KR20140042968A - Microfluidic device, preparation method of the same, and bioanalytics platform including the same - Google Patents

Abstract

The present invention relates to a microfluidic device, a manufacturing method of the microfluidic device, and a bio-analysis platform using the microfluidic device. According to the present invention, provided are the microfluidic device capable of easily transferring outside solution or blood to the inside of a microchannel by including the hydrophilic microchannel, being easily manufactured, and having relatively low manufacturing costs and the manufacturing method thereof.

Description

TECHNICAL FIELD [0001] The present invention relates to a microfluidic device, a method of manufacturing the same, and a bioanalytical platform including the microfluidic device,

The present invention relates to a microfluidic device, a method of manufacturing the microfluidic device, and a bioanalytical platform including the microfluidic device.

Microfluidic devices fabricated using microfluidics are microchannels (microchannels or nanochannels). Such a microfluidic device allows a small amount of fluid to flow through the microchannel so that various reactions and actions can be performed, so that the operations that have undergone various complicated processes in the existing laboratory can be performed on the chip. For this reason, the microfluidic device may be referred to as a lab-on-a-chip.

Specifically, the microfluidic device is intended to automatically process the whole process of the experiment such as sample injection and hybridization reaction and detection using one small device. In the inside of such a microfluidic device, a single or a plurality of microchannels narrower than hair are formed.

Microfluidic devices can also be applied to a variety of applications of nanobiotechnology, such as analysis and classification of biomolecule materials or single molecule level studies. An example of a method of manufacturing such a microfluidic device is a method of forming a channel using a process such as electron beam lithography and etching and then covering the cover layer with the channel. Such a method must be performed under high temperature and high pressure conditions, It is difficult and expensive to manufacture. For example, Korean Patent Laid-Open Publication No. 2008-0021103 discloses a method of manufacturing a micro-nano fluid element and a MEMS microstructure using an inorganic polymer and a hydrophilic polymer.

Therefore, it is important to reduce the number of processes required for the coupling of the cover layer and the channel layer in manufacturing the microfluidic device, and to secure a space for the channel in which the hydrophilic property essential for introduction of the fluid is maintained for a long time.

The present invention provides a microfluidic device having hydrophilic microchannels, a method of manufacturing the microfluidic device, and a bioanalytical platform including the microfluidic device.

However, the problems to be solved by the present invention are not limited to the above-mentioned problems, and other problems not mentioned can be clearly understood by those skilled in the art from the following description.

According to a first aspect of the present invention, there is provided a pneumatic tire comprising a pumping part forming negative pressure using a restoring force of an elastic body, and a channel part including a microchannel containing a hydrophilic polymer, And an external liquid is introduced into the microchannel and transferred.

According to a second aspect of the present invention, there is provided a method comprising: preparing a cylinder, a pad, and a body; Injecting a hydrophilic polymer onto the template of the microchannel and curing the hydrophilic polymer to form a channel portion; Coating the channel portion with a hydrophobic material; And bonding the cylinder, the pad, the body, and the channel portion to each other.

The third aspect of the present invention can provide a bioanalytical platform comprising a microfluidic device according to the first aspect of the present application.

According to the present invention, it is possible to provide a microfluidic device having a hydrophilic microchannel to easily transfer an external solution or blood into the microchannel, and to manufacture the microfluidic device with ease and with a relatively low manufacturing cost.

Further, the microfluidic device of the present invention can be analyzed rapidly from body fluids such as blood, including bio-chips such as an immune reaction kit, protein array, or peptide array, and the results can be confirmed.

1 is a schematic diagram illustrating components of a microfluidic device according to an embodiment of the present invention.
2 is a schematic view illustrating a process of manufacturing a microfluidic device according to an embodiment of the present invention.
3 is a schematic view showing a process of manufacturing a microfluidic device according to an embodiment of the present invention.
4 is a schematic diagram illustrating a method of using a microfluidic device according to an embodiment of the present invention.
5 is an image of a microfluidic device manufactured according to one embodiment of the present invention.
6 is an image of a microneedle fabricated in accordance with one embodiment of the present application.

Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings so that those skilled in the art can easily carry out the present invention. It should be understood, however, that the present invention may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. In the drawings, the same reference numbers are used throughout the specification to refer to the same or like parts.

Throughout this specification, when an element is referred to as "including " an element, it is understood that the element may include other elements as well, without departing from the other elements unless specifically stated otherwise.

The terms "about "," substantially ", etc. used to the extent that they are used herein are intended to be taken as a reference to either the numerical value or to the numerical value when the manufacturing and material tolerance inherent in the stated meaning is presented, Accurate or absolute numbers are used to prevent unauthorized exploitation by unauthorized intruders of the mentioned disclosure. Also, throughout the present specification, the phrase " to step "or" to step "

Throughout this specification, when a member is " on " another member, it includes not only when the member is in contact with the other member, but also when there is another member between the two members.

Throughout the present specification, the term " combination thereof " included in the expression of the machine form means one or more combinations or combinations selected from the group consisting of the constituents described in the expression of the machine form, Quot; and " the "

The first aspect of the present application, the pumping portion to form a negative pressure (negative pressure) using the restoring force of the elastic body, and a channel portion including a microchannel containing a hydrophilic polymer, and by the sound pressure formed by the pumping portion It is possible to provide a microfluidic device in which external liquid is introduced into and transported into the microchannel.

According to an embodiment of the present invention, the pumping unit includes: a body including a hole; A cylinder which is drawn into the hole of the body by external pressure; And a pad having a restoring force, which is positioned between the body and the cylinder, and which is drawn into the hole according to the pulling of the cylinder, but the present invention is not limited thereto.

According to an embodiment of the present invention, the microfluidic device may further include microneedles, but is not limited thereto. For example, the microneedles may be attached on a circular substrate, but are not limited thereto.

1 is a cross-sectional view of an exemplary embodiment of the present invention wherein the cylinder 110, the pad 130, the body 170, and the hole 150, the channel 190, And the microneedles 210, respectively.

For example, when pressure is applied to the cylinder of the microfluidic device, the cylinder is drawn into the hole with the pad. Thereafter, when the pressure is removed, the cylinder and the pad are restored by the restoring force of the pad, so that a negative pressure is formed in the hole. An external liquid such as blood, body fluids, or a test liquid may be introduced into the inlet of the channel by the sound pressure, and the external liquid may flow into the channel by the hydrophilicity of the channel. .

Since the one end of the micro needle is polished sharply, the micro needle can be inserted into a living body including a human body to collect blood or body fluid, but the present invention is not limited thereto.

In a non-limiting embodiment herein, for ease of entry of the cylinder into the hole, the diameter of the cylinder may be equal to or less than the diameter of the hole.

For example, the channel portion may include, but is not limited to, a microchannel containing a hydrophilic polymer. For example, a hole may be formed at one end of the microchannel included in the channel portion to facilitate introduction of external liquid, but the present invention is not limited thereto. For example, the diameter of the hole may be smaller than the diameter or size of the substrate to which the microneedles are attached, but is not limited thereto. For example, external liquid introduced through the micro needle may be transferred through the hole to the inside of the microchannel through the inlet of the microchannel, but the present invention is not limited thereto.

For example, the channel portion may be coated on one side or both sides thereof by hydrophobic materials, but the present invention is not limited thereto.

According to an embodiment of the present invention, the channel portion may be attached to the body, but the present invention is not limited thereto.

According to one embodiment of the present invention, the hydrophilic polymer may include, but is not limited to, a urethane-based polymer.

According to one embodiment of the present invention, the hydrophilic polymer may include, but is not limited to, NOA (Norland Optical Adhesive). The NOA was purchased from Norland Products Inc. Acrylic resin which is a transparent, colorless and liquid type photopolymerizable polymer compound of acrylated polyurethane type and can be cured by exposure to ultraviolet rays. However, the present invention is not limited thereto. The NOA was purchased from Norland Products Inc. It can be purchased easily from the company. For example, the NOA may be selected from NOA60, NOA61, NOA63, NOA65, NOA68, NOA68, NOA71, NOA72, NOA73, NOA74, NOA75, NOA76, NOA78, NOA81, NOA83H, NOA84, NOA85, NOA86, NOA86H, , NOA13685, NOA1375, NOA138, NOA142, NOA144, NOA148, NOA1625, or NOA164. For example, when the NOA63 is used as the hydrophilic polymer, it can have high strength and high durability.

According to one embodiment of the present invention, the cylinder, the pad, or the body may include a hydrophobic material, but the present invention is not limited thereto.

According to an embodiment of the present invention, the hydrophobic substance may be selected from the group consisting of PDMS (polydimethylsiloxane), polystyrene, polyethylene, polypropylene, polyvinyl chloride (PVC), polytetrafluoroethylene , PTFE), and combinations thereof. However, the present invention is not limited thereto.

According to one embodiment of the present invention, the cylinder, the pad, or the body may include an elastic body, but the present invention is not limited thereto.

According to an embodiment of the present invention, the microneedles may be attached to the channel portion, but the present invention is not limited thereto. For example, the micro needle may be attached to the channel part by a hydrophilic polymer, but is not limited thereto. For example, the microneedles may be attached to a substrate, and the substrate may be attached to the channel portion, but the present invention is not limited thereto. For example, the hydrophilic polymer may include a urethane-based polymer, and the urethane-based polymer may include, but is not limited to, the NOA. For example, the NOA may include, but is not limited to, NOA63. For example, the hydrophilic polymer can be used either as a UV curable adhesive, or as an adhesive commonly used for adhering materials.

According to one embodiment of the invention, the microneedles may include, but are not limited to, those having a length of from about 1 microns to about 5,000 microns and an inner diameter of from about 10 microns to about 100 microns. For example, the microneedles may have a length of from about 1 microns to about 5,000 microns, from about 1 microns to about 4,000 microns, from about 1 microns to about 3,000 microns, from about 1 microns to about 2,000 microns, from about 1 microns to about 1,000 microns, From about 1 micron to about 500 microns, from about 1 micron to about 300 microns, from about 1 micron to about 100 microns, from about 1 micron to about 50 microns, from about 50 microns to about 5,000 microns, from about 100 microns to about 5,000 microns, from about 300 microns About 5,000 mu m, about 5,000 mu m, about 500 mu m to about 5,000 mu m, about 1,000 mu m to about 5,000 mu m, about 2,000 mu m to about 5,000 mu m, From about 1,000 microns to about 2,000 microns, or from about 1,000 microns to about 2,000 microns, such as from about 1,000 microns to about 4,000 microns, from about 1,200 microns to about 3,000 microns, from about 1,500 microns to about 2,500 microns, from about 200 microns to about 2,200 microns, But is not limited thereto. For example, the microneedles may have an inner diameter ranging from about 10 microns to about 100 microns, from about 20 microns to about 100 microns, from about 30 microns to about 100 microns, from about 50 microns to about 100 microns, from about 70 microns to about 100 microns, From about 10 microns to about 70 microns, from about 10 microns to about 50 microns, from about 10 microns to about 30 microns, from about 10 microns to about 20 microns, from about 20 microns to about 80 microns, from about 30 microns to about 70 microns, from about 50 microns Mu] m to about 70 [mu] m, or from about 20 [mu] m to about 40 [mu] m. For example, the micro needle may include a hollow microstructure, which hollow microstructure may include any hollow microstructure known in the art. For example, the micro needle may include, but is not limited to, a hollow microstructure for minimal invasive blood sampling. For example, the microneedles of the present disclosure may have a length of about 1 micron to about 5000 microns, an inner diameter of about 10 microns to about 100 microns, a bevel angle of about 5 degrees To about < RTI ID = But is not limited to, a tip tip angle of about 1 [deg.] To about 45 [deg.], And a tip tip lateral length of about 2 [mu] m to about 30 [ The bevel angle means a tip end portion of the upper end of the microneedle to which the bevel angle is imparted, and the "tip tip end portion" is a point at which a bevel angle is given to the tip end portion of the microneedle, (Refer to FIG. 6). Means a length across the tip tip in the middle of the tip tip and the "tip tip angle" means the angle between the tips in the tip tip. (See FIG. 6). The microneedles may include, but are not limited to, polishing tip tips of the microneedles. Micro-needles can be used to collect blood from subjects, such as mammals, including humans, without pain, minimal trauma, and improved efficiency, but are not limited thereto. The microneedles may have, but are not limited to, tip tip traverses of about 2 [mu] m to about 30 [mu] m. For example, the microneedles may have a tip tip angle of about 1 [deg.] To 45 [deg.], But are not limited thereto.

For example, the microneedles may be attached to a circular, elliptical, or polygonal substrate, but are not limited thereto.

For example, when the micro-fluidic element is brought into contact with a surface of a solution or a surface of a skin of the micro-fluidic element, when the pressure is applied to the cylinder, the cylinder is inserted into the hole of the body together with the pad, The cylinder and the pad embedded in the hole may be returned to their original positions by the elasticity of the pad and the solution or blood may be transferred into the micro-channel and the microchannel of the channel by the generated negative pressure. However, (See FIG. 4). For example, the hydrophilic polymer contained in the microchannel may facilitate transport of the solution or blood, but is not limited thereto.

According to an embodiment of the present invention, the microfluidic device may further include an immune reaction kit, a protein array, a peptide array, or a microfluidic device for specific cell separation, but the present invention is not limited thereto. For example, when an external blood or a body fluid is introduced into the microchannel contained in the microfluidic device, the immune response kit, the protein array, or the peptide array, , A protein, or a peptide is analyzed or detected. For example, the immune response kit, the protein array, or the peptide array may be capable of analyzing or detecting disease related immune substances, proteins, or peptides, but is not limited thereto. For example, the specific microfluidic device for cell separation may include, but is not limited to, a cancer cell, a pre-clinical cancer cell, a cancer cell, or a microfluidic device for stem cell isolation. For example, the cancer cells or stem cells may be cells of mammals including humans, but are not limited thereto.

According to a second aspect of the present invention, there is provided a method comprising: preparing a cylinder, a pad, and a body; Injecting a hydrophilic polymer onto the template of the microchannel and curing the hydrophilic polymer to form a channel portion; Coating the channel portion with a hydrophobic material; And bonding the cylinder, the pad, the body, and the channel portion to each other. For example, the channel portion may be attached to the body but is not limited thereto. For example, the bonding step may be performed through oxygen plasma treatment, but is not limited thereto. For example, the oxygen plasma treatment may be performed at about 30 W to about 150 W, at about 50 W to about 150 W, at about 70 W to about 150 W, at about 90 W to about 150 W, at about 110 W to about 150 W, From about 30 W to about 150 W, from about 30 W to about 130 W, from about 30 W to about 110 W, from about 30 W to about 90 W, from about 30 W to about 70 W, from about 30 W to about 50 W, 50 W to about 90 W, although it is not limited thereto. For example, the oxygen plasma treatment may be performed for about 20 seconds to about 80 seconds, about 20 seconds to about 70 seconds, about 20 seconds to about 60 seconds, about 20 seconds to about 50 seconds, about 20 seconds to about 40 seconds, From about 30 seconds to about 30 seconds, from about 30 seconds to about 80 seconds, from about 40 seconds to about 80 seconds, from about 50 seconds to about 80 seconds, from about 60 seconds to about 80 seconds, from about 70 seconds to about 80 seconds, But it is not limited thereto.

For example, the cylinder may be a cylinder, an elliptical column, or a polygonal columnar elastic body, but is not limited thereto. For example, the pad may be a thin, elastic, round, elliptical, or polygonal elastic body, but is not limited thereto. For example, the hole may include, but is not limited to, a cylinder, an elliptical column, or a polygonal hole. For example, the pad may have a thickness of from about 0.2 mm to about 3 mm, but is not limited thereto. For example, the body may be a polyhedron, a cylinder, an elliptic cylinder, or a polygonal elastic body or an inelastic body, but may have a hole penetrating the body, but is not limited thereto.

According to one embodiment of the present invention, the hydrophilic polymer may include, but is not limited to, a urethane-based polymer.

According to one embodiment of the present invention, the hydrophilic polymer may include, but is not limited to, NOA (Norland Optical Adhesive). For example, the NOA may be selected from NOA60, NOA61, NOA63, NOA65, NOA68, NOA68, NOA71, NOA72, NOA73, NOA74, NOA75, NOA76, NOA78, NOA81, NOA83H, NOA84, NOA85, NOA86, NOA86H, , NOA13685, NOA1375, NOA138, NOA142, NOA144, NOA148, NOA1625, or NOA164.

According to one embodiment of the present invention, the cylinder, the pad, or the body may include a hydrophobic material, but the present invention is not limited thereto.

According to an embodiment of the present invention, the hydrophobic substance may be selected from the group consisting of PDMS (polydimethylsiloxane), polystyrene, polyethylene, polypropylene, polyvinyl chloride (PVC), polytetrafluoroethylene , PTFE), and combinations thereof. However, the present invention is not limited thereto. For example, in the case of the PDMS, adhesion of PDMS to each other can be easily performed through oxygen plasma treatment, but not limited thereto.

According to an embodiment of the present invention, the step of adhering the cylinder, the pad, the body, and the channel part may include treating the surface to be adhered with oxygen plasma to adhere thereto, It is not. For example, the step of coating the channel part with a hydrophobic material may include coating one surface or both surfaces of the channel part, but the present invention is not limited thereto. For example, the hydrophobic material may include, but is not limited to, PDMS. For example, when the channel portion includes NOA and the body includes PDMS, since NOA and PDMS are difficult to adhere by a general method, one or both sides of the channel portion may be coated with a material including PDMS But it is not limited thereto.

According to one embodiment of the present invention, it is possible to further include, but not limited to, bonding the microneedles to the channel portion. For example, adhesion of the micro-needle to the channel portion can be performed using any of UV-curing agents, or adhesives commonly used for bonding materials, but the present invention is not limited thereto. For example, the ultraviolet curing agent may include, but is not limited to, NOA. For example, the NOA may include, but is not limited to, NOA63.

For example, the microneedles may be attached to a substrate, and the substrate may be bonded to the channel portion, but the present invention is not limited thereto.

According to one embodiment of the invention, the microneedles may include, but are not limited to, those having a length of from about 1 microns to about 5,000 microns and an inner diameter of from about 10 microns to about 100 microns. For example, the microneedles may have a length of from about 1 microns to about 5,000 microns, from about 1 microns to about 4,000 microns, from about 1 microns to about 3,000 microns, from about 1 microns to about 2,000 microns, from about 1 microns to about 1,000 microns, From about 1 micron to about 500 microns, from about 1 micron to about 300 microns, from about 1 micron to about 100 microns, from about 1 micron to about 50 microns, from about 50 microns to about 5,000 microns, from about 100 microns to about 5,000 microns, from about 300 microns About 5,000 mu m, about 5,000 mu m, about 500 mu m to about 5,000 mu m, about 1,000 mu m to about 5,000 mu m, about 2,000 mu m to about 5,000 mu m, From about 1,000 microns to about 2,000 microns, or from about 1,000 microns to about 2,000 microns, such as from about 1,000 microns to about 4,000 microns, from about 1,200 microns to about 3,000 microns, from about 1,500 microns to about 2,500 microns, from about 200 microns to about 2,200 microns, But is not limited thereto. For example, the microneedles may have an inner diameter ranging from about 10 microns to about 100 microns, from about 20 microns to about 100 microns, from about 30 microns to about 100 microns, from about 50 microns to about 100 microns, from about 70 microns to about 100 microns, From about 10 microns to about 70 microns, from about 10 microns to about 50 microns, from about 10 microns to about 30 microns, from about 10 microns to about 20 microns, from about 20 microns to about 80 microns, from about 30 microns to about 70 microns, from about 50 microns Mu] m to about 70 [mu] m, or from about 20 [mu] m to about 40 [mu] m.

The third aspect of the present invention can provide a bioanalytical platform comprising a microfluidic device according to the first aspect of the present application. For example, the bioassay platform may be for detecting or characterizing the presence of biomolecules such as immunological material, protein, or peptide, but is not limited thereto. For example, the bio-analytical platform may be, but is not limited to, be capable of analyzing or detecting immune substances, proteins, or peptides associated with a disease. For example, the bio-analysis platform may include, but is not limited to, cancer cells, or microfluidic devices for separating specific cells including stem cells.

Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited thereto.

[ Example ]

1. Manufacture of cylinder

The PDMS (polydimethylsiloxane) sylgard 184 reagent was mixed so that the ratio of the base to the curing agent was 10: 1, the bubbles were removed, and the plate was cured in an oven at 80 ° C for 2 hours. Then, the cured PDMS was cut into a cylindrical shape having a diameter of 6 mm using a biopsy punch to prepare a cylindrical PDMS cylinder having a diameter of 6 mm and a height of 5 mm.

2. Manufacture of pads

The PDMS sylgard 184 reagent was mixed so that the ratio of the base to the curing agent was 10 to 1, then the bubbles were removed, and the amount of the base was set so as to be 1 mm on the plate. The mixture was cured in an oven at 80 ° C for 2 hours . Thereafter, the cured PDMS pads were cut with a knife to a desired size to prepare PDMS pads having a thickness of 1 mm.

3. Manufacturing of the body

The PDMS sylgard 184 reagent was mixed so that the ratio of the base to the curing agent was 10 to 1, and then the bubbles were removed. The amount of the base was set to 5 mm on the plate, and the mixture was cured in an oven at 80 ° C for 2 hours . Thereafter, the cured PDMS pad was cut into a desired size with a knife, and a hole having a diameter of 8 mm was formed at one end of the hole using a biaxial punch to form a hole, and a 5 mm-thick body having a hole having a diameter of 8 mm was manufactured .

4. Channel portion  Produce

end. Fabrication of microchannels

After a small amount of NOA63 prepolymer was injected onto a PET (polyethylene terephthalate) film, a PDMS mold having an embossed line pattern to be a microchannel template was formed and pressure was applied thereto to remove air bubbles between the mold and the NOA63 prepolymer. The pattern formed on the mold was transferred onto the NOA63 prepolymer. Then, the patterned NOA63 prepolymer was cured by exposure to ultraviolet rays for about 2 hours, and the PDMS mold was removed from the cured NOA63 polymer to obtain fine channels of NOA63 formed on the PET film.

I. PDMS  coating

The PDMS included in the body and the NOA 63 included in the channel portion are hardly adhered to each other by a general method, but PDMS can be easily adhered to each other through oxygen plasma treatment. Therefore, The surface of the channel portion except the inside of the channel was coated with nano-thick PDMS to facilitate adhesion of the portion.

The surface of the NOA 63 on which the microchannel was formed was subjected to oxygen plasma treatment at 70 W for 40 seconds, and then the aminosilane diluted to 0.5 wt% in distilled water or methanol was sprayed evenly onto the surface of the NOA 63 and reacted for 20 minutes. After 20 minutes, the surface of the NOA 63 was washed with distilled water or methanol, and then dried under a nitrogen gas atmosphere. (Monoglycidyl ether-terminated PDMS) having a monoglycidyl ether at its end was uniformly sprayed on the surface of the NOA 63 having a monosilane monolayer formed on its surface by the above-mentioned process. Thereafter, a hot plate of 80 ° C to 90 ° C And PDMS was coated on the surface of NOA63. Then, the coated NOA63 was impregnated with isopropyl alcohol and placed on a sonicator for 1 minute to wash the PDMS having monoglycidyl ether at the terminal of the NOA63 that did not react at the surface. Next, the coated NOA 63 was dried in a nitrogen atmosphere, and then a hole having a diameter of 5 mm was drilled at one end of the microchannel to form a channel portion containing NOA63 inside the channel coated with PDMS.

5. Micro needle  Produce

Solid microstructures were prepared using SU-8 2050 photoresist (Microchem) with a viscosity of 14,000 cSt. SU-8 2050 was coated on the metal and silicon substrates at 1000 탆 and 2000 탆, respectively, and then maintained at 120 캜 for 5 minutes to maintain the fluidity of the SU-8, and then contacted with a 3X3 patterned frame having a diameter of 200 탆 . The coated SU-8 2050 has a viscosity sufficient to allow lifting while slowly lowering the substrate temperature to 70 ° C to 60 ° C. At that time, the lifting frame was lifted at a speed of 10 mu m / s for 5 minutes to prepare an initial solid structure of 3,000 mu m. The initial solid structure formed could be separated from the lifting frame by increasing or cutting the second lifting speed. As a result, the initial 1,000 mu m coating thickness of the solid microstructure having an upper end diameter of 30 mu m, a lower end diameter of 200 mu m and a length of 1,500 mu m was measured. The initial 2,000 mu m coating thickness was measured using a solid micro- The structure was prepared and chemically deposited with Tollen ' s reagent. Next, the upper end of the solid micro needle was protected with enamel or SU-8 2050. The enamel or SU-8 2050 treatment on the top part is to prevent the top part from being plated in subsequent steps, and can be made into a hollow type by metal-plated laser and micro-saw cutting of the entire solid microstructure. Next, the surface of the solid micro needles protected at the upper end was electrolytically plated with nickel. The nickel electroplating was performed for 75 minutes at 0.206 μm / min per 1 A / dm ² , so that the thickness of the plated metal was 20 μm. Subsequently, the upper portion of the solid microstructure plated by laser cutting was cut vertically (at an angle of 0 DEG), at an angle of 75 DEG, at an angle of 45 DEG, at an angle of 60 DEG, and at an angle of 15 DEG, A hollow micro needle was completed by removing the SU-8 2050 solid microstructure by placing it in a -8 Remover (Microchem) for about 1 hour. Thereafter, the tips of the hollow micro needles were cut in three directions so that the tip end tip lateral length was 10 占 퐉 or 8 占 퐉, and the substrate portion was cut into a disk shape using a laser to form a hollow type Microneedles were prepared.

From the initial 1,000 mu m coating thickness, a hollow micro needle for an ultra-invasive blood sampling having an upper end outer diameter of 70 mu m, an inner diameter of 30 mu m, a lower end diameter of 200 mu m and a length of 1,500 mu m was extruded from an initial 2,000 mu m coating thickness, A hollow micro needle for the minimal invasive blood sampling with a bottom diameter of 200 탆 and a length of 1,500 탆 was prepared. The hardness of the prepared hollow micro needle showed a value of 1 N to 2 N, which was much larger than the hardness value of 0.06 N penetrating the skin. 6 is an image of the manufactured micro needle.

Alternatively, hollow microsurgical micro-needles for minimally invasive blood sampling having different outer diameters, inner diameters, lower end diameters, or lengths were manufactured and used in the same manner as above. The hollow metal micro- There was a change in the inner diameter, the bevel angle, the tip of the tip tip, and / or the tip tip angle.

6. Fabrication of microfluidic devices

The cylinder, the pad, the body, the channel portion, and the microneedles were combined to finally produce a microfluidic device. Since the cylinder, the pad, the body, and the channel portion included PDMS on the surface, oxygen plasma of 70 W was simultaneously treated on two surfaces to be bonded for 40 seconds, and then each surface was immediately contacted to be adhered. The adhesion order of the cylinder, the pad, the body, and the channel portion at the time of manufacturing the microfluidic device is irrelevant, but is conveniently performed as follows:

One surface of the body and a channel of the channel portion were formed and one surface of the PDMS coating was bonded with an oxygen plasma treatment so that the holes of the body and the holes of the channel portion penetrated. Then, the other surface of the body and one surface of the pad were bonded by oxygen plasma treatment. Finally, the other surface of the pad and one side of the cylinder were bonded by oxygen plasma treatment so that the cylinder was positioned at the hole portion of the body (see FIG. 2).

After attaching the cylinder, the pad, the body, and the channel part to each other, the microneedles were attached to the positions of the holes included in the channel part. NOA63, which is an ultraviolet ray-curable adhesive, was applied along the circumference of the circular substrate of the microneedles and exposed to ultraviolet rays for about 1 hour to cure the micro-needles, thereby attaching the microneedles to one side of the channel portion. 5 is a microfluidic device manufactured by the method of this embodiment.

It will be understood by those of ordinary skill in the art that the foregoing description of the embodiments is for illustrative purposes and that those skilled in the art can easily modify the invention without departing from the spirit or essential characteristics thereof. It is therefore to be understood that the above-described embodiments are illustrative in all aspects and not restrictive. For example, each component described as a single entity may be distributed and implemented, and components described as being distributed may also be implemented in a combined form.

The scope of the present invention is defined by the appended claims rather than the detailed description, and all changes or modifications derived from the meaning and scope of the claims and their equivalents should be interpreted as being included in the scope of the present invention .

110: cylinder
130: pad
150: hole
170: Body
190:
210: Micro needle

Claims (19)

A pumping unit for forming a negative pressure using a restoring force of the elastic body, and
Channel section comprising microchannels containing hydrophilic polymer
Lt; / RTI >
The external liquid is introduced into the fine channel and transported by the negative pressure formed by the pumping unit,
Microfluidic device.
The method according to claim 1,
The pumping unit includes:
A body including a hole;
A cylinder which is drawn into the hole of the body by external pressure; And
A piston having a restoring force, which is located between the body and the cylinder, and which is drawn into the hole when the cylinder is pulled,
The microfluidic device.
3. The method of claim 2,
And the channel portion is attached to the body.
The method according to claim 1,
Wherein the hydrophilic polymer comprises a urethane-based polymer.
3. The method of claim 2,
Wherein the cylinder, the pad, or the body comprises a hydrophobic material.
6. The method of claim 5,
The hydrophobic substance may be selected from the group consisting of PDMS (polydimethylsiloxane), polystylene, polyethylene, polypropylene, polyvinyl chloride (PVC), polytetrafluoroethylene (PTFE) Wherein the microfluidic device is selected from the group consisting of:
3. The method of claim 2,
Wherein the cylinder, the pad, or the body comprises an elastic body.
The method according to claim 1,
The microfluidic device further comprises a microneedle.
The method of claim 8,
And the microneedle is attached to the channel portion.
The method of claim 8,
Wherein the micro needle has a length of 1 탆 to 5,000 탆 and an inner diameter of 10 탆 to 100 탆.
The method according to claim 1,
Wherein the microfluidic device further comprises an immune response kit, a protein array, a peptide array, or a microfluidic device for specific cell separation.
Preparing a cylinder, a pad, and a body;
Injecting a hydrophilic polymer onto the template of the microchannel and curing the hydrophilic polymer to form a channel portion;
Coating the channel portion with a hydrophobic material; And
Bonding the cylinder, the pad, the body, and the channel portion
/ RTI >
A method of manufacturing a microfluidic device.
13. The method of claim 12,
Wherein the hydrophilic polymer comprises a urethane-based polymer.
13. The method of claim 12,
Wherein the cylinder, the pad, or the body comprises a hydrophobic material.
15. The method of claim 14,
The hydrophobic substance may be selected from the group consisting of PDMS (polydimethylsiloxane), polystylene, polyethylene, polypropylene, polyvinyl chloride (PVC), polytetrafluoroethylene (PTFE) And the second electrode layer is selected from the group consisting of silicon oxide and silicon oxide.
13. The method of claim 12,
Wherein the step of bonding the cylinder, the pad, the body, and the channel part includes treating the surfaces to be bonded with oxygen plasma to bond them.
13. The method of claim 12,
Further comprising adhering the microneedle to the channel portion.
The method of claim 17,
Wherein the micro needle has a length of 1 탆 to 5,000 탆 and an inner diameter of 10 탆 to 100 탆.
A bioanalysis platform, comprising the microfluidic device according to claim 1.

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