KR101199303B1 - microfluidic device - Google Patents

Abstract

The present invention provides a microfluidic device. The microfluidic device comprises a storage chamber into which sample fluid is injected and stored; A sensing chamber for sensing a specific substance in the sample fluid; A cleaning liquid storage chamber for storing the cleaning liquid; Flow paths connecting the chambers; And a micropump to transfer the cleaning liquid, it is possible to perform an accurate test even with a small amount of sample fluid.

Microfluidic Control, Plastic Chip, Hydrophobic Valve, Chemical Reaction Pump, Immune Reaction Chip

Description

Microfluidic device

The present invention relates to a microfluidic device.

The present invention is derived from a study conducted as part of the IT source technology development project of the Ministry of Knowledge Economy and the Ministry of Information and Communication Research and Development.

Microfluidic devices are lab-on-the-air, including protein chips, DNA chips, drug delivery systems, micro-total analysis systems, and micro-reactors that require precise and precise fluid control. It is applied to a variety of chips.

In general microfluidic devices, basically, the flow of a fluid based on capillary force is used. In microfluidic devices, it is important to control the rate of movement of the sample fluid in order to improve the sensitivity to certain materials contained in the sample fluid. Various methods have been studied for this purpose, but the conventional microfluidic device requires a large amount of sample fluid, and has difficulty in controlling the fluid transfer speed.

Accordingly, the problem to be solved by the present invention is to provide a microfluidic device capable of accurate inspection with a small amount of sample fluid.

Another object of the present invention is to provide a microfluidic device capable of sequentially controlling the movement of a sample fluid.

The microfluidic device according to the present invention for achieving the above object is a storage chamber in which the sample fluid is added and stored; A sensing chamber for sensing a specific substance in the sample fluid; A cleaning liquid storage chamber for storing the cleaning liquid; Flow paths connecting the chambers; And a micropump transferring the cleaning liquid.

The fine pump may generate gas. At this time, the fine pump, the water contained in a closed fine tank; And citric acid and carbonate positioned around the fine tank, and the fine tank may be formed of a paraffin film. The microfluidic device may further include a fine heater that melts the paraffin film adjacent to the micropump. The microfluidic device may further include a temperature sensor adjacent to the microheater.

The microfluidic device may further include a waste chamber in which the cleaning liquid and the sample fluid transferred by the micropump are disposed.

The microfluidic device may further include a top plate and a bottom plate formed with grooves defining the chambers and the flow path, and a lower end of the top plate may be fused or adhered to the bottom plate. At least one of the upper plate and the lower plate is COC (cyclo olefin copolymer), PMMA (polymethylmethacrylate), PC (polycarbonate), COP (cyclo olefin polymer), LCP (liquid crystalline polymers), PDMS (polydimethylsiloxane), PA (polyamide), PE (polyethylene), PI (polyimide), PP (polypropylene), PPE (polyphenylene ether), PS (polystyrene), POM (polyoxymethylene), PEEK (polyetheretherketone), PES (polyethylenephthalate), PET (polyethylenephthalate), PTFE (polytetrafluoroethylene) , Polyvinylchloride (PVC), polyvinylidene fluoride (PVDF), polybutyleneterephthalate (PBT), fluorinated ethylenepropylene (FEP), and at least one selected from the group consisting of perfluoralkoxyalkane (PFA).

The microfluidic device may further include a filter interposed between the storage chamber and the flow path.

In the microfluidic device, a flow rate of the sample fluid may be controlled by performing hydrophilic or hydrophobic treatment on the flow path.

The microfluidic device may further include a valve part having a width wider than that of the flow path or having a hydrophobic treatment inner surface. The valve portion may have a width wider than the width of the flow path and an inner surface that has been hydrophobized. The valve portion is preferably located at at least one end of the sensing chamber.

In the microfluidic device according to an embodiment of the present invention, after the biochemical reaction for detecting a specific substance in the sample fluid in the sensing chamber by a micropump forcibly transferring the cleaning liquid, particles having a negative effect on the sensitivity may be removed. Thus, accurate inspection can be performed even with a small amount of sample fluid in the microfluidic device.

In addition, in the microfluidic device according to an embodiment of the present invention, the moving speed of the sample fluid may be controlled by the valve unit. In particular, since the valve unit is located at at least one end of the sensing chamber, the length of time that the sample fluid stays in the sensing chamber is increased, thereby improving sensitivity.

Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings. However, the following embodiments are provided to those skilled in the art to fully understand the present invention can be modified in various forms, the scope of the present invention is limited to the embodiments described below It is not.

1 is a plan view of a microfluidic device according to an embodiment of the present invention. 2A is a plan view of the lower plate of FIG. 1. 2B is a plan view of the top plate of FIG. 1. 3 is a cross-sectional view taken along line II ′ of FIG. 1. 4A is a cross-sectional view taken along line II-II ′ of FIG. 1 according to an example of the present invention. 5A is a cross-sectional view taken along line III-III ′ of FIG. 1 according to an example of the present invention.

1, 2A, 2B, 3, 4A, and 5A, the microfluidic device according to the present embodiment includes an upper plate 10 and a lower plate 50. The upper plate 10 and the lower plate 50 are in contact with each other, and the chambers 14, 20, 26, 32, 34, flow paths are formed by grooves formed in the upper plate 10 and / or the lower plate 50. 18 and 24 and valve portions 22 and 30 are defined. The chambers 14, 20, 26, 32, and 34 are a sample storage chamber 14 into which a sample fluid is added and stored, a sensing chamber 20 to detect a specific substance in the sample fluid, and a cleaning liquid storage to store a cleaning liquid. Chamber 32, a fine pump chamber 34 in which the fine pump 36 is stored, and a waste chamber 26 in which the cleaning liquid and the sample fluid are discarded. The cleaning liquid storage chamber 32 is disposed between the fine pump chamber 34 and the sensing chamber 20. The valve parts 22 and 30 may include a first valve part 22 disposed between the sensing chamber 20 and the waste chamber 26, and between the cleaning liquid storage chamber 32 and the sensing chamber 20. It includes a second valve portion 30 disposed in. The flow paths 18 and 24 may include a first flow path 18 connecting the sample storage chamber 14 and the sensing chamber 20, the second valve part 30, and the waste chamber 26. And a second flow passage 24 for connecting therebetween.

Subsequently, an inlet 12 for injecting sample fluid is formed in the upper plate 10 of the sample storage chamber 14, and a filter 16 is disposed between the sample storage chamber 14 and the first flow path 18. Is interposed. The valve parts 22 and 30 have a width wider than that of the flow paths 18 and 24 and have hydrophobic regions 72 and 74 therein. The valve parts 22 and 30 may have a ribbon shape in plan view. That is, the valve parts 22 and 30 may include two regions having a width wider than that of the flow paths 18 and 24 and a hydrophobic treated region 72 positioned therebetween. An air vent 23 may be connected to the first valve part 22. The waste plate 28 may be formed on the top plate 10 of the waste chamber 26. The cleaning liquid and the sample fluid discarded by the waste opening 28 may flow out. The waste outlet 28 may serve as an air vent. The cleaning liquid 70 is stored in the cleaning liquid storage chamber 32. The cleaning liquid 70 may be water.

1, 2A and 3, the fine chamber 36 is positioned in the fine pump chamber 34. The microchamber 36 generates a gas to increase the pressure in the microchamber 34, thereby forcibly transferring the cleaning liquid 70. The fine pump chamber 34 includes water 35a contained in a closed fine tank 35b and a mixture 37 located outside the fine tank 35b. The mixture 37 contains citric acid and carbonate. The fine tank 35b may be made of a paraffin film. The fine tank 35b made of the paraffin film may be melted by heat, and the citric acid and carbonate are dissolved in water as the paraffin film is melted and the water in the fine tank 35b flows out. The citric acid and carbonate react with each other to generate a gas such as carbon dioxide. A fine heater 52 is disposed on the lower plate 50 below the fine pump chamber 34. The fine heater 52 generates heat for melting the paraffin film. A temperature sensor 54 may be disposed on the lower plate 50 to precisely control the temperature of the fine heater 52 adjacent to the fine heater 52. The terminals 52a and 54a of the fine heater 52 and the temperature sensor 54 are not covered with the upper plate 10 and exposed to the outside on the lower plate 50. Surfaces of the fine heater 52 and the temperature sensor 54 may be covered by a protective film (not shown) without being in contact with the fine pump 36. At this time, the heat generated by the fine heater 52 may be transferred to the fine pump 36 through the protective film.

1, 2A, 3, and 5A, at least one sensing electrode 60 may be disposed on the lower plate 50 of the sensing chamber 20. For example, the detection electrode 60 may be coated with a capture antibody that captures the detection antibody to which the gold nanoparticles are fixed. As the number of detection antibodies to which the gold nanoparticles are captured by the capture antibody of the sensing electrode 60 is fixed, the electrical conductivity may increase, and the specific substance may be detected and read using the above points. The sensing electrode 120 may be immobilized with various biochemicals such as antigens, proteins such as antibodies, or genes, and may have a surface treatment such as a self-assembled monolayer. If desired, various chemicals, including dendrimers, may be preformed.

In order to improve the sensitivity of the sensing electrode 60, the amount of sample fluid accumulated in the sensing chamber 20 may be sufficiently increased. One way for this purpose is to insert the intermediate plate 90 between the upper plate 10 and the lower plate 50 as shown in Figure 5b.

 The sensing electrode 60 is connected to the electrode connecting portion 60a and the electrode terminal 60b, and the electrode terminal 60b is not covered by the upper plate 10 and exposed to the outside on the lower plate 50. The electrode connection 60a may be exposed to the outside, but may preferably be covered with a protective film 85 as in FIG. 5A or located in the bottom plate 50 as in FIG. 5B to reduce nonspecific biological binding. The terminal 52a of the fine heater 52, the terminal 54a of the temperature sensor 54, and the terminal 60b of the sensing electrode 60 may be connected to a power supply unit or a measurement unit of an external measuring device.

The upper plate 10 and the lower plate 50 include a cyclo olefin copolymer (COC), polymethylmethacrylate (PMMA), polycarbonate (PC), cyclo olefin polymer (COP), liquid crystalline polymers (LCP), polydimethylsiloxane (PDMS), and PA (PA). polyamide, PE (polyethylene), PI (polyimide), PP (polypropylene), PPE (polyphenylene ether), PS (polystyrene), POM (polyoxymethylene), PEEK (polyetheretherketone), PES (polyethylenephthalate), PET (polyethylenephthalate), PTFE (polytetrafluoroethylene), polyvinylchloride (PVC), polyvinylidene fluoride (PVDF), polybutylene terephthalate (PBT), fluorinated ethylenepropylene (FEP), and at least one selected from the group consisting of perfluoralkoxyalkane (PFA). The upper plate 10 and the lower plate 50 are injection molding, hot embossing, casting, stereolithography, laser ablation, rapid prototyping. ), As well as silkscreen, can be produced by traditional machining methods such as NC (Numerical Control) machining or by semiconductor processing using photolithography and etching. The upper plate 10 and the lower plate 50 may be bonded with an adhesive (80). The adhesive 80 may be a liquid adhesive material or a thin plate adhesive such as powder or paper. When the upper plate 10 and the lower plate 50 are bonded, room temperature or low temperature bonding may be performed to prevent denaturation of a biochemical such as a capture antibody on the surface of the sensing electrode 60. A pressure sensitive adhesive may be used. Alternatively, when the two substrates are bonded at room temperature or at a low temperature in order to prevent denaturation of biochemicals, the end 11 of the top plate 10 is sharply formed as shown in FIG. 4B, and ultrasonic energy is applied to the pointed portions to provide localization. Melting and bonding the upper plate 10 on the lower plate 50 may be performed by a fusion or ultrasonic bonding (ultrasonic bonding) method. Alternatively, as in FIG. 5B, when bonding two or more plates 10, 50, 90, both adhesive 80 and fusion method may be used.

Next, the flow of the fluid in the microfluidic device of FIG. 1 will be described sequentially with reference to FIGS. 6A, 6B, and 6C.

First, referring to FIG. 6A, the sample fluid 100 is introduced through the inlet 12. When the sample fluid 100 is introduced, an antigen or an antibody having a display factor fixed to participate in a biochemical reaction such as an antigen / antibody reaction may be mixed. For example, the sample fluid 100 may be blood, for example. When the sample fluid 100 is introduced, for example, a detection antibody to which gold nanoparticles are fixed may also be added. The cleaning liquid 70 is previously contained in the cleaning liquid storage chamber 32.

Referring to FIG. 6B, when the sample fluid 100 is introduced, the sample fluid 100 moves from the sample storage chamber 14 to the first flow path 18 through the filter 16 in a natural flow by capillary force. Large particles in the sample fluid 100 are filtered out of the filter 16. For example, when the sample fluid 100 is blood, white blood cells and red blood cells are filtered by the filter 16, and small particles such as detection antibodies to which serum or gold nanoparticles are fixed may pass. . The sample fluid 100a filtered by the filter 16 flows to the sensing chamber 20 via the first flow path 18. The sample fluid 100a does not flow toward the cleaning liquid storage chamber 32 by the second valve part 30. This is because the portion of the second valve portion 30 that is in contact with the first flow passage 18 has a wider width than the first flow passage 18, and thus the capillary force is weakened. In addition, since the sample fluid 100a is mostly blood, the sample fluid 100a contains a considerable amount of water. It cannot pass through the second valve part 30. Antigen-antibody reactions within the sensing chamber 20, for example, capture antibodies to which gold nanoparticles are immobilized are captured by the capture antibody. The sample fluid 100a in the sensing chamber 20 does not easily pass toward the second flow path 24 by the first valve part 22. This is because the first valve part 22 also has the same structure as the second valve part 30 and plays the same role. The cleaning liquid 70 may not be transferred toward the sensing chamber 20 by the second valve part 30 unless additionally received a separate force.

Referring to FIG. 6C, when the antigen-antibody reaction occurs sufficiently in the sensing chamber 20, current is supplied to the micro heater 52 by an electronic signal of an external measuring device, and heat is generated in the micro heater 52. Is generated and the paraffin film of the fine pump 36 is melted. And water comes out to dissolve citric acid (C ₆ H ₈ O ₇ ) and carbonate (NaHCO ₃ ), the two react to produce C ₆ H ₇ O ₇ Na, water (H ₂ O) and carbon dioxide (CO ₂ ). have. The pressure of the fine pump chamber 34 rises due to the generation of carbon dioxide, and the cleaning liquid 70 passes through the second valve part 30 to the sensing chamber 20, and the cleaning liquid 70 is transferred to the sensing chamber. It is joined with the sample fluid 100a in 20 and transferred to the waste chamber 28. Thus, the mixed chamber 110b of the cleaning liquid 70 and the sample fluid 100a is stored in the waste chamber 28. The cleaning solution 70 is forcibly transferred to the fine pump 36 to clean the reactants that do not participate in the reaction in the sensing chamber 20 or have weakened the coupling with the sensing electrode 60. 60) sensitivity can be improved. Thus, accurate inspection can be performed even with a small amount of sample fluid in the microfluidic device.

In this embodiment, the micropump includes citric acid and carbonate to generate carbon dioxide, but this is an example, and the micropump includes another mixture to generate carbon dioxide, or the micropump includes oxygen other than carbon dioxide. It will be apparent to those skilled in the art that various gases such as nitrogen may be generated.

As mentioned above, although preferred embodiment of this invention was described in detail, this invention is not limited to the said embodiment, A various deformation | transformation by a person of ordinary skill in the art within the scope of the technical idea of this invention is carried out. This is possible.

1 is a plan view of a microfluidic device according to an embodiment of the present invention.

2A is a plan view of the lower plate of FIG. 1.

2B is a plan view of the top plate of FIG. 1.

3 is a cross-sectional view taken along line II ′ of FIG. 1.

4A is a cross-sectional view taken along line II-II ′ of FIG. 1 according to an example of the present invention.

4B is a cross-sectional view taken along line II-II ′ of FIG. 1 according to another example of the present invention.

5A is a cross-sectional view taken along line III-III ′ of FIG. 1 according to an example of the present invention.

5B is a cross-sectional view taken along line III-III ′ of FIG. 1 according to another example of the present invention.

6A, 6B and 6C are plan views sequentially illustrating the flow of fluid in the microfluidic device of FIG. 1.

Claims (13)

A sample storage chamber into which sample fluid is added and stored; A sensing chamber connected to the sample storage chamber and sensing a specific substance in the sample fluid; A cleaning liquid storage chamber connected to the sensing chamber and storing a cleaning liquid; Flow paths connecting the chambers; And Including a fine pump for transferring the cleaning liquid, generating gas, The fine pump, Water in a closed fine tank; And It includes citric acid and carbonate located around the fine tank, The micro tank is a microfluidic device, characterized in that made of a paraffin film. delete delete The method of claim 1, And a micro heater for applying heat to the micro pump adjacent to the micro pump. The method of claim 1, And a temperature sensor adjacent the micro heater. The method of claim 1, And a waste chamber in which the cleaning liquid and the sample fluid transferred by the fine pump are discarded. The method of claim 1, The microfluidic device further comprising a top plate and a bottom plate formed with grooves defining the chambers and the flow path. The method of claim 7, wherein The lower end of the upper plate is a microfluidic device, characterized in that fused or bonded on the lower plate. The method of claim 7, wherein At least one of the upper plate and the lower plate is COC (cyclo olefin copolymer), PMMA (polymethylmethacrylate), PC (polycarbonate), COP (cyclo olefin polymer), LCP (liquid crystalline polymers), PDMS (polydimethylsiloxane), PA (polyamide), PE (polyethylene), PI (polyimide), PP (polypropylene), PPE (polyphenylene ether), PS (polystyrene), POM (polyoxymethylene), PEEK (polyetheretherketone), PES (polyethylenephthalate), PET (polyethylenephthalate), PTFE (polytetrafluoroethylene) , At least one selected from the group consisting of polyvinylchloride (PVC), polyvinylidene fluoride (PVDF), polybutylene terephthalate (PBT), fluorinated ethylenepropylene (FEP), and perfluoralkoxyalkane (PFA). The method of claim 1, And a filter interposed between the storage chamber and the flow path. The method of claim 1, A hydrophilic or hydrophobic treatment on the flow path to control the feed rate of the sample fluid. The method of claim 1, And a valve portion having a width wider than that of the flow path or having a hydrophobic inner surface. 13. The method of claim 12, And the valve portion is positioned at at least one end of the sensing chamber.

Images