KR101575593B1 - Fibrous Network-based Microfludic Device and Use Thereof - Google Patents

Abstract

The present invention relates to a fibrous network-based microfluidic device and its use, and more particularly, to a microfluidic device capable of controlling the flow rate of a fluid by controlling the size of a fiber network with pressure and its use.
According to the present invention, a fibrous network-based microfluidic device is capable of sequentially transferring a plurality of fluids by easily controlling the flow rate of a fluid, thereby achieving cleaning, reaction, and detection processes with a single loading. It can be used on an industrial scale in fields such as pregnancy diagnosis using a test method, blood glucose test and detection of harmful microorganisms.

Description

Fibrous network-based microfluidic device and use thereof

The present invention relates to a fibrous network-based microfluidic device and its use, and more particularly, to a microfluidic device capable of controlling a flow rate of a fluid by controlling a pore size formed in fabricating a fibrous network by using pressure, will be.

Immunochromatographic lateral flow strip test using lateral flow can be used for pregnancy diagnosis or urinalysis using low-cost paper-based materials and visual confirmation of test results. And there are many developments and applications because of the advantage that the strip can be kept in a dry condition for a long period of time. However, such a conventional simple immunoassay method has been developed for a single substance or has not reached the sensitivity required for clinical application.

On the other hand, the conventional simple to increase the detection sensitivity of the immunological assay gold nanoparticle to enhance the detection limit signal enhancer (Lu Y, et al , Anal Chem, 82:... 329, 2010) or a method using chemiluminescent (Cho IH, et al., Anal. Chim. Acta, 632: 247, 2009) have been developed, but these have become a problem in automation due to the need for sequential sample loading, washing, and incubation procedures. In order to carry out multiple liquids required for the test in a single loading and to automate the test, a pad containing the substrate required for the test is attached to the fluid transfer section (Joung HA, et al., Biosens. Bioelectron. (Lutz B, et al., Lab Chip 13: 2840, 2013), the paper fluid channel is wetted with pre-liquefied sugar and then dried to selectively slow down the flow rate of the fluid (Jahanshahi-Anbuhi S, et al., Lab Chip 12: 5079, 2012). However, conventionally used methods for adjusting the flow rate in a paper-based fluid channel have a problem in that mass production is difficult because of the high complexity of the process.

The present inventors have made extensive efforts to develop a microfluidic device capable of increasing the sensitivity of the test and lowering the detection limit by a simple method. As a result, it has been found that by controlling the size of the pores formed in the fabrication of the fiber network using the pressure, And the present invention has been completed.

It is an object of the present invention to provide a fiber network-based microfluidic device capable of controlling the flow rate of a fluid by a simple method and its use.

In order to accomplish the above object, the present invention provides an injection apparatus comprising: (a) an injection unit for injecting and reserving a fluid; (b) a first moving part 120 for detecting a component to be detected; (c) a second moving part 130 for controlling the flow rate of the fluid; And (d) a discharge unit 140 through which the sample moved through the moving unit is stored and discharged.

The present invention also provides a fluid flow rate control method using the fibrous network-based microfluidic device.

The present invention also provides a simple immune diagnosis method using the fiber network-based microfluidic device.

According to the present invention, a fibrous network-based microfluidic device is capable of sequentially transferring a plurality of fluids by easily controlling the flow rate of a fluid, thereby achieving cleaning, reaction, and detection processes with a single loading. It can be used on an industrial scale in fields such as pregnancy diagnosis using a test method, blood glucose test and detection of harmful microorganisms.

1 is a schematic diagram of a fiber network based microfluidic device [(a): a standard fiber network based microfluidic device; (b): a fiber network-based microfluidic device having a plurality of second moving parts 130].
FIG. 2 is an analysis of the movement of a fluid according to a pressure applied to a moving part in fabricating a fibrous network-based microfluidic device. [(A) Image of fluid movement distance according to applied pressure at 30 seconds after loading; (b): graph showing the moving distance of the fluid as a function of time].
3 is a schematic view for explaining sequential transfer of various solutions using a fiber network-based microfluidic device.
Figure 4 illustrates the directional control of fluid flow due to formation of a barrier 150 of a fiber network based microfluidic device. (A) When a fluid is dropped on the inner (upper) portion of the barrier 150; (b): a fluid is dropped in the middle of the barrier 150].
5 is a schematic view showing a method of applying pressure to a microfluidic device [(a): a schematic view showing partial pressure application for speed regulation; (b): schematic diagram showing barrier 150 formation).

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In general, the nomenclature used herein is well known and commonly used in the art.

In one aspect of the present invention, there is provided an injection apparatus including: (a) an injection unit 110 in which a sample fluid is injected and reserved; (b) a first moving part 120 for detecting a component to be detected; (c) a second moving part 130 for controlling the flow rate of the fluid; And (d) a discharging unit (140) for discharging and discharging the sample moved through the moving unit, wherein in the fabrication of the fiber network of the first moving unit and the second moving unit, The microfluidic device is fabricated in such a way that the size of the pores is made different from each other.

In the present invention, the fiber network material is selected from the group consisting of materials having a polymer network based on a polymer material such as polypropylene, nitrocellulose, polyvinylphenol, and polystyrene. .

In the present invention, the fiber network process may be carried out by a chemical bonding method, a thermal bonding method, an airlaying method, a wet laid method, a needle punching method, a water flow bonding method, a spun bond method, a melt blowing method, a stitch bond method, But the present invention is not limited thereto.

In the present invention, the microfluidic device can control the size of the fiber network gap by the pressure, and the pressure is applied by a method selected from the group consisting of a hand press, an air press, and a clamp. Preferably, a hand press was used.

In an embodiment of the present invention, a hand press is used to fabricate a microfluidic device, and a load cell is provided on the bottom for pressure measurement. In order to fabricate the microfluidic device of the present invention, an aluminum plate is placed on a load cell, a fiber network-based microfluidic device is sandwiched between two acrylic plates suitable for the size of a microfluidic device to be fabricated, And a microfluidic device having the second moving part 130 was manufactured by applying pressure.

In the present invention, the fluid may be selected from the group consisting of a sample to be inspected, a buffer for washing, and a material for increasing a signal of a test result.

In the present invention, a plurality of injection units 110 may be provided.

In the present invention, the first moving unit 120 includes a coloring component zone 160 that can be combined with a component to be detected, and a detection zone 170 And a control unit for controlling the display unit.

In the present invention, a plurality of the second moving units 130 may be provided, and the sizes of the fiber network pores may be different from each other.

In the present invention, three injection units 110, three second moving units 130, a first moving unit 120, and a discharging unit 140 having different sizes of pores of the fiber network, ) Was fabricated. The fluid of the injection unit 110 connected to the second moving unit 130 having the largest pore size of the fiber network of the second moving unit 130 is moved first and the fluid of the fiber network of the second moving unit 130 is sequentially moved The fluid moves in order of pore size. The first fluid reaches the first moving part 120, and a component to be detected in the sample is combined with a coloring component 160 (160). The fluid may show a color reaction in the detection zone 170, The washing buffer is flowed to wash the sample remaining in the first moving part 120. Finally, the enhancer moved to the second moving part 130 having the smallest fiber network moves the coloring reaction of the detection component contained in the detection zone And it is possible to confirm the component to be detected with high sensitivity and low detection limit.

In the present invention, the pore sizes of the networks of the first moving part 120 and the second moving part 130 are made different from each other by the pressure applied at the time of fabrication, and the size of the fiber network pores of the second moving part is And is smaller than or equal to the size of the fiber network pore of the moving part.

In another embodiment of the present invention, a microfluidic device having a second moving part 130 having a different pore size is manufactured at different pressures to control the fluid flow rate. As the pore size of the fiber network decreased, the flow rate of the fluid decreased as the microfluidic device with four different pore size second moving parts was applied at a pressure of 0, 6.5, 13.1, and 19.6 MPa. Respectively.

In the present invention, the fibrous network-based microfluidic device is surrounded by a barrier 150, and the barrier is physically bonded between the fibrous networks to prevent fluid flow out of the microfluidic device.

In the present invention, a microfluidic device surrounded by the barrier 150 was fabricated. As a result of injecting the food coloring solution into the upper or middle portion of the microfluidic device having one or six channels, it was confirmed that the solution moves according to the shape of the barrier 150 without flowing out of the fluid.

In another aspect, the present invention relates to a method for analyzing a desired component in a sample using a fibrous network-based microfluidic device.

By using the fibrous network-based microfluidic device of the present invention, it is possible to sequentially transfer a plurality of samples by controlling the velocity of the flow flowing through the reduced-size portion of the cavity, and to detect the components in the sample with high sensitivity.

In another aspect, the present invention relates to a method for detecting harmful microorganisms using a fiber network-based microfluidic device.

In another aspect, the present invention relates to a pregnancy diagnosis, blood sugar test or harmful microorganism detection kit comprising a fiber network-based microfluidic device.

In another aspect, the present invention relates to a biochip comprising a fibrous network-based microfluidic device.

Example 1 Fabrication of Microfluidic Device Based on Fiber Network

A hand press (Samwoo Press, Siheung, Korea) was used to fabricate a fibrous network-based microfluidic device for controlling the flow rate of the fluid of the present invention. In the bottom portion of the hand press, a load cell , Curiosity Technology, Paju, Korea) were provided to measure the applied pressure (Fig. 5 (a)). In order to fabricate a microfluidic device having a second moving part 130 in which the pore size of the fiber network is reduced by pressure, an aluminum plate is placed on a load cell, and two sheets of microfluidic devices The fibrous network-based microfluidic device was sandwiched between the acrylic plates and then put on an aluminum plate to apply pressure (FIG. 5 (a)). A fiber network-based microfluidic device having one (FIG. 1 (a)) or a plurality of second moving parts 130 (FIG. 1 (b)) was fabricated as described above.

Further, in order to further manufacture the barrier 140, an aluminum plate was provided on the bottom of the hand press, and then pressure was applied until a barrier was formed using an aluminum mold having the shape of a channel to be manufactured 5 (b)). The aluminum mold can be customized according to the desired channel shape, and can be easily manufactured in various shapes (FIG. 4).
The three moving parts 130a, 130b, and 130c, the first moving part 120, and the discharging part 140 having the barrier 150, (Fig. 3). A sample (for example, a sample containing a harmful microorganism), an injection unit 110, and an injection unit 110 are provided in the injection unit 110 a since the second transfer unit 130 has a fiber network of different sizes (a>b> c) (eg, demineralized water or PBS) and an enhancer (eg, nanoparticle enhancer) in the injection section 110 c, the pore size of the fiber network of the second moving section 130 a The sample contained in the injection unit 110 a first reaches the first moving unit 120. The sample reaches the first moving part 120, and a component to be detected in the sample is combined with a coloring component (160), and the coloring reaction can be observed in the detection zone (170). Thereafter, the washing buffer contained in the injection part 110 b flows through the second moving part 130 b having the second largest pore size of the fiber network to wash the sample remaining in the first moving part 120 Finally, the enhancer included in the injection unit 110 c amplifies the coloring reaction of the detection component contained in the detection zone to the second movement unit 130 c having the smallest fiber network, And low detection limits.

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Example 2: Control of flow rate of fluid according to pore size depending on the magnitude of pressure applied in fabrication of fiber network

In order to control the fluid flow rate of the fiber network-based microfluidic device according to the present invention, a microfluidic device having a second moving part having different pore sizes was fabricated with different pressures (FIG. 2). As a result, the flow rate of the fluid contained in the microfluidic device was found to be slower as the pressure was increased, as shown in FIG. 2 (a). As shown in Fig. 2 (b), when the pressure is not applied, the time taken for the fluid to move 3 cm is about 30 seconds. However, in the case of the microfluidic device to which the pressure of 19.6 MPa is applied, , Indicating that the flow rate has decreased due to the reduced fiber network.

In addition, a microfluidic device having a barrier was fabricated to perform direction control of the fluid flow. A microfluidic device having one or six channels fabricated by the method of Example 1 was fabricated (Fig. 4). As shown in Fig. 4 (a), it was confirmed that when the yellow coloring dye solution was injected into the inside of the barrier (upper end), the fluid migrated to the outside of the barrier without flowing out. In addition, as shown in FIG. 4 (b), it was confirmed that even when the yellow coloring dye solution was injected into the middle portion of the microfluidic device, the solution migrated according to the barrier shape without flowing out the fluid.

While the present invention has been particularly shown and described with reference to specific embodiments thereof, those skilled in the art will appreciate that such specific embodiments are merely preferred embodiments and that the scope of the present invention is not limited thereto will be. It is therefore intended that the scope of the invention be defined by the claims appended hereto and their equivalents.

110:
120: first moving part
130:
140:
150: Barrier
160: color development zone
170: Detection zone

Claims (19)

(a) an injection unit 110 in which a sample fluid is injected and reserved;
(b) a first moving part 120 for detecting a component to be detected;
(c) a second moving part 130 for controlling the flow rate of the fluid; And
(d) a discharge section (140) through which the sample moved through the first moving section or the second moving section is stocked and discharged, wherein the fibers of the first moving section and the second moving section A fiber network based microfluidic device characterized in that the pore size is made different from each other with different applied pressures when fabricating a network.
The method according to claim 1,
Wherein the fiber network material is selected from the group consisting of polypropylene, nitrocellulose, polyvinylphenol, and polystyrene.
Claim 3 has been abandoned due to the setting registration fee. The method according to claim 1,
The fiber network process is performed by a method selected from a chemical bonding method, a thermal bonding method, an airlay method, a wet lay method, a needle punching method, a water flow bonding method, a spun bond method, a melt blown method, a stitch bond method and a resin bond method Fiber network based microfluidic device.
delete The method according to claim 1,
Wherein the pressure is applied by a method selected from the group consisting of a hand press, an air press, and a clamp.
The method according to claim 1,
Wherein the fluid is selected from the group consisting of a sample to be tested, a buffer for washing, and a material for increasing the signal of the test result.
The method according to claim 1,
The fiber network-based microfluidic device of claim 1, wherein the injection unit (110) comprises a plurality of injection units (110).
delete The method according to claim 1,
The first moving unit 120 includes a coloring component zone 160 that can be coupled to a component to be detected and a detection zone 170 that displays a color reaction by collecting color components combined with the component to be detected Fiber network based microfluidic device.
The method according to claim 1,
Wherein the second moving part (130) is a plurality of fiber-network-based microfluidic devices.
11. The method of claim 10,
Wherein the plurality of second moving parts have different fiber network pore sizes.
delete The method according to claim 1,
The fiber network-based microfluidic device of claim 1, wherein the size of the fiber network pores of the second moving part (130) is smaller than or equal to the size of the fiber network pores of the first moving part (120).
The method according to claim 1,
Wherein the fiber network based microfluidic device is surrounded by a barrier (150).
15. The method of claim 14,
Wherein the barrier (150) is in the form of physical bonding between the fiber networks to prevent fluid flow out of the microfluidic device.
A method for analyzing a desired component in a sample using the fiber network-based microfluidic device according to any one of claims 1 to 15.
A method for detecting harmful microorganisms using a fiber network-based microfluidic device according to any one of claims 1 to 15.
15. A kit for detecting pregnancy, blood sugar or a harmful microorganism comprising a fibrous network-based microfluidic device according to any one of claims 1 to 15.
15. A biochip comprising a fibrous network-based microfluidic device according to any one of claims 1 to 15.

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