Method for manufacturing microstructure using centrifugal force and microstructure manufactured by same

Abstract

The present invention relates to a method for manufacturing a microstructure, the method comprising the steps of: (a) preparing a viscous composition on a lower substrate; and (b) applying centrifugal force to the viscous composition to induce extension of the viscous composition, thereby manufacturing a microstructure. According to the present invention, (i) a microstructure having a micro-unit diameter and sufficient effective length and hardness is provided; (ii) any process that may destroy activation of a drug or cosmetic component, such as high-temperature treatment, organic solvent treatment, etc., is avoided; (iii) loss resulting from contact and separation is reduced; (iv) the limitation of aspect ratio of the manufactured microstructure is overcome; (v) the limitation of yield resulting from flatness is overcome; and (vi) microstructures of various shapes can be manufactured.

Claims

1. A method for manufacturing a microstructure, the method comprising: applying a viscous material onto a surface of a substrate; and rotating the substrate about an axis such that the surface faces away from the axis while rotating, which causes the viscous material to extend generally in a direction perpendicular to the surface and away from the axis by centrifugal force applied to the viscous material, thereby providing a microstructure comprising at least one microneedle elongated from and attached to the surface, wherein the method adjusts at least one dimension of the microstructure which is selected from the group consisting of a length, a diameter, and an aspect ratio by adjusting the centrifugal force.

2. The method according to claim 1, wherein the viscous material comprises at least one selected from the group consisting of a biocompatible substance, a biodegradable substance and a drug.

3. The method according to claim 1, wherein applying the viscous material comprises forming at least one drop of the viscous material on the surface.

4. The method according to claim 1, wherein the surface is curved or embossed to provide hills and valleys.

5. The method according to claim 4, wherein the at least one microneedle comprises a plurality of microneedles, wherein the viscous material is applied onto the surface such that the viscous material forms a layer that generally follows contour of the hills and valleys of the surface, wherein rotating the substrate causes the viscous material to extend from areas over the hills of the surface such that at least part of the resulting microneedles are elongated from and attached to the hills of the surface.

6. The method according to claim 1, wherein the substrate is substantially flat.

7. The method according to claim 1, further comprising: providing a device comprising a body and a plurality of through-holes that are extending from a first surface of the body to a second surface of the body; and after applying the viscous material and before rotating the substrate, placing the device on the viscous material such that the viscous material contacts the first surface; wherein rotating the substrate causes the viscous material extend into at least part of the plurality of through-holes.

8. The method according to claim 1, wherein the substrate is referred to as a first substrate, wherein the surface of the first substrate is referred to as a first surface wherein the method further comprises: arranging a second substrate with a second surface such that the second surface opposes and faces the first surface when rotating the first substrate, wherein rotating the first substrate causes the viscous material to extend such that one end of the viscous material contacts and is attached to the second surface while the other end of the viscous material is attached to the first surface.

9. The method according to claim 8, wherein the viscous material is a hydrophilic substance, the first surface is hydrophobic and the second surface is hydrophilic, wherein the method further comprising: moving the second substrate away from the first substrate in the direction, which causes the viscous material is detached from the first surface while the viscous material is attached to the second surface.

10. The method according to claim 8, further comprising moving the second substrate relative to the first substrate in the direction or in another direction perpendicular to the direction, which causes the viscous material to be separated at an intermediate point between the two ends of the viscous material to provide another microstructure.

11. The method according to claim 1, further comprising: depositing a first metal layer over the microstructure to provide a metal-deposited microstructure; plating a second metal layer onto the first metal layer of the metal-deposited microstructure to provide a metal-plated microstructure; and removing hardened viscous material from the metal-plated microstructure to obtain a micro-mold comprising the first metal layer and the second metal layer.

12. A method for manufacturing a microstructure, the method comprising: providing a hollow structure comprising an inner space and an outlet, the hollow structure containing a viscous material within the inner space; and rotating the hollow structure about an axis, which causes at least a portion of the viscous material to move out through the outlet and extend away from the outlet by centrifugal force applied to the viscous material, thereby providing a microstructure comprising a microneedle elongated from and attached to the hollow structure, wherein the method adjusts at least one dimension of the microstructure which is selected from the group consisting of a length, a diameter, and an aspect ratio by adjusting the centrifugal force.

13. The method of claim 12, wherein the hollow structure comprises a piston and further contains another material, wherein the method further comprises: moving the piston to inject the other material into the microstructure while the centrifugal force is applied or after the centrifugal force is applied, wherein the other material comprises a drug, gas or fluid.

Description

DESCRIPTION OF DRAWINGS

(1) FIG. 1 illustrates microstructures formed when a centrifugal force is applied after dropping drops of a viscous composition on a lower substrate in different shapes and contact areas.

(2) FIG. 2 illustrates microstructures formed when the centrifugal force is applied after dropping different amounts of the viscous composition on the lower substrate.

(3) FIG. 3 illustrates a conceptual view of a method for applying the centrifugal force on the lower substrate on which the viscous composition is prepared.

(4) FIG. 4 illustrates microstructures formed when different magnitudes of the centrifugal force are applied.

(5) FIG. 5 illustrates microstructures formed when the viscous composition is coated on the lower substrate including curves or embossed portions of a specific pattern and the centrifugal force is applied.

(6) FIG. 6 illustrates microstructures formed when different rotational acceleration values are applied.

(7) FIG. 7 illustrates microstructures being formed by an application of the centrifugal force regardless of flatness and uniformity of the lower substrate.

(8) FIG. 8a illustrates a plan view of a cover substrate.

(9) FIG. 8b illustrates an embodiment in which the cover substrate is used.

(10) FIG. 9 illustrates an embodiment which further includes an upper substrate.

(11) FIG. 10 illustrates shapes of microstructures formed when a distance between the upper substrate and the lower substrate is varied.

(12) FIG. 11 illustrates shapes of microstructures formed on the upper substrate and the lower substrate in accordance with an amount of time of applying the centrifugal force, according to the embodiment which further includes the upper substrate.

(13) FIG. 12 illustrates shapes of microstructures formed on the upper substrate and the lower substrate in accordance with a magnitude of the centrifugal force being applied, according to the embodiment which further includes the upper substrate.

(14) FIG. 13 illustrates shapes of microstructures formed on the upper substrate and the lower substrate in accordance with an amount of dropped viscous composition, according to the embodiment which further includes the upper substrate.

(15) FIG. 14 illustrates a bevel angle formed when at least one of the lower substrate and the upper substrate is moved and microstructures formed by being connected to each other are cut, according to the embodiment which further includes the upper substrate.

(16) FIG. 15 illustrates microstructures which are formed when one of the upper substrate and the lower substrate is hydrophobic when a hydrophilic viscous composition is used, according to the embodiment which further includes the upper substrate.

(17) FIG. 16 illustrates microstructures which are formed when one of the upper substrate and the lower substrate is hydrophilic when a hydrophobic viscous composition is used, according to the embodiment which further includes the upper substrate.

(18) FIG. 17 illustrates a device for manufacturing a microstructure by centrifugal force.

(19) FIG. 18 illustrates the device for manufacturing a microstructure by centrifugal force which further includes a rotary shaft of a centrifuge and a motor.

(20) FIG. 19 illustrates a shape of a microstructure formed by applying the centrifugal force.

(21) FIG. 20 illustrates microstructures manufactured through the applying of the centrifugal force using the lower substrate and the upper substrate.

(22) FIG. 21 illustrates a result of observing the microstructures manufactured through the applying of the centrifugal force using the lower substrate and the upper substrate with an electron microscope.

(23) FIG. 22 illustrates a solid microstructure manufactured on the lower substrate and a dissolved state of the microstructure four hours after the microstructure is applied to skin, with respect to the manufacturing of the microstructure through the applying of the centrifugal force and using the lower substrate and the upper substrate.

(24) FIG. 23 illustrates a microstructure manufactured on the upper substrate and a dissolved state of the microstructure four hours after the microstructure is applied to skin, with respect to the manufacturing of the microstructure through the applying of the centrifugal force and using the lower substrate and the upper substrate.

(25) FIG. 24 illustrates a result of observing a shape of a microstructure manufactured while changing the magnitude of the centrifugal force being applied.

(26) FIG. 25 is a mimetic view of a method for manufacturing a microstructure which (A) has multi-layers or (B) includes another microstructure inside using the upper substrate on which a microstructure is already formed.

(27) FIG. 26 illustrates a multi-layer microstructure having a plurality of layers manufactured using the upper substrate on which a microstructure is already formed.

(28) FIG. 27 illustrates a method for manufacturing microstructures of a plurality of shapes which further performs the process of manufacturing the microstructure by changing positions of the lower substrate on which the microstructure is formed and the upper substrate, with respect to the method for manufacturing a microstructure using the lower substrate and the upper substrate.

(29) FIG. 28 illustrates the microstructures of a plurality of shapes which are manufactured by the method of further performing the process of manufacturing the microstructure by changing positions of the lower substrate on which the microstructure is formed and the upper substrate, with respect to the method for manufacturing a microstructure using the lower substrate and the upper substrate.

(30) FIG. 29 illustrates a mimetic view of a method for manufacturing a microstructure using a hollow structure, which includes a viscous composition discharge unit, instead of the lower substrate, and a method for manufacturing a hollow microstructure through a process of plating the microstructure formed by the above method.

(31) FIG. 30 illustrates a method for forming a microstructure using a lower substrate in a form of a needle instead of dropping or coating the viscous composition on the flat lower substrate.

(32) FIG. 31 illustrates a process of forming a hollow microneedle by simultaneously forming a microstructure using centrifugal force and injecting a gas or fluid through the viscous composition discharge unit and forming an empty space in a microneedle.

EMBODIMENTS

(33) Hereinafter, the present invention will be described in more detail through embodiments. The embodiments are only for describing the present invention in more detail, and it will be apparent to those of ordinary skill in the art that the scope of the present invention is not limited by the embodiments in accordance with the present invention.

EMBODIMENTS

Embodiment 1: Manufacture of Microstructure with High Aspect Ratio Using Centrifugal Force

(34) After coating carboxymethylcellulose (Sigma-Aldrich, Inc.) to a polystyrene substrate (SPL Life Science), a viscous solution drop of 40 wt % hyaluronic acid (Soliance) was formed. Then, the substrate was mounted on a centrifuge (Beckman coulter), the centrifuge was accelerated at 5 g/s, and was operated for three minutes at a gravitational acceleration of 900 g. Then, the centrifuge was decelerated at a velocity of 9 g/s. Through the centrifugal force application process, a microstructure with a high aspect ratio was manufactured (reference: FIG. 19) having an effective length of 1,500 m, a top portion diameter of 45 m, and a bottom portion diameter of 300 m.

(35) Meanwhile, a separate process of solidifying the manufactured microstructure was not required, and the solidifying simultaneously occurred in the process of applying the centrifugal force.

(36) Consequently, it can be realized that the microstructure of a high aspect ratio can be successfully fabricated through the centrifugal force application process of the present invention.

Embodiment 2: Manufacture of Microstructure Using Two Substrates (Inner and Outer Substrates)

(37) After discharging 40% (w/v) of 29 kDa hyaluronic acid solution on an aluminum substrate, which is a lower substrate, for 0.220 seconds at a pressure of 0.200 MPa using a dispenser (MUSASHI engineering, ML-5000XII) and forming a solution drop, a centrifuge (Hanil science industrial, Combi 514R) was used to rotate the solution drop between two aluminum substrates, which are respectively the lower substrate and an upper substrate, spaced apart by 1 mm, by a centrifugal force of 500 g for 30 seconds, thereby forming a microstructure (reference: FIG. 20). A left-side figure of FIG. 20 is a microstructure formed on the lower substrate (inner substrate), and a right-side figure of FIG. 20 is a microstructure formed on the upper substrate (outer substrate).

Embodiment 3: Check Microstructure Formation Through Electron Microscope

(38) The microstructure that was manufactured by Embodiment 2 was observed with an electron microscope (Field Emission Scanning Electron Microscope, JSM-7001F, JEOL Ltd., Japan). The microstructures were formed on both the upper substrate and the lower substrate (reference: FIG. 21).

Embodiment 4: Human Body Absorption Evaluation of Microstructure Patch

(39) After applying a microstructure patch manufactured by Embodiment 2 to human body skin, whether the microstructure was absorbed was checked after four hours. FIG. 22 is a result of using the microstructure formed on the lower substrate in Embodiment 2, and FIG. 23 is a result of using the microstructure formed on the upper substrate in Embodiment 2. In both cases, it was confirmed that the microstructures were dissolved and absorbed into the human body.

Embodiment 5: Aspect Ratio Change Test of Microstructure in Accordance with Change in Centrifugal Force

(40) With respect to the manufacturing of the microstructure by the method of Embodiment 2, only the lower substrate was used without the upper substrate, and a shape of a microstructure being formed was observed after applying a centrifugal force of 400 g or 500 g. It was confirmed that the aspect ratio of the formed microstructure was higher in a case of applying the centrifugal force of 500 g than in a case of applying the centrifugal force of 400 g (reference: FIG. 24), and this shows that the shape of the microstructure being formed can be adjusted by adjusting the magnitude of the centrifugal force being applied.

Embodiment 6: Manufacture of Multi-Layer Microstructure

(41) With respect to the method for manufacturing a microstructure of Embodiment 2 in which the lower substrate and the upper substrate are used, the upper substrate on which a microstructure is already formed (reference: upper substrate in FIG. 25) was used to manufacture a microstructure. A multi-layer microstructure was manufactured by a new microstructure being layered on the microstructure that was already formed on the upper substrate (reference: FIG. 26). This shows that the method for manufacturing a microstructure using centrifugal force can be easily applied in manufacturing microstructures of various shapes or manufacturing microstructures formed of a plurality of substances.

Embodiment 7: Manufacture of Microstructures of Plurality of Shapes

(42) With respect to the method for manufacturing a microstructure of Embodiment 2 in which the lower substrate and the upper substrate are used, positions of the lower substrate on which a microstructure is formed and the upper substrate were changed with each other, and the process of manufacturing a microstructure of Embodiment 2 was additionally performed (reference: FIG. 27). By this process, microstructures of two shapes were fabricated on one flat surface (reference: FIG. 28). This shows that microstructures of various shapes can be fabricated on one flat surface through repetition of the manufacture process.

(43) Hereinbefore, particular parts of the present invention have been described in detail. It should be apparent to those of ordinary skill in the art that the detailed description is only a embodiment, and the scope of the present invention is not limited by the description. Consequently, the substantial scope of the present invention should be construed as being defined by the attached claims and their equivalents.