first sub-channel are opened, and the right end of the microtubule for the main channel and the microtubule for the second sub- The cap closes. Then, the remover is injected through the left end of the micro-tube for the main channel or the micro-tube for the first sub-channel.
  • FIG. 8 shows an embodiment in which microtubules for two subchannels are provided, and thus an example in which microtubules for a main channel are used together is shown.
  • the microtubes for the adjacent subchannels can perform the role of the microchannels for the main channel.
  • the microtubes for the four subchannels are provided, and the points of the microtubes for the main channel corresponding to the microtubes for the respective subchannels are referred to as the first point, the second point, the third point, and the fourth point I will name it.
  • the reaction material is fixed between the second point and the third point and the unnecessary reaction material is removed in the remaining part.
  • the microtubes for the first subchannel and the second subchannel are opened and the remaining microchannels are closed, and the remover is injected through the microchannel for the first subchannel or the microchannel for the second subchannel.
  • the third subchannel microtubule and the fourth subchannel microchannel are opened and the remaining microchannels are closed, and the remover is injected through the microchannel for the third subchannel or the microchannel for the fourth subchannel. In this way, unnecessary reaction materials will be removed from the remaining region except for the reactive substance fixed between the second point and the third point.
  • a cap or valve of the microtubule for the first or second subchannel and (ii) a cap or valve for the main channel for the main channel adjacent to the cap or valve selected in (i) And opening the valve.
  • 15 g glycine, 1 g SDS, 10 ml Tween 20, Adjust pH to 2.2, Bring volume up to 1 L, and the like are selected according to the method of bonding the surface to be removed with the substance to be removed.
  • ultrapure water solution or 20 ml SDS 10%, 12.5 ml Tris HCl pH 6.8 0.5 M, 67.5 ml ultra pure water, 0.8 ml ß-mercaptoethanol solution can be used.
  • the sample reacts with (or binds to) the reactant, but a sample that does not react with the reactant or an amount exceeding the amount of the reactant may remain in the microtubule for the main channel. Therefore, there is a need to clean the microtubes for the main channel.
  • FIG. 9 is an exemplary view illustrating washing the interior of the microtubule for the main channel according to an embodiment of the present invention.
  • the sample is injected first.
  • the sample was expressed as containing a substance that binds to the reactant.
  • FIG. 9 (b) it can be seen that the sample reacted with the reactant, but a part of the sample remained in the microtubule for the main channel.
  • the cap or valve connected to both ends of the micro-tube for the main channel is opened, (ii) the end connected to the outside of the micro- Or valve.
  • a washing liquid for washing the sample remaining in the main channel micro-tube without reacting with the reactive material through either end of the micro-tube for the main channel is injected.
  • the residual material can be removed through the washing liquid.
  • the washing solution may be variously selected according to the use environment conditions of the micro channel for the main channel and may be DIW (deionized water), PBS (phosphate buffered saline) or TBS (tris buffered saline) .
  • the hydrogel may be fixed between the first point and the second point.
  • the first subchannels for the first subchannel and the first branch And (ii) the hydration gel 160 may be fixed on the surface of a region between the microtubules for the second subchannel among the microtubules for the plurality of subchannels and the second point where the microchannels for the main channel are connected. At this time, it may further comprise a surface treatment for fixing the hydrogel on the surface of the microtubule for the main channel.
  • the above-mentioned 'hydrogel' is a polymer material and is widely used in diapers, contact lenses, medical electrodes, cell cultures, and is used for molding materials, soil moisture storage, and wound scarring for special purposes.
  • This is a hydrophilic polymer crosslinked by a cohesive force such as covalent bond, hydrogen bond, van der waals bond or physical bond, and has a three-dimensional polymer network structure capable of swelling a large amount of water in an aqueous solution Lt; / RTI >
  • Matrigel, Puramatrix, Collagen, or the like are used to form a concentration gradient of the chemical by cultivating the cells in three dimensions or through diffusion of a specific chemical through the three- Fibrin gel, PEGDA, and alginate.
  • the hydrated gel formed by ionic cross-linking method has alginate (Ca2 + ion added together), UV curable gel (photo-polymerization required) contains PEGDA And temperature sensitive gels such as collagen and matrigel. Since the kind of the hydrated gel is well known to those skilled in the art, a detailed description thereof will be omitted.
  • the hydrogel may be the reactant itself according to the present invention, or may be an agent containing the reactant according to the present invention. Also, after the reaction material according to the present invention is fixed to the surface of the microtubule for the main channel, the microtubule for the main channel may be filled by injecting the hydrogel.
  • the chip top plate and the chip housing are coupled to each other in advance, compared with the conventional manufacturing method, before the reaction material used as a reagent is fixed to the surface of the microchannel for main channel, And the bottom plate of the chip are joined first. Since the microtubule for the main channel of the microfluidic chip is very small, if the reactive substance is a protein, the protein is first fixed on the surface of the microtubule, and then the chip top plate and the chip bottom plate are bonded. At this time, since the heat treatment, the ultraviolet ray treatment and the chemical treatment are used in the process of bonding the chip top plate and the bottom plate, deformation of the protein may occur.
  • Protein structure denaturation may cause degradation of analytical performance, so it has been restricted for use in microfluidic analysis chips depending on the nature of the protein.
  • the microfluidic analysis chip 100 according to the present invention since the chip upper plate 112 and the chip lower plate 111 are first bonded to each other, and then the protein is fixed on the surface of the microtubule for the main channel, The probability of occurrence is very low.
  • FIG. 10 is a cross-sectional view of a microfluidic analysis chip according to an embodiment of the present invention.
  • the microfluidic analysis chip 100 may include a chip housing 110, a microchannel 120 for a main channel, a microchannel 130 for a subchannel, and an injector 140 have.
  • the chip housing 110 serves to enclose the main channel micro tube 120.
  • the chip housing 110 may be made of a polymer material such as plastic.
  • the chip housing 110 may be manufactured by separately manufacturing the chip upper plate and the chip lower plate, or may be fabricated at one time like a plastic injection molding method. If desired, the chip housing 110 may include a chip bottom plate 111 and a chip top plate 112.
  • the main channel microtubule 120 provides a space for reacting with the reagent while the sample injected from the sample injection port 121 formed at one end moves to the other end.
  • the main channel microtubes 120 may be formed on a surface to which the chip lower plate 111 and the chip top plate 112 are coupled.
  • the microtubule 120 for the main channel is a space through which a sample such as blood, urine, etc. is injected and moved.
  • the reaction chamber may have a relatively large diameter as compared with other spaces in the microtubules for the main channel, thereby forming a reaction chamber which is a space in which the sample and the reagent react.
  • One end of the micro tube 120 for the main channel may be connected to the outside of the chip housing 110.
  • the other end of the micro tube 120 for the main channel may be connected to the outside of the chip housing 110.
  • the outside does not necessarily mean a physically spaced space with respect to the housing. Since the main channel microtubule 120 has to be supplied with a sample, one end of the microtubule 120 must be connected to the outside for injecting the sample. After the sample loaded into the main channel microtubule 120 reacts with the reagent, it must move to the opposite side to check the result, and the result should be confirmed from the outside.
  • the microfluidic analysis chip is not limited to the drawings. It is apparent that the inlet and the outlet may be formed in various forms such as an upper end, a lower end, a side, and the like of the chip housing. Therefore, in this specification, both ends of the main channel micro-tube 120 are connected to the outside of the chip housing 110, and the reaction between the sample and the reagent in the main channel micro- And it should be understood in various forms.
  • the microfluidic analysis chip 100 may include at least one microtubule 130 for a subchannel.
  • FIG. 10 shows an embodiment having three sub-channel micro-tubes 130, the present invention is not limited to the embodiments shown in the drawings.
  • the injector 140 may be positioned close to the inner wall of the sub-channel micro-tube 130.
  • the example shown in Fig. 10 shows an embodiment in which the injectors are located in all three sub-channels for microtubes. However, the injector is not necessarily located in the microtubes for all the sub-channels. If necessary, the injector may not be located in the microtubes for some subchannels.
  • the injector 140 may have a gasket attached to an end of the injector 140 facing the microtubule for the main channel to prevent gas from entering from the outside.
  • the sucker may be made of a rubber or a polymer material, and may be a material that fills the joint between the inner wall of the sub-channel micro-tube 130 and the injector 140.
  • the injector 140 injects the substance contained in the sub-channel micro-tube 130 into the main channel micro-tube 120 or injects the substance in the main channel micro- And may be sucked into the microtubule 130 for use. In other words, the injector 140 may serve as a syringe.
  • the body of the injector 140 may be made of rigid plastic or metal material. Further, for convenience of the user, the micro tube 130 for the sub-channel may be shown with a scale on the inner wall.
  • the method of injecting a reagent into a microfluidic analysis chip including an injector according to the present invention can be roughly classified into a method of injecting a mixture before a chip upper plate and a bottom plate of a chip are combined,
  • FIG. 11 is a flowchart of a method of injecting a reagent into a sub-channel microtubule of a microfluidic analysis chip according to an embodiment of the present invention.
  • the injector located inside the microtubule for the target subchannel may be moved toward the main channel microtubule.
  • the 'micro tube for the target subchannel' means a micro tube for the subchannel to which the reagent is injected.
  • the reagent may be injected into the main channel microtubule 120 through the injection port of the main channel microtubule 120. At this point, the reagent will flow to the opposite side of the injection port for the main channel micro-tube 120 and will reach below the micro-tube for the target sub-channel.
  • the moved injector may be moved to inject the reagent into the target sub-channel micro-tube 130.
  • the injector can be moved by the amount of reagent desired.
  • the method of injecting the reagent into the microchannel for subchannel of the microfluidic chip described above with reference to FIG. 10 is similar to the process of sucking the reagent into the injector. This is similar to the process of pushing the plunger of the syringe to the end and then drawing the reagent into the syringe.
  • FIG. 12 is a flowchart of a method of injecting a reagent into a sub-channel microtubule of a microfluidic analysis chip according to another embodiment of the present invention.
  • step S20 the injectors located in the target sub-channel micro-tubes among the plurality of sub-channel micro-tubes 130 are moved, and the other end of the micro- Can be generated.
  • the size of the space may be varied depending on the amount of the reagent to be injected.
  • the reagent may be injected into the space.
  • the reagent injection may be performed by a desired amount using a pipette or a dispenser.
  • step S22 the chip upper plate 112 and the chip lower plate 111 can be coupled.
  • FIG. 13 is a schematic diagram of a reagent injection method according to the prior art.
  • the method of injecting the reagent into the microchannel for subchannels of the microfluidic analysis chip according to the present invention has an advantage in that an accurate amount of the reagent can be injected at a correct position as compared with the prior art.
  • the reagent injecting method of the microfluidic chip according to the present invention can inject accurate amounts of reagents at precise positions irrespective of the characteristics of the reagents even when two or more reagents are used in the experiment, There is an advantage that the injection method does not change even if the kind is changed. This not only ensures reproducible analysis results of the microfluidic chip, but also can lower the manufacturing cost compared to the prior art.
  • the microfluidic analysis chip 100 further includes a sealing film 150 positioned at one end of the microchannel 130 for sealing the subchannel and sealing the reagent injected into the microchannel for the subchannel can do.
  • FIG. 14 is a cross-sectional view of a microfluidic analysis chip formed with a sealing film according to the present invention.
  • the sealing film 150 covers one end of the sub-channel micro tube.
  • the sealing film 150 prevents the reagent from leaking during the circulation process after the microanalytical fluid chip is manufactured and prevents the reagent and the sample from reacting unexpectedly in the course of the experiment.
  • the sealing film 150 may seal one end of the microtubule for the target subchannel with the sealing film after the reagent is injected.
  • a process of sealing with a sealing film may be performed after step S12.
  • the material serving as the sealing membrane is injected through the injection port of the main channel micro-tube 120, the micro-tube is solidified at the end of the micro-tube for the sub- It can be sealed.
  • a process of sealing with a sealing film may be performed before step S21 and after step S22. In this case, the material serving as the sealing film may be directly sealed through the process of applying the sealing material to the end of the sub-channel micro tube.
  • the sealing film 150 must be able to be destroyed at a desired time (before or after the reagent is injected).
  • the microfluidic analysis chip 100 may further include a fine needle 151 formed at a position corresponding to the sealing film 150 among the inner surface of the microtubule for the main channel.
  • the microfluidic analysis chip 100 can identify the fine needle 151 formed on the inner surface of the microtubule for the main channel. It can be confirmed that the fine needle 151 has a fine needle 151 formed on the opposite side of the sub-channel fine tube 130 more accurately than the position corresponding to the sealing film 150.
  • the chip top plate 112 and the chip bottom plate 111 may be made of a polymer material having elasticity and capable of being slightly deformed by an external force. Therefore, before the experiment, the micro-needle 151 may be pushed through the sealing membrane 150 by pressing the chip housing 110 slightly. In the present specification, it is also possible to drill the sealing film after the injection of the reagent, although the example before the experiment, that is, before the injection of the reagent, is mentioned as an example.
  • the three fine needle lengths are different from each other.
  • the times at which the sealing membrane is pierced may vary according to the length of the micro needle.
  • the length of the fine needle 151 can be varied to control the time of destruction of the sealing film.
  • a method of operating a microfluidic analysis chip including a sealing membrane and a micropipette may include injecting a sample into the main channel microtubule 120 through an inlet of the main channel microtubule 120 have. Then, the micro-needle 151 removes the sealing film 150, thereby injecting the reagent injected into the sub-channel micro-tube 120 into the main channel micro-tube 120.
  • the microfluidic analysis chip 100 may be configured to move at least one of the chip lower plate 111 and the chip upper plate 112 to adjust the distance between the chip lower plate and the chip upper plate, As shown in FIG.
  • the adjustment unit serves to allow the fine needle 151 to penetrate the sealing film 150. That is, the adjustment unit can be understood as a mechanical device that provides an external force to the chip housing 110, not the user.
  • the sealing film 150 may be a photodegradable material. Since the sealing film made of the photodegradable material is decomposed when it receives light, the reagent and the sample can be reacted by irradiating light to the sealing film 150 at a desired time.
  • the light source for irradiating the sealing film with light may be present inside and outside the microfluidic chip. When the light source is located inside the microfluidic analysis chip, a light source such as an LED is provided on the inner surface of the sub-channel micro-tube 130 on the inner surface of the micro-tube for the main channel more accurately than the position corresponding to the sealing film 150. [ This location can be.
  • the microfluidic analysis chip 100 may further include a light transmission window 152 formed at a position corresponding to the sealing film 150 among the inner surface of the microtubule for the main channel.
  • the light transmitting window 152 allows the light emitted from the external light source to reach the sealing film when the light source is present outside the microfluidic analysis chip.
  • the sample can be first injected into the main channel microtubule through the injection port of the main channel microtubule 120. Then, by irradiating the sealing film 150 with light, the reagent injected into the sub-channel micro-tube can be injected into the main channel micro-tube.
  • the microfluidic analysis chip 100 according to the present invention differs from the microfluidic analysis chip according to the prior art in that the user can variously select and control the time point at which the reagent reacts with the sample. That is, in the case of the microanalyzed fluid chip according to the related art, since the reagent exists at a preset position, once the sample is injected, it is difficult for the user to participate in the selective reaction or reaction time of the reagent and the sample.
  • the microfluidic analysis chip 100 according to the present invention is capable of designing various reactions according to the user's intention through the injector 140.
  • 15 is a method of operating a microfluidic chip according to an embodiment of the present invention.
  • the sample can be injected into the main channel microtubule 120 through the injection port of the main channel microtubule 120.
  • the plurality of injectors 140 may be moved toward the main channel microtubule based on a predetermined injection pattern.
  • the reagent injected at the end of the moved injector 140 which is directed toward the micro-tube for the main channel, can be injected into the micro-tube for the main channel.
  • reagents reacting with the sample are sequentially flowed in a direction opposite to the injection port of the main channel micro tube 120.
  • 16 is a method of operating a microfluidic chip according to another embodiment of the present invention.
  • the leftmost red reagent, rightmost blue reagent, and finally middle yellow reagent from (a) to (f) are injected into the main channel microtubules at different time points.
  • the reagents reacted with the sample are flowed in the injected order in a direction opposite to the injection port of the main channel micro tube 120.
  • the embodiment shown in FIG. 15 is an example in which a plurality of injectors are simultaneously pressurized to simultaneously inject reagents.
  • the embodiment shown in FIG. 16 is an example in which a plurality of injectors are pressurized at different times to inject reagents.
  • the operation method of the microfluidic chip according to the present invention can be selectively injected, and the injection sequence can also be varied.
  • the lengths of the injectors are all the same.
  • the microtubes for the subchannels and the injectors are two or more, and at least two injectors may have different lengths of different lengths.
  • 17 is an exemplary view in which a plurality of injectors have different lengths according to one embodiment of the present disclosure
  • each injector injects the reagent contained in the microtubes for each subchannel due to the difference in length
  • the views may be different.
  • the length of the injector can be designed in advance according to the injection timing of the reagent. More specifically, the length of the injector of the sub-channel for the sub-channel containing the reagent to be injected earlier becomes relatively long, and the length of the injector of the sub-channel containing the reagent to be injected later becomes relatively short. In this case, the possibility that a user makes a mistake in controlling the injection timing may be lowered.
  • the microfluidic analysis chip 100 may further include a pressure plate 160 positioned at a predetermined distance from the chip top plate, the distance being adjustable with respect to the chip top plate.
  • the push plate 160 has an area corresponding to the entire injector or at least two injectors, and moves in the vertical direction of the injector.
  • a method of operating a microfluidic analysis chip including the pressure plate 160 may first inject a sample into the main channel microtubule through an injection port of the main channel microtubule. Next, the push plate 160 is moved in the direction of the chip top plate, at least one of the plurality of injectors is moved in the direction of the main channel micro-tube, and the micro- The reagent injected at the end of the main channel can be injected into the microtubule for the main channel.
  • all of the injectors are in a state in which a mechanical force is transmitted through a direct contact, thereby causing the injector to move.
  • the injector can not be moved only by direct contact. Using the magnetic force, the injector can be moved in a non-contact manner.
  • the injector 140 may be made of a magnetic material.
  • the injector 140 is a magnetic material, the injector can be moved by an external magnetic force.
  • a microfluidic chip having an injector as a magnetic material may inject a sample into the main channel microtubule through an inlet of the main channel microtubule 120.
  • a magnetic force having a polarity opposite to that of the magnetic material possessed by the injector 140 is generated at the bottom of the chip housing, the injector 140 is moved in the direction of the main channel for the main channel, May be injected into the micro channel for the main channel.
  • the opposite polarity may be generated through the electromagnet.
  • the operation method of the microfluidic chip according to the present invention is not limited to the reagent-sample mixing.
  • a method of sampling a sample as in the case of a syringe is also possible.
  • FIG. 18 is a reference diagram of a method of sampling a sample according to one embodiment of the present disclosure.
  • a method for sampling a sample in a microtubule for a subchannel using a microfluidic analysis chip in which an injector is placed in a microchannel for a subchannel (A) in the direction of the micro tube for the main channel.
  • the sample is injected into the main channel microtubule through the injection port of the main channel microtubule (b).
  • C) The sample can be extracted by moving the next injector in the opposite direction.
  • a method of sampling a microtubule for subchannel using a microfluidic analysis chip in which an injector is a magnetic material according to the present invention is characterized in that at the lower end of the chip housing 110, Lt; / RTI > Since the opposite polarity generates attractive force, the injector 140 moves to one end of the microtubule for the subchannel. Then, the sample is injected into the main channel microtubule through the injection port of the main channel microtubule 120. Next, magnetism having the same polarity as the magnetic material of the injector 140 is generated at the lower end of the chip housing 110. Since the same polarity generates a repulsive force, the injector 140 moves in a direction away from the main channel micro-tube 120. Through this, the sample can be extracted.
  • the microfluidic analysis chip 100 may be configured such that (i) whether a sample or a reagent is reached, (ii) whether the sample or reagent is reached, Or the reagent, (iii) the amount of the sample or the reagent, and (iv) the type of the sample or the reagent.
  • the control unit may include a plurality of electrodes provided at both ends of a target region of the micro channel for the main channel and a sensor for measuring impedance between the plurality of electrodes.
  • control unit may include a magnetic field measurement sensor provided at both ends of the target region of the microtubes for the main channel.
  • the optical unit may include a light source provided at one end of a target area of the micro-tube for the main channel and an optical sensor provided at the other end of the target area of the micro-tube for the main channel.
  • FIG. 19 is a partial enlarged view of a microfluidic analysis chip having a plurality of electrodes according to the present specification.
  • FIG. 19 it can be seen that two electrodes are provided in a part of the microtubule, and a voltage sensor for impedance measurement is connected between the two electrodes. Since the gas has an infinite impedance and the liquid has a relatively close impedance to zero, it is possible to electrically measure the arrival of the liquid on the region of interest when the liquid and the gas are injected in series, Injection information can be utilized as an accurate feedback control method. It is possible to measure the arrival of a liquid in a specific region, that is, a target region, by changing a magnetic field by adding a substance that affects a magnetic field in a sample or a reagent as well as an impedance change.
  • the microfluidic analysis chip including the control part is configured such that (i) whether the sample or reagent is reached, (ii) the flow rate of the sample or the reagent, (iii) The kind of the sample or the reagent, and the like.
  • a microtubule microfluidic analysis chip 100 for a plurality of subchannels may include capillaries or valves for blocking subchannel microtubules and the outside from microtubules for some subchannels for the subchannels .
  • the controller may control opening / closing of at least one of the cap or the valve based on any one of the measured impedance, the magnetic field, and the optical numerical value.
  • FIGS 20 and 21 are illustrations of microtubules for subchannels with valves in accordance with embodiments of the present disclosure
  • an electrode and a sensor for impedance measurement are installed in the micro-tube for the main channel in the transverse direction.
  • a valve is provided in the micro tube for the sub channel in the longitudinal direction.
  • (a) shows that the microtubule for the main channel is filled with gas, and the microtubule valve for the subchannel for injecting liquid is closed.
  • the sub-channel valve is opened to start the injection. Then, the liquid reaches between the electrodes as shown in (c).
  • the impedance between the electrodes is measured, since the impedance of the gas has been infinite but the liquid reaches and the impedance value close to zero is measured, it is possible to monitor the liquid reaching the region of interest and the flow rate.
  • (d) after the target volume of liquid is injected, the valve is closed to limit inflow.
  • a pink liquid flows through the microtubule for the main channel, and the valve of the microtubule for the subchannel is closed.
  • the microtubule valve for the subchannel is opened to start the injection.
  • the blue liquid closes the valve after infusion of the target volume to limit inflow.
  • the microfluidic analysis chip 100 having a cap or a valve and an injector according to the present invention can move the reagent or the sample in a desired direction in the microchannel for the main channel through opening / closing of the cap or valve and movement of the injector .
  • 22 is an exemplary view of moving a sample in a microtubule for a main channel using a cap and an injector according to an embodiment of the present invention
  • the injector 140 is installed in the microtubes for two subchannels, and the cap 170 is installed in the microtubes for one subchannel. Also, it can be seen that both ends of the micro tube for the main channel are provided with a cap.
  • the sample is injected through the injection port of the microtubule for the main channel.
  • the sample moves through the micro channel for the main channel. At this time, it is assumed that the sample needs to be moved backward.
  • the cap 170 installed on the sub-channel for the sub-channel located in the middle is closed, the cap 170 located in front of the sample is opened, and the injector 140 located behind the sample is pulled to move the sample back .
  • the cap installed at the injection port of the main channel can be opened, and the injector moved in the process (c) may be moved back to the original position.
  • the sample can be moved backward by pulling the injector 140 located before the sample.
  • the above procedure can be summarized as follows: a step of closing a cap provided in a direction to move the sample or reagent based on the position of the sample or reagent, and an injector installed in a direction to move the sample or reagent based on the position of the sample or reagent, And a moving step.
  • the example shown in FIG. 22 is an example of pulling the injector, that is, generating a negative pressure to move the sample or reagent. Conversely, positive pressure may be used to move the sample or reagent.
  • 23 is an exemplary view of moving a sample in a microtubule for a main channel using a cap and an injector according to another embodiment of the present invention.
  • the position of the initial injector rises up, unlike the embodiment shown in FIG. That is, to push the injector at a time when the movement is required, positive pressure is generated in the microtubule for the main channel.
  • the step of opening the cap provided in the direction to move the sample or the reagent based on the position of the sample or reagent and the step of moving the injector provided in the direction opposite to the direction in which the sample or reagent is to be moved are moved, And a moving step.
  • the spacing of the two samples or reagents may be adjusted to the microtubule for the main channel using a microfluidic chip with a cap or valve and an injector.
  • 24 is an exemplary diagram for adjusting the spacing between two reagents according to one embodiment of the present disclosure.
  • 25 is an exemplary view showing mixing of a sample and a reagent according to an embodiment of the present invention.
  • (a) shows that the sample is injected into the injection port of the micro-channel.
  • (b) it can be confirmed that the reagent in the sub-channel micro-tube is injected into the micro-channel micro-tube.
  • the reagent and the sample may be repeatedly moved in the microtubules for the main channel so as to be well mixed with each other.
  • (c) to (f) show examples in which the reagent and the sample are repeatedly moved using two injectors, it is obvious that the number of injectors, the opening of the caps, and the order of the injectors to be operated can be variously set .
  • the steps of a method or algorithm described in connection with the embodiments disclosed herein may be embodied directly in hardware, in software modules executed in hardware, or in a combination of the two.
  • the software module may be a random access memory (RAM), a read only memory (ROM), an erasable programmable ROM (EPROM), an electrically erasable programmable ROM (EEPROM), a flash memory, a hard disk, a removable disk, a CD- May reside in any form of computer readable recording medium known in the art to which this disclosure belongs.

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Abstract

La présente invention concerne une puce d'analyse de microfluides ayant une fonction et une précision améliorées par rapport à l'état de la technique, et un procédé de fabrication de celle-ci et un procédé d'utilisation de celle-ci. La puce d'analyse de microfluides selon la présente invention peut comprendre : un boîtier de puce comprenant une plaque inférieure de puce et une plaque supérieure de puce; un microtube pour un canal principal, le microtube pour le canal principal étant formé sur une surface au niveau de laquelle la plaque inférieure de puce et la plaque supérieure de puce sont couplées, et ayant une extrémité reliée à l'extérieur du boîtier de puce; au moins un microtube pour un sous-canal, le microtube pour le sous-canal ayant une extrémité reliée à la surface latérale du microtube pour le canal principal, et l'autre extrémité étant reliée à l'extérieur du boîtier de puce; et au moins un injecteur positionné en contact étroit avec la paroi interne du microtube pour le sous-canal.
PCT/KR2017/015151 2017-12-04 2017-12-20 Puce d'analyse de microfluides incluant un micro-injecteur et son procédé de fabrication et son procédé d'utilisation WO2019112111A1 (fr)

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KR20130135112A (ko) * 2012-05-30 2013-12-10 나노바이오시스 주식회사 다-채널 하향 액체 주입 장치, 이를 포함하는 핵산 추출 장치, 및 이를 이용한 핵산 추출 방법
KR20150117186A (ko) * 2014-04-09 2015-10-19 이성동 바이오센서
KR20160032917A (ko) * 2014-09-17 2016-03-25 서울대학교산학협력단 마이크로유체 칩을 이용한 나노크기의 알지네이트 하이드로겔의 제조방법
KR20170105825A (ko) * 2016-03-10 2017-09-20 삼성전자주식회사 미세 유체 소자, 및 이를 이용한 단일 세포 처리 방법

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