KR101410216B1 - A fabrication method of a thin chip replica and a microfluidic chip manufactured with the thin chip replica - Google Patents

Abstract

The present invention relates to a method of manufacturing a thin film chip replica, and a method of manufacturing a microfluidic chip using the thin film chip replica manufactured thereby. More particularly, the present invention relates to a method of manufacturing a microfluidic chip by injecting a curable polymer solution onto a microfluidic chip mold, A thin film chip replica is manufactured through application of a thin film hardening type polymer solution having a certain thickness, a curing reaction and a release process using a blade, and a flat substrate is attached to the lower and upper portions of the thin film chip replica, To a method for manufacturing a fluydick chip.
The microfluidic chip having the thin film chip replicas according to the present invention can be used in a variety of fields such as disease diagnosis, food analysis and biochemistry by analyzing specific amino acids or proteins. In addition, the microfluidic chip can be cultured in a microfluidic chip, It is possible to manipulate medical or biological experiments through a tissue cell.

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention [0001] The present invention relates to a thin film chip replica manufacturing method and a microfluidic chip fabricated using the same,

The present invention relates to a thin film chip replica manufacturing method and a microfluidic chip using the thin film chip replica manufactured by the method.

Recently, micro-fluidic chip has been actively developed for use in high-speed disease diagnosis and high-efficiency bioanalysis. In a typical laboratory environment, various types of experimental manipulations using a large number of sample solutions and reaction solutions using a variety of experimental tools were used, with chips smaller in size than a small slide glass size and having micrometer-sized structures inside The ongoing development of a lab-on-a-chip concept based on the concept of performing microfluidic chips demonstrates the wide range of applications and future possibilities of microfluidic chips. Active research and development in the field of micro-total analytical system (μTAS) using microfluidic chips can be used to quickly and efficiently analyze various types of biochemical materials through miniaturized analysis chips.

The microfluidic chip can be used for the analysis of chemical samples or biochemical samples, and it is possible to perform the culture of tissue cells in the microchambers and the drug test using the cultured tissue cells, and the two or more different microchannels It can also be used for mixing of solutions and synthesis by chemical reaction and for the production of functional materials. Particularly, since the volume of solution in microchannels and microchambers, which are the main constituents of microfluidic chips, is extremely small at the level below nanoliter, it is difficult to perform analysis using a toxic solution, Manipulation and analysis using a microfluidic chip is very useful when the volume of an analytical sample is extremely small, such as an analysis. In addition, the amount of sample solution or reaction solution required for synthesis and analysis using microfluidic chips is very small and the amount of discharged waste solution is very small, which is environmentally friendly.

Generally, a method for manufacturing a microfluidic chip includes a method of forming a micrometer-scale structure on a hard ceramic substrate such as a silicon wafer or a glass plate through an etching process, Or a soft material such as polydimethylsiloxane (PDMS), which is a flexible material, by a soft-lithography process or the like. Among them, a method of manufacturing a thin film chip replica or a microfluidic chip using a glass plate is disclosed in Korean Patent Registration No. 10-0788458. However, in the case of a microfluidic chip manufactured by using a hard material such as a silicon wafer or a glass plate, adhesion between a plate having a microstructure and a flat plate is difficult, and a minute gap is generated during the manufacturing process or use. It is easily generated and is a ceramic material, which is vulnerable to external impact.

Korean Patent Laid-Open No. 10-2011-0038201 discloses a method of manufacturing a microfluidic body having a microstructure thicker than a few millimeters by using a weak silicon rubber material such as polydimethylsiloxane (PDMS) or the like. However, in this case, the microstructure deformation due to the external force or the internal fluid pressure or gas pressure generated in the internal microstructure such as the microchannel or the microchamber, and the connection of each component of the microfluidic chip Detachment and breakage are likely to occur.

Korean Registered Patent No. 10-0788458 (December 24, 2007) Korean Patent Publication No. 10-2011-0038201 (April 14, 2011)

In order to solve the above problems, the present invention provides a method of manufacturing a thin film chip replica, which is a major constituent of a microfluidic chip, with a thin film in micrometers. Also provided is a microfluidic chip in which a plastic substrate for fixing is fixed on the upper part and the lower part and is made of transparent plastic. This provides a microfluidic chip that is durable, manufacturable in various sizes and shapes, and able to withstand external impacts and physical forces, compared to a microfluidic chip made only of one of flexible polymer materials or rigid ceramic materials have.

In order to achieve the above object, the present invention provides a manufacturing method of a thin film chip replica which can be manufactured with a constant thickness and a microfluidic chip using the same.

According to an aspect of the present invention,

a) a step of applying a curable polymer solution to a microfluidic chip mold including a sample solution inlet pattern, a reaction solution inlet pattern, a microchannel pattern, a microchamber pattern and a solution outlet pattern;

b) curing the curable polymer solution to release the replica from the microfluidic chip mold;

c) forming holes in the replica at a sample inlet, a reaction solution inlet, and a solution outlet;

To a method of manufacturing a thin film chip replica.

Another aspect of the present invention relates to a method of manufacturing a thin film chip replica, further comprising the step of adhering a flat substrate to the replica of step c).

Another aspect of the present invention is directed to a microfluidic chip comprising a thin film chip replica manufactured by the above method, wherein the microfluidic chip further comprises a fixture at the top, bottom, top, and bottom of the thin film chip replica This invention relates to a microfluidic chip, which is a prefabricated microfluidic chip.

In another aspect of the present invention,

An upper fixture including a tube fixing groove and a male screw injection tube;

A thin film chip replica positioned below the upper fixture;

A flat substrate disposed under the thin film chip replica to maintain the shape of the thin film chip replica;

A lower fixture disposed below the flat substrate and including a screw groove;

A male screw inserted into the male screw injection tube of the upper fixture and fixed by the screw groove of the lower fixture;

The present invention relates to a microfluidic chip.

Hereinafter, a method of manufacturing a thin film chip replica and a microfluidic chip using the method will be described in detail.

Firstly, the first step a) is a step of applying the cured polymer solution to the microfluidic chip mold including the sample solution inlet pattern, the reaction solution inlet pattern, the microchannel pattern, the microchamber pattern and the solution outlet pattern ).

The microfluidic chip mold used in the present invention may be fabricated using a material that can be easily mass produced using processes such as injection molding, hot embossing, casting, laser micromachining, and the like. Preferred are polyamide (PA), polybutylene terephthalate (PBT), polycarbonate (PC), polyethylene (PE), polymethylmethacrylate (PMMA) Polymers such as polyoxymethylene (POM), polypropylene (PP), polyphenylenether (PPE), polystyrene (PS), polysulfone (PSU), liquid crystal polymer , Polyetheretherketone (PEEK), polyetherimide (PEI), polylactide, polydimethylsiloxane (PDMS), cycloolefin copolymer (COC), polyethylene glycol di Acrylate (polyethyleneglycoldiacrylate) is preferably used.

The microfluidic chip mold used in the present invention can be manufactured by a micromachining process for performing operations such as sawing, cutting, and milling using micro devices, or by using silicon micro-machining or lithography using silicon itself And it is preferable to use the etching process. The etching process may be performed by depositing a thin film such as oxide or nitride on silicon, coating a photoresist, and irradiating ultraviolet rays to obtain a desired pattern.

The curable polymer solution used in the present invention can be prepared by mixing a polymer resin and a curing initiator. The curable polymer solution is preferably a silicon polymer or an acrylic polymer. The silicon polymer preferably has a structure in which the main chain is formed of polysiloxane, polysilane, polycarbosilane, polysilazane, etc., and hydrogen, ethyl, propyl , Butyl, phenyl, and the like, preferably polydimethylsiloxane (PDMS). As the acrylic polymer, it is preferable to use an acrylic polymer having a functional group such as acrylate or methacrylate.

The polymerization initiator is not limited to the kind within the range not impairing the object of the present invention, and it is preferable to use a photo-curing initiator or a thermal polymerization initiator.

The photocuring initiator is preferably added in combination with an acrylic polymer precursor (prepolymer). Preferably 2-hydroxy-2-methylpropiophenone, 2,6-di- (p-azabenzal) -4-methylcyclohexanone (2,6-di - (p-azidobenzal) -4-methylcyclohexanone, and 2,6-di- (p-azidobenzal) -4-cyclohexanone. Azide compounds, benzophenone, methyl-o-benzoylbenzoate, 4,4-bis (dimethylaminobenzophenon), 4 4,4-dichlorobenzophenon, 4-benzoyl-4'-methyldiphenylketone, dibenzylketone, 2,2'-diethoxy Butanedione-2- (o-ethoxycarbonyl) oxime (1-phenyl-1,2-butanedione) ), 1,3-diphenyl-propanedione-2- (o-ethoxycarbonyl) oxime, 1,3-diphenyl- -Propanedione-2- (o-benzyl) oxime (1-phenyl-3 3-phenyl-5-isoxazolone, 1-hydroxy-5-isoxazolone, N-phenylglycidyl, 1-hydroxycyclohexylphenylketone, 2-methyl- (4- (methylthio) phenyl) -2 -morpholino-1-propanone, 1-propanone, naphthalenesulfonylchloride, quinolinesulfonylchloride, N-phenylthioacridone, 4,4'-azobisisobutyronitrile (4,4'- '-azobisisobutyronitile, diphenyl sulfide, benzthiazoledisulfide, triphenylphosphine, camphorquinone, carbontetrabromide, tribophenylsulfone (also referred to as " tribromophenylsulfone, benzoylperoxide, dimethylmethylhydrogensiloxane, dimethoxyphenylacetone, Dicumyl peroxide, dicumyl peroxide, dicumyl peroxide and the like.

The thermosetting initiator is preferably an? -Aminoalkylphenone compound, an acylphosphine oxide compound, an oxime ester compound, a benzophenone compound having an amino group, or a benzoate compound having an amino group. Specifically, 2-methyl- [4- (methylthio) phenyl] -2-morpholinopropane-1- 2-dimethylamino-2- (4-methylbenzyl) -1- (4-methylphenyl) 4-morpholine-4-yl-phenyl) -butane-1-one, 2,4,6-trimethylbenzoylphenylphosphine oxide, bis (2,4,6-trimethylbenzoyl Bis (2,4,6-trimethylbenzoyl) -phenylphosphine oxide, bis (2,6-dimethoxybenzoyl) - (2,4,4-trimethylpentyl) -phosphine oxide , 6-dimethoxybenzoyl- (2,4,4-trimethylpentyl) -phosphineoxide, 1-phenyl-1,2-propanedion- 2- (o- ethoxycarbonyl) oxime, propanedione-2- (o-ethoxycarbonyl) oxime), 1,2-octanediol, 1- [4- (phenylthio) -2- phenyl-1,2-butadione-2- (o-methoxycarbonyl) oxime, methoxycarb onyl) oxime), 1,3-diphenylpropanetrityl-2- (o-ethoxycarbonyl) oxime, ethanone, 1- (o-acetyloxime), 4,4-bis (dimethylamino) benzophenone, p-dimethylaminobenzoic acid ethyl, , 2-ethylhexyl-p-aminobenzoate, and the like.

The dyes added to the curable polymer solution can be used regardless of the kind within the scope of not impairing the object of the present invention.

The curable polymer solution used in the present invention is preferably prepared by containing 90 to 99.9% by weight of polysiloxane-based silicone polymer or acrylic polymer and 0.1 to 10% by weight of a photocuring initiator.

In the present invention, the plastic replica is not limited to the type within which the object of the present invention can be achieved, and it is preferable to use any one of casting method, hot embossing method and injection molding method. More preferably, a casting method using a blade is preferably used since the thickness of the thin film chip replica to be manufactured can be made uniform.

It is preferable that the blade used in the casting method has a groove of a certain size in the blade portion. The shape of the blade including the groove may be a concave shape so that the thickness of the thin film chip replica can be made constant and the length of the groove can be freely adjusted according to the size of the thin film chip replica to be manufactured. The thickness of the thin film chip replicas prepared by controlling the gap between the blade and the microfluidic chip mold in the range of 100 to 3000 mu m is preferably adjusted.

The casting method preferably applies the curable polymer solution to the upper portion of the microfluidic chip mold. After the microfluidic chip mold is fixed and the blade moves in the uniaxial direction or the blade is fixed, The fluoride chip mold moves in the uniaxial direction so that the curable polymer solution can be effectively applied to the upper portion of the microfluidic chip mold.

Next, in step b), the cured polymer solution is cured to release the cured replicas from the microfluidic chip mold. The curing reaction may be carried out by applying heat or irradiating ultraviolet rays. In the case of the thermosetting reaction, the reaction is preferably carried out at a temperature of 10 to 200 ° C for 10 minutes to 70 hours. When the ultraviolet curing is performed, it is preferable to irradiate ultraviolet rays having a wavelength ranging from 200 to 400 nm for 5 seconds to 30 minutes. When the temperature is lower than 10 ° C, the curing reaction is delayed. When the temperature exceeds 200 ° C, a pyrolysis reaction occurs due to high temperature. If the heat curing reaction is less than 10 minutes, curing will not occur sufficiently, and if it exceeds 70 hours, there will be a cost problem due to a long heat treatment. When the ultraviolet curing is performed for less than 5 seconds, the curing is not sufficiently performed. When the ultraviolet curing is performed for 30 minutes or more, photolysis reaction by ultraviolet irradiation occurs. It is preferable that the thickness of the thin film chip replicas after the curing reaction is maintained to be constant so that the microfluidic chip can smoothly perform an experiment and a diagnostic function. Preferably, the thickness deviation of the thin film chip reflector is in the range of -5 탆 to 5 탆. Here, the thickness deviation means the difference between the highest point and the lowest point of the cured thin film chip replicas. (The meaning of thickness deviation is described.

When the curing reaction is completed, the cured replica is released from the microfluidic chip mold. When the thin film chip replica is made of a flexible silicon material, it is preferable to release the thin film chip replica because the thin film chip replica may be deformed during the releasing process.

The step c) is a step of forming holes in the cured replica at the sample inlet, the reaction solution inlet, and the solution outlet. The sample inlet, the reaction solution inlet, and the solution outlet may be formed at an obtuse angle, and the upper and lower portions of the thin film chip replicator may be formed with openings. Also, in the above step, a metal or plastic tube having a diameter of 50 to 5000 mu m may be used to press or a hole having a sharp blade may be used to form the hole.

The method may further include bonding the flat substrate to the thin film chip replica after the step c). The planar substrate may be formed of a plate-shaped ceramic or a polymer material. Preferably, the planar substrate is a flat substrate composed of a silica-based ceramic material such as glass, quartz or silicon dioxide, or a planar substrate made of an acrylic, urethane, .

When the thin film chip replica is adhered to the flat substrate, the thin film chip replica is adhered using the adhesive property inherent to the thin film chip replica, or the plasma, ultraviolet-ozone welding treatment is performed for 10 to 40 minutes The adhesive may be adhered to each other by a method such as laminating, heat and pressure, laser welding or ultrasonic welding.

The thin film chip replicas manufactured through the above manufacturing method may be used in the form adhered on the flat substrate, or may include a fixing frame at the upper, lower, upper, and lower portions of the thin film chip replica, A microfluidic chip can be manufactured. More preferably,

An upper fixture including a tube fixing groove and a male screw injection tube;

A thin film chip replica positioned below the upper fixture;

A flat substrate disposed under the thin film chip replica to maintain the shape of the thin film chip replica;

A lower fixture disposed below the flat substrate and including a screw groove;

A male screw inserted into the male screw injection tube of the upper fixture and fixed by the screw groove of the lower fixture;

The microfluidic chip is a prefabricated microfluidic chip.

In this case, when it is necessary to replace one or more of the constituent components of the microfluidic chip including the thin-film chip replica, the microfluidic chip assembled by manipulating the male screw is disassembled and replaced with a new constituent, And can be reused.

The upper fixture includes a fixing groove for connecting the sample injection tube to which the sample injection tube is connected, a fixing groove for connecting the reaction solution injection tube to which the reaction solution injection tube is connected, and a solution discharge tube connection groove to which the solution discharge tube is connected, And may have a structure having a plurality of male screw injection tubes. The upper fixture is preferably located on the top of the thin film chip replica bonded to the flat substrate. The upper fixture is made of a transparent material that transmits most of the light in visible light in the range of 400 to 800 nm, Is preferably made of an opaque material, and preferably made of a resin composition made of transparent, opaque or a mixture thereof.

The resin composition preferably contains one or more of a polymer resin such as polyamide, polyacryl, polymethylmethacrylate, epoxy, polystyrene, polyoxymethylene, polyethylene, polypropylene and polycarbonate, It is preferable to use a material prepared by mixing silica-based inorganic particles such as carbon black, silica, and silicon dioxide with one or two or more of the above-mentioned polymeric resins.

The fixing groove for connecting the sample injection tube, the fixing groove for connecting the inlet tube and the solution discharge tube, and the fixing groove for connecting the solution discharge tube have a function of connecting and fixing the respective tube connection parts connected from the upper side, And has a structure that passes through upper and lower portions of the upper fixture so that the experimenter easily transfers the desired reaction solution or solution to the thin chip chip replicas from the tube connection portions disposed at the upper portion.

The lower fixture may be made of a polymer resin which is the same as or different from the upper fixture. Preferably, the lower fixture is made of the resin composition, the polymer composite material or a mixture thereof, or a silica-based inorganic material such as quartz, glass, .

It is also preferable that the lower fixture has a screw groove and a flat substrate mounting groove. The screw groove has a function of receiving the male screw passed through the upper fixing frame and firmly fixing the upper fixing frame and the lower fixing frame. The flat board mounting groove is formed as a recessed groove on the upper surface of the lower fixing frame, You can set the location.

The male screw may be made of a material including a metal or a polymer resin. The male screw may be injected into the male screw hole of the upper fixture and then injected into the screw groove of the lower fixture to fix the assembly micro- Lt; / RTI >

The thin film chip replicas manufactured by the thin film chip replica manufacturing method according to the present invention and the microfluidic chips using the same are very simple to manufacture and the thickness of the thin chip chip replicas manufactured can be easily adjusted. In addition, a fixture is provided on the upper, lower, upper, and lower portions of the thin film chip replicas adhered to the flat substrate, and a tube for injecting or discharging a solution is provided to easily inject the sample or solution into the microfluidic chip, It is possible to solve the problem that the structure is deformed. In addition, the manufacturing method is simple and expensive equipment is not required, and mass production is possible at a low cost in a general work space. And can be assembled and separated, so that it is easy to combine and replace components and to manufacture variously according to the purpose of use.

1 and 2 schematically show a method of manufacturing a thin film chip replica according to an embodiment of the present invention.
FIG. 3 is a schematic view showing an assembly form of constituent components of a microfluidic chip according to the present invention. FIG.
4 is a perspective view illustrating a microfluidic chip according to an embodiment of the present invention.
Fig. 5 shows the manufacture and the embodiment of the thin film chip replicas manufactured according to the present invention.
Figure 6 shows an experiment using a microfluidic chip fabricated according to the present invention.
7 is a photograph showing a microfluidic chip according to the present invention.
Fig. 8 is a photograph showing an embodiment using a microfluidic chip.
9 is a photograph showing an embodiment of manufacturing a microfluidic chip including upper and lower fixtures according to the present invention.

Hereinafter, a method of manufacturing a thin film chip replica of the present invention and a microfluidic chip manufactured using the same will be described in detail with reference to the accompanying drawings and embodiments. The description and the examples of these drawings are for the purpose of describing the present invention more specifically, and the scope of the present invention is not limited by these descriptions and examples. In addition, the terms described below are defined in consideration of the functions of the present invention, which may vary depending on the intention or custom of the user, the operator. Therefore, definitions of these terms should be made based on the contents throughout this specification.

Manufacturing process of thin film chip replica

1 (a) and 1 (b) illustrate a process of manufacturing a thin film chip replica according to an embodiment of the present invention. FIG. 1 (a) shows a sample solution inlet pattern 12, a reaction solution inlet pattern 13, A microfluidic chip mold 10 having a microfluidic chip pattern 11 in which a microchannel pattern 14, a microchamber pattern 15 and a solution discharge port pattern 16 are formed in an embossed shape. When the mold is prepared, a concave-shaped blade 20 having blade fine grooves 21 as shown in (b) is placed on top of the microfluidic chip mold. At this time, the lower end of the groove of the blade having the fine grooves and the upper surface of the microfluidic chip mold 10 are kept at a predetermined interval.

After the placement on the blade, a curable polymer solution (30) is injected into the microfluidic chip mold near the blade having the fine gap as shown in (c). Then, the blade is applied to the top of the microfluidic chip mold by moving the blade in the direction of the opposite end from one end of the microfluidic chip mold as shown in (d) and (e). The thin film thickness of the applied curable polymer solution is determined by the distance between the lower end of the central portion of the blade fine groove and the upper surface of the microfluidic chip mold, and the lower end of the blade fine groove and the upper surface of the microfluidic chip mold The cured polymer thin film 31 having various thicknesses can be formed.

When the cured polymer thin film is prepared, the curing type polymer thin film 31 is thermally cured or irradiated with ultraviolet rays for a predetermined time as shown in (f) of FIG. At this time, the curing type polymer thin film 31 is deformed into a semi-solid and a solid depending on the extent of the curing reaction, thereby facilitating the release of the next step. FIG. 2 (g) is a diagram showing a thin film chip replica 40 formed by curing reaction of the cured polymer thin film, from the microfluidic chip mold 10.

(h) is a thin film chip replica which is completely released from the microfluidic chip mold, and a thin chip replica 40 in which a structure such as the micro chamber 41 is formed at an engraved angle is obtained.

When the mold is completed, holes are drilled in the sample inlet 42, the reaction solution inlet 43, and the solution outlet 47 of the thin film chip replica 40 as shown in (i), and finally the microchamber 44 and the microchamber 41 ) Is completed in the production of the thin film chip replica.

Prefabricated microfluidic chip with thin-film chip replicas

FIGS. 3 to 4 show a manufacturing process of an assembled microfluidic chip in which a fixing frame is provided as a structure on the top and bottom of the thin film chip replica of the present invention.

Fig. 3 shows the constituent components and constituent components of the assembled microfluidic chip 100 before assembly. The fixing groove for tube connection is composed of a fixing groove 61 for connecting the sample injection tube, a fixing groove 62 for connecting the reaction solution injection tube, and a fixing groove 63 for connection to the solution discharge tube, A thin film chip replica 40 disposed at a lower portion of the upper fixture 60; a flat substrate 50 disposed at a lower portion of the thin film chip replica; And a lower fixing frame 70 having a screw groove 71 and a flat board mounting groove 72 and a male screw 89 which is inserted into the male screw injection tube and fixed to the screw groove of the lower fixing frame.

The upper fixture has a fixing groove 61 for connecting the sample injection tube, a fixing groove 62 for connecting the reaction solution injection tube, a fixing groove 63 for connecting the solution discharge tube, and a plurality of male injection pipes 65 . In addition, the upper fixture 60 is made of a transparent and rigid plastic material that transmits most of the light in the visible light region, so that the inside of the microchannel 44 or the microchamber 41 of the microfluidic chip can be easily observed. It is possible to easily detect changes in fluorescence and color of a city.

The fixing groove 61 for connecting the sample injection tube, the fixing groove 62 for connecting the reaction solution injection tube, and the fixing groove 63 for connecting the solution discharge tube are connected to the tube connection portions 81 and 82 And 83 are connected and fixed to each other. The female threaded part has a structure in which the female threaded part is easily connected to the inner wall and penetrates the upper and lower parts, thereby allowing the solution from the respective tube connecting parts 81, To the lower part.

The lower fixture 70 is made of a flat solid ceramic, plastic, or metal material, and has the screw groove 71 having a screw groove 71 on its inner wall, so that the male screw 89 is injected and fixed .

The flat substrate mounting groove 72 is formed in the shape of a depressed groove on the upper surface of the lower fixture 70 and functions to position the flat substrate 50 such that it is seated at a specific position when the flat substrate 50 is placed .

The male screw 89 is made of a metal or plastic material and is injected into the male screw injection pipe 65 of the upper fixing frame 60 and then injected into the screw groove 71 of the lower fixing frame 70, And is used for assembling or separating the assembled microfluidic chip 100.

FIG. 4 is a perspective view showing a state in which the constituent components shown in FIG. 3 are assembled. When replacing one or more components of the assembled microfluidic chip 100 having the thin film chip replicas of the present invention, the microfluidic chip assembled by manipulating the male screw 89 is disassembled and a new component It is possible to reassemble and reuse by injecting and assembling.

Hereinafter, a process for manufacturing a thin film chip replica and a microfluidic chip including the same will be described in detail with reference to the accompanying drawings. It should be understood, however, that the invention is not limited to the disclosed embodiments, but, on the contrary, is intended to cover various modifications and equivalent arrangements included within the spirit and scope of the appended claims.

(Example 1)

A microfluidic chip was fabricated to confirm the function of the microfluidic chip having the thin film chip replicas and the manufacturing process of the thin chip chip replicas manufactured by the above method.

First, the microfluidic chip mold was prepared by mixing 96.9% by weight of a solution of polyethylene glycol diacrylate (average molecular weight 258, Sigma-Aldrich), 2-hydroxy-2-methylpropiophenone (manufactured by Sigma-Aldrich) and 0.1 wt% of a red dye (Rhodamin B, Sigma-Aldrich) were mixed to prepare a UV curable polymer solution for a microfluidic chip mold.

A small amount of the red dye added at this time was used for simply coloring the microfluidic chip mold in order to facilitate observation of the structure of the microfluidic chip mold to be produced.

A UV curable polymer solution for the microfluidic chip mold was applied on a glass plate to a thickness of 150 mu m and a photomask made of a plastic film material manufactured by Microtek Inc. having a transparent window in the form of a microfluidic chip was disposed thereon, Ultraviolet rays emitted from an ultraviolet lamp emitting ultraviolet rays having a maximum ultraviolet ray emission wavelength of 360 nm and a wavelength range of 200 to 400 nm are irradiated for 10 seconds to irradiate ultraviolet rays only to the microfluidic chip- The ultraviolet curable polymer solution for the microfluidic chip mold was selectively cured to solidify. Then, the photomask was removed, and the solution of the ultraviolet curable polymer for the microfluidic chip mold in the part not irradiated with ultraviolet light was removed to finally produce a microfluidic chip mold having a relief microfluidic chip structure. A photograph of the microfluidic chip mold thus produced is shown in Fig. 5 (a).

93% by weight of a polydimethylsiloxane (PDMS) polymer precursor solution (trade name: Sylgard 184 A, manufactured by Dow Corning) was applied to the top of a microfluidic chip mold having a 150 μm high relief microfluidic chip structure, And 7% by weight of a curing agent solution (trade name: Sylgard 184 B, Dow Corning) was applied to a thickness of 320 μm using a blade having a groove depth of 320 μm and a length of 6 cm, The curing reaction was carried out on a hot plate at 85 DEG C for 15 minutes. Thereafter, the cured polydimethylsiloxane thin film chip replica was peeled off from one end of the microfluidic chip mold as shown in FIG. 5 (a). FIG. 5 (b) shows a thin film chip replica of the present invention finally prepared by punching holes at the sample inlet, the reaction solution inlet and the solution outlet after the separation process. At this time, the thickness of the polydimethylsiloxane thin film chip replica was 320 탆, and the upper thickness of the microchannel and the microchamber portion was 170 탆. The thin film chip replicas prepared as described above were adhered to a glass flat substrate using the inherent adhesive property of the polydimethylsiloxane thin film chip replica to produce a basic microfluidic chip as shown in FIG. 3 (C).

In order to confirm the operation of the microfluidic chip having the thin film chip replicas manufactured, the red ink solution was dropped by one drop at the sample inlet and the reaction solution inlet, and the direction of movement of the ink was confirmed, as shown in FIG.

FIG. 4 (B) shows a drop of the red ink solution dropwise at the sample inlet and the reaction solution inlet. As a result of the capillary phenomenon caused by the hydrophilic surface of the flat substrate, the red ink was transferred from the sample inlet and the reaction solution inlet through the microchannel. After 10 seconds, the red ink reached the solution outlet through the microchannel and the micro chamber, which is shown in Fig. 4 (d). It was confirmed that the microfluidic chip prepared by the method of the present invention has a sufficient function as in the above embodiment.

(Example 2)

A microfluidic chip was prepared to confirm the function of the assembled microfluidic chip by the method of the present invention. First, a manufacturing method and a procedure of a thin film chip replica for a prefabricated microfluidic chip were fabricated in the same manner as in Example 1, and the thin film chip replica was bonded to a flat substrate at the bottom.

The upper and lower fixtures were manufactured by milling using an acrylic transparent plastic plate in order to provide a fixture on top and bottom of the thin film chip replica. Then, a male screw was used to inject into the male thread injection tube of the upper fixture to fix the upper fixture and the lower fixture to fabricate the assembled microfluidic chip. 7 and 9 show the connection of the sample injection tube and the solution discharge tube to the manufactured assembled microfluidic chip.

The fabricated microfluidic chip was injected with red ink through the sample injection tube using the same red ink as in Example 1 to confirm the movement direction of the ink, which is shown in FIG.

As shown in FIG. 8 (B), red ink injected through the sample injection tube was transferred to the microchannel and the microchamber. This is shown in Fig. 8 (C) and (D). The assembled microfluidic chip having the thin film chip replicas of the present invention has a sufficient function as a general microfluidic chip as in the case of the second embodiment as shown in FIG. I could. Particularly, since the upper plastic substrate is hard and transparent, a clear color of the red ink can be observed. As a result, the assembled microfluidic chip having the thin film chip replica of the present invention can be used for color change Fluorescence emission and the like can be detected.

Although the preferred embodiments of the present invention have been described, the present invention is not limited to the specific embodiments described above. It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the spirit or scope of the appended claims. And equivalents should also be considered to be within the scope of the present invention.

10: Microfluidic chip mold
11: Microfluidic chip pattern
12: sample solution inlet pattern
13: Reaction solution inlet pattern
14: Microchannel pattern
15: Micro chamber pattern
16: Solution outlet pattern
20: concave blade
21: blade fine groove
30: Curable polymer solution
31: Curable polymer thin film
40: thin film chip replica
41: Micro chamber
42: Sample inlet
43: reaction solution inlet
44: Microchannel
47: solution outlet
50: plane substrate
60: Upper fixture
61: Fixing groove for connecting the sample injection tube
62: Fixing groove for connecting the reaction solution injection tube
63: Fixing groove for connecting solution discharge tube
65: Male thread injection tube
70: Lower fixture
71: screw groove
72: flat substrate seating groove
81: Sample injection tube connection
82: Reaction solution injection tube connection
83: solution outlet tube connection
85: sample injection tube
86: Reaction solution injection tube
87: solution discharge tube
89: Male thread
100: Prefabricated microfluidic chip

Claims (16)

a) a replicating step of using a mixture of a polymer resin and a curing initiator in a microfluidic chip mold including a sample solution inlet pattern, a reaction solution inlet pattern, a microchannel pattern, a microchamber pattern and a solution outlet pattern;
b) curing the mixture to release the replica from the microfluidic chip mold;
c) forming holes in the replica at a sample inlet, a reaction solution inlet, and a solution outlet;
Wherein the thin film chip replica is manufactured by a method comprising the steps of: The method according to claim 1,
d) bonding the flat substrate to the replica of step c). The method according to claim 1,
Wherein the replica uses a casting method, a hot embossing method, or an injection molding method. The method of claim 3,
Wherein the casting method uses a casting method and the gap between the blade and the microfluidic chip mold is adjusted to 100 to 3,000 탆. The method according to claim 1,
Wherein the mixture comprises 90 to 99.9% by weight of a polysiloxane-based polymer or acrylic polymer and 0.1 to 10% by weight of a curing initiator. The method according to claim 1,
Wherein the curing reaction is thermosetting or ultraviolet curing. The method according to claim 1,
Wherein the step (c) forms an opening in which the top and bottom of the replica are open. The method according to claim 1,
And the thickness variation of the cured replica is -5 mu m to +5 mu m. A microfluidic chip comprising a thin film chip replica produced by the method of any one of claims 1 to 8. 10. The method of claim 9,
The microfluidic chip is an assembled microfluidic chip, which further comprises a fixture on top, bottom, top and bottom of the thin film chip replica. 11. The method of claim 10,
An upper fixture including a tube fixing groove and a male screw injection tube;
A thin film chip replica positioned below the upper fixture;
A flat substrate disposed under the thin film chip replica to maintain the shape of the thin film chip replica;
A lower fixture disposed below the flat substrate and including a screw groove;
A male screw inserted into the male screw injection tube of the upper fixture and fixed by the screw groove of the lower fixture;
And a microfluidic chip. 12. The method of claim 11,
The fixing groove for tube connection includes a fixing groove for connecting a sample injection tube to which a sample injection tube is connected, a fixing groove for connecting a reaction solution injection tube to which a reaction solution injection tube is connected, and a solution discharge tube connection groove to which a solution discharge tube is connected. Dick Chip. 13. The method of claim 12,
Wherein the fixing groove for connecting the sample injection tube, the fixing groove for connecting the reaction solution injection tube, and the fixing groove for connecting the solution discharge tube have female threads on the inner wall, and the fixing grooves are perpendicular to the upper surface of the upper fixing frame, A microfluidic chip having a structure penetrating a fixed frame. 12. The method of claim 11,
Wherein the lower fixture includes a screw groove and a flat substrate mounting groove, and the screw groove is fixed by injecting a male screw passed through the male screw injection tube of the upper fixture. 15. The method of claim 14,
Wherein the flat substrate mounting groove is formed as a recessed groove on an upper surface of the lower fixing frame to define a position of the flat substrate. 12. The method of claim 11,
Wherein the male screw includes a metal or a polymer resin and is injected into the screw groove of the lower fixture after being injected into the male screw injection tube and fixed.

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