KR100682534B1 - Method for manufacturing microneedle array - Google Patents

Abstract

A method for manufacturing a micro needle array is provided to reduce a manufacturing cost and to prevent a micro needle from being abraded and damaged by manufacturing the micro needle having a sharp end and a high intensity. A method for manufacturing a micro needle array includes the steps of: manufacturing a base of a flat type(S10); depositing an electrical plating seed layer on an upper surface of the base(S11); spreading a photo resist on the electrical plating seed layer(S12); exposing the photo resist to a light ray, developing the exposed photo resist, and exposing the electrical plating seed layer in a pattern of a predetermined shape(S13); performing electrical plating for the exposed electrical plating seed layer(S14); and separating the plating layer formed by the electrical plating(S15).

Description

Microneedle array manufacturing method {METHOD FOR MANUFACTURING MICRONEEDLE ARRAY}

1A is a perspective view showing an example of an in-plane type microneedle array;

1B is a perspective view showing an example of an out-of-plane microneedle array;

Figure 1c is a perspective view showing another example of the in-plane microneedle array,

1D is a perspective view showing an example of an out-of-plane microneedle array;

2 is a flow chart of an embodiment of a method for manufacturing an in-plane microneedle array according to the present invention;

3A to 3E are explanatory diagrams showing respective steps of the embodiment of FIG. 2;

4 is a perspective view showing a base including an inclined surface,

5 is a perspective view showing a base wall formed;

6a and 6b is a perspective view showing a base formed with a ridged,

7 is a flow chart of a first embodiment of a method for manufacturing an out-of-plane microneedle array according to the present invention;

8 is an explanatory diagram showing a manufacturing process according to the embodiment of FIG.

9 is a flow chart of a second embodiment of a method for manufacturing an out-of-plane microneedle array according to the present invention;

10A to 10D are explanatory diagrams showing a manufacturing process according to the embodiment of FIG. 9;

11 is a flowchart of a third embodiment of the method for manufacturing an out-of-plane microneedle array according to the present invention;

12 is an explanatory diagram showing a manufacturing process according to the embodiment of FIG. 11;

13 is a flow chart of a fourth embodiment of a method for manufacturing an out-of-plane microneedle array according to the present invention;

14 is an explanatory diagram showing a manufacturing process according to the embodiment of FIG. 13;

15 is a perspective view of an out-of-plane microneedle array in which wrinkles are formed on a substrate;

16A is a perspective view of a sheet in which wrinkles and holes are formed;

FIG. 16B is a perspective view illustrating the out-of-plane microneedle array to which the sheet of FIG. 16A is attached; FIG.

17 is a perspective view of an out-of-plane microneedle array in which holes are formed in a substrate.

♣ Explanation of symbols for main parts of drawing ♣

10: in-plane type microneedle array 11: attached

11a: slope 11b: side groove

12: base 20: substrate

20a: hole 21a, 21b: recess

22: slot 23, 61: pleat

50: surface external fine needle array 60: sheet

62: hole 90: curable material

100: base 101: inclined surface

102: wall 103: mockup

110: electroplating seed layer 120: photosensitive layer

121, 122: Pattern 130: Plating Layer

The present invention relates to a method for manufacturing a microneedle array, and more particularly, to a method for easily manufacturing an in-plane microneedle array having a complex shape and a method for manufacturing an out-of-plane microneedle array using an in-plane microneedle array. will be.

Conventionally, needles having a diameter of millimeters and a length of centimeters have been used to extract blood from human skin or inject drugs into the body. These needles stimulate many pain points in the skin and cause significant pain to the subject when used.

Microneedles, which are around tens to hundreds of micrometers in diameter and hundreds to thousands of micrometers in length, have a smaller diameter and shorter length than conventional needles, reducing the number of irritating pain points. . In addition, especially for the purpose of drug injection, the subject can be manufactured to a length that can penetrate only to the depth without blood vessels and nerves so that the subject does not feel pain.

When one microneedle is used, the drug delivery efficiency is low or the amount of the substance that can be extracted is very small. As shown in FIGS. 1A and 1B, a plurality of microneedles are arranged in a predetermined arrangement. Used in form. Depending on whether the microneedle is two-dimensional or three-dimensional, it may be classified into an in-plane type microneedle array and an out-of-plane type microneedle array. FIG. 1A illustrates an in-plane microneedle array 10 in which bases 12 of each microneedle 10 'are connected to each other such that the pointed attachment 11 of the microneedle 10' faces the same direction. The attachment 11 is arranged in the same plane as the base 12. FIG. 1B illustrates an out-of-plane microneedle array 50, in which microneedles 10 ′ having a predetermined height protrude to one surface of the substrate 20, and the attachment 11 of the microneedles 10 ′ is formed. It is arranged in a plane different from the substrate 20. The out-of-plane microneedle array is more practical than the in-plane microneedle array because it can control the penetration depth of the microneedle. In addition, the microneedle has an inclined surface 11a formed on the attachment 11 to easily penetrate the skin as shown in FIGS. 1C and 1D, or the microneedle 10 'for blood extraction or drug injection. Hollow or side groove 11b is formed along the longitudinal direction of the may be designed in a complex shape. In addition, as shown in FIG. 1D, in the case of the out-of-plane microneedle, a hole 20a may be formed through the substrate 20 for drug supply.

Conventional methods for fabricating such a microneedle are typical methods using a general semiconductor process, Deep Reactive Ion Etching (DRIE), and UV or X-ray gradient exposure.

Manufacturing method using general semiconductor process and DRIE is 'Fluid Injection through Out-of-plane' presented by Boris Stoeber and Dorian Liepmann at '1st Annual International IEEE-EMBS Special Topic Conference' in Lyon, France in October 2000. Needle '(pp. 224-228) and JGE Gardeniers, JW at MEMS2002 in Las Vegas, January 2002. Bernschot, M.J. Silicon Micromachined Hollow Microneedles for Transdermal Liquid Transfer (pp. 141-144) published by de Boer, Y. Yeshurun, M. Hefetz, R. van't Oever and A. van den Berg, and also MEMS2002 Patrick Griss and Goron Stemme's Novel, Side Opened Out-of-plane Microneedles for Microfluidic Transdermal Interfacing (pp. 467-470).

Methods of fabricating using ultraviolet or X-ray oblique exposure techniques are described in Korean Patent Applications Nos. 10-2003-0003041 and 10-2003-0009768.

However, in the method of manufacturing the microneedle using the semiconductor process and the DRIE, there is a possibility that toxic chemicals used in the semiconductor process remain in the manufactured microneedle. In addition, since the material is a ceramic-based ceramic such as silicon or glass, if the fine microneedles are destroyed by impact or abrasion, and the fragments remain in the body, it may flow through the blood and damage the internal tissues or block blood vessels. In addition, ceramic-based materials reduce the flexibility of the microneedle array, which reduces the adhesion between the array and the skin. In addition, since the semiconductor process and the method using the DRIE process the microneedle shape by controlling the etch rate, it is difficult to precisely control the machining of complex shapes such as the inclined plane with the fine needle or the side groove in the longitudinal direction. Since the shape is determined, there is a limit to the shape which can be manufactured. In addition, the thickness of commercially available silicon and organic substrates is constant at 500 μm and 1000 μm, while the height of the microneedle is limited by the thickness of the substrate, making it difficult to manufacture fine needles of various heights. It takes longer and production costs are very high.

On the other hand, it is difficult to produce microneedles having a height of several hundred micrometers or more by the method using ultraviolet rays, and the method using X-rays does not frequently use X-rays. In addition, although it is possible to form the inclined surface or the side groove in the longitudinal direction with the microneedle, there is a disadvantage that the shape of the microneedle width can not be freely adjusted. The narrower the needle, the smaller the pain on the subject, but the weaker the needle, the weaker the tip of the needle, the width of the center part is constant, and the area close to the substrate increases the width of the needle. It is preferable. However, it is difficult to realize such a shape using a technique using ultraviolet or X-ray oblique exposure technique.

Accordingly, the present invention has been made to solve the above problems, an object of the present invention is to provide a method that can accurately and easily produce in-plane microneedle of a complex shape.

Another object of the present invention is to provide a method for producing an out-of-plane microneedle having a low manufacturing cost by producing an out-of-plane microneedle using an in-plane microneedle.

Still another object of the present invention is to provide an out-of-plane microneedle with a flexible substrate to improve adhesion to skin.

Other objects, specific advantages and novel features of the present invention will become more apparent from the following detailed description and preferred embodiments in conjunction with the accompanying drawings.

In-plane microneedle array manufacturing method according to the present invention comprises the steps of preparing a base of the flat plate shape, depositing an electroplating seed layer on the upper surface of the base, applying a photosensitive agent on the electroplating seed layer, Exposing and developing the electroplated seed layer in a pattern of a predetermined shape, electroplating the exposed electroplated seed layer, and separating the plating layer formed by electroplating. It is characterized by. In the exposure development step, the light rays are X-rays, the photosensitive agent is polydimethylmethacrylate, and before the step of applying the photosensitive agent, the step of forming an adhesion improving layer on the electroplating seed layer, and the liquid polydimethylmeta on the surface of the adhesion improving layer It is preferred to further comprise the step of applying the acrylate. In the exposure developing step, it is preferable to expose the light beam inclined with respect to the upper surface of the photosensitive agent layer.

In addition, the in-plane microneedle array manufacturing method according to the present invention is characterized in that it further comprises the step of forming an inclined surface on the upper surface of the base after the step of manufacturing the base. In this case, the forming of the inclined surface may include forming an oxide film or a nitride film having a predetermined pattern on the upper surface of the base through a photolithography process, and etching the base with an anisotropic etching solution. Alternatively, the step of forming the inclined surface preferably includes a step of projecting a wall on the upper surface of the base, and filling and curing the curable material in the space between the wall and the upper surface of the base.

In addition, the in-plane microneedle array manufacturing method according to the present invention is characterized in that it further comprises the step of forming a narrow concave protruding on the upper surface of the base after the step of manufacturing the base. At this time, the step of forming the ridges, it is preferable to include a step of applying a photosensitive agent on the upper surface of the base, and removing the photosensitive agent leaving only a narrow band shape by photo-etching. Alternatively, the step of forming the gyrus, it is preferable to directly etch the base.

In addition, the in-plane microneedle array manufacturing method according to the present invention is characterized in that it further comprises the step of forming a side groove in the longitudinal direction on one surface of the plating layer separated through a selected process during laser processing or electric discharge processing.

In addition, the in-plane microneedle array manufacturing method according to the present invention is characterized in that it further comprises the step of producing the intaglio mold with the separated plating layer as a circular, and the step of injection molding the polymer into the intaglio mold.

In addition, the in-plane microneedle array manufacturing method according to the present invention is characterized in that it further comprises the step of manufacturing the intaglio mold with the separated plating layer in a circular form, and the step of hot embossing the polymer with the intaglio mold.

In addition, the in-plane type microneedle array manufacturing method according to the present invention, characterized in that it further comprises the step of producing the intaglio mold with the separated plating layer in a circle, and the step of ultraviolet nanoimprinting the monomer in the intaglio mold.

According to an aspect of the present invention, there is provided a method of manufacturing an out-of-plane type microneedle array, which includes manufacturing a plate-shaped substrate, manufacturing an in-plane type microneedle array, and fixing the in-plane type microneedle array vertically on one surface of the substrate. It is characterized by including. At this time, fixing the in-plane microneedle array to the substrate, the step of applying an adhesive to the bottom of the base of the in-plane microneedle array, the step of adhering the in-plane microneedle array coated with the adhesive to one surface of the substrate It is preferable to include. In addition, the manufacturing method of the out-of-plane type microneedle array according to the present invention, it is preferable to further include the step of curing the curable material by the height of the base protruding from one surface of the in-plane type microneedle array array.

In the method for manufacturing an out-of-plane type microneedle array according to the present invention, the step of fixing the in-plane type microneedle array to a substrate may include forming a recess on one surface of the substrate and a base of the in-plane microneedle array on the recess. It is preferred to include the step of accommodating and filling and curing the curable material in the recess. And further including inserting the attachment of the in-plane microneedle array into the plastic plate prior to receiving the base of the in-plane microneedle array into the recess, wherein the step of receiving the base of the in-plane microneedle array into the recess. It is preferable to accommodate the base of the in-plane microneedle array inserted in the plastic plate in the recess.

In addition, according to the present invention, the method for manufacturing an out-of-plane type microneedle array may include fabricating a substrate using an elastic material, and fixing the in-plane microneedle array to the substrate by partially cutting one side of the substrate into a slot. And forming a slot in the slot perpendicular to the slot and extending the base of the in-plane microneedle array into the slot. In this case, the method may further include a step of curing the curable material by pouring the free space formed between the slot and the base of the in-plane microneedle array.

In addition, the method for manufacturing an out-of-plane type microneedle array according to the present invention may further include forming a wrinkled shape on one surface of the substrate before fixing the in-plane type microneedle array to the substrate.

In addition, the method for manufacturing an out-of-plane microneedle array according to the present invention is characterized in that it further comprises the step of forming a through hole in the substrate.

Hereinafter, with reference to the accompanying drawings will be described in detail a preferred embodiment of the in-plane type microneedle array manufacturing method according to the present invention.

2 is a flow chart of one embodiment of a method for manufacturing an in-plane microneedle array according to the present invention, and FIGS. 3A to 3C are explanatory diagrams showing each step of the embodiment of FIG. 2.

First, a base 100 having a flat plate shape is manufactured (S10). The material of the base is preferably silicon.

In order to plate the base 100, an electroplating seed layer 110 is deposited on the top surface of the base 100 as shown in FIG. 3A (S11). The electroplating seed layer 110 is hundreds to thousands of millimeters thick, preferably 2000 millimeters thick titanium layer, and is formed using a sputtering method or an evaporation method.

The photosensitive agent is applied on the electroplating seed layer 110 again to form the photosensitive agent layer 120 (S12). Subsequently, the material and the detailed process of the photoresist layer 120 may vary depending on whether the exposure light is ultraviolet rays or X-rays.

The photoresist layer to be exposed to ultraviolet rays can be easily obtained by using SU-8 50, SU-8 100, etc. among ultraviolet negative photosensitizers under the trade name SU-8. For example, when using a silicon base of 4 inches in diameter, the SU-8 100 is applied by rotating about 1000 rpm for about 40 seconds to the thickness of the photosensitive agent to about 100 ~ 200 micrometers. Heat treatment is performed for 2 to 4 hours in a 95 ° C convection oven to remove the solvent contained in the photosensitizer, and the thermal stress of the photosensitizer may be reduced by slowly raising or lowering the temperature of the oven.

The photosensitive agent layer to be exposed by X-rays may be formed of polymethylmethacrylate (PMMA). That is, the PMMA plate may be bonded onto the electroplating seed layer 110. At this time, in order to improve the adhesion with the PMMA, it is preferable to first form an adhesion improving layer on the electroplating seed layer 110 (S11a). The adhesion enhancement layer is formed by diluting S1805 or AZ5214, which is a photosensitive agent, in acetone at about 1:10 and rotating the coating (300 rpm 15 seconds, 3000 rpm 40 seconds), followed by heat treatment at 90 ° C. for 100 seconds. It is preferable to further form a liquid PMMA layer on the adhesion improving layer (S11b). The liquid PMMA layer is formed by rotating the liquid PMMA (300 rpm 15 seconds, 3000 rpm 40 seconds) and then heat-treating in an oven at 180 ° C. for 1 hour. An X-ray photosensitive agent layer is formed on the liquid PMMA layer (S12). As described above, the X-ray photosensitive agent layer is preferably made of a PMMA plate which is an X-ray photosensitive agent. PMMA plate is bonded to the liquid PMMA layer using methyl methacrylate (MMA). The detailed bonding process is to place the PMMA plate on the liquid PMMA-coated base that has been heat-treated, and then inject MMA therebetween for about 30 minutes at a predetermined pressure (1 to 2 kg on the base of about 5 cm × 5 cm). ) In the order of addition. The PMMA plate may be processed to a desired thickness through grinding, lapping and polishing processes before or after bonding to the liquid PMMA layer. The step of forming the adhesion improving layer (S11a) and the step of forming the liquid PMMA layer (S11b) is necessary only when exposing with X-rays, and not required when exposing with ultraviolet rays.

 After forming the photoresist layer, the planar shape of the microneedle array is masked with a patterned mask to expose ultraviolet rays or X-rays and the photoresist is developed (S13). Then, as shown in FIG. 3B, the photoresist layer 120 is partially removed to expose the electroplating seed layer 110, thereby forming the pattern 121 of the microneedle array in the shape of a mask.

When exposing to ultraviolet rays, the exposure conditions use ultraviolet rays near the wavelength of 365 nm and the exposure amount is preferably 500 to 700 mJ / cm 3. And once again heat treatment is performed for 30 to 90 minutes in a 95 ℃ convection oven. In this case, if the temperature of the oven is gradually raised or lowered, the thermal stress of the photosensitive agent may be reduced. After the heat treatment is completed, if the developer is developed using a developing solution, the photoresist layer 120 having the pattern 121 of the microneedle array may be obtained as shown in FIG. 3B.

When exposing with X-rays, it is preferable to use synchrotron radiation and make the amount of energy accumulated at the bottom of the PMMA layer about 2 to 4 kJ / cm 3. The mask used here is composed of an X-ray absorption layer made of gold having a thickness of several tens of micrometers and a substrate which is an X-ray transmissive layer. The substrate may be silicon, boron nitride (BN), graphite, or the like. When the exposed photoresist layer is developed with the PMMA developer, the photoresist layer 120 having the pattern 121 of the microneedle array may also be obtained as shown in FIG. 3B.

After the exposure and development is completed, a pattern of the microneedle array is formed on the photoresist layer and then electroplated (S14). Nickel is preferred as the material for electroplating. Then, as shown in FIG. 3C, the plated layer 130 having the same shape as the pattern 121 of the microneedle array is formed while nickel is plated on the exposed electroplating seed layer 110. If the unevenness of the upper portion of the plating layer 130 is severe after the electroplating, it is preferable to remove the unevenness through grinding, lapping or polishing processes.

Then, the base 100 and the photoresist layer 120 are etched and removed, or before the electroplating, a material that functions as a release agent is applied or deposited in advance between the base and the electroplating seed layer, and then after the electroplating is completed, the base ( 100 and the plating layer 130 is separated from the photoresist layer 120 (S15). The separated plating layer 130 has a shape of an in-plane type microneedle array as shown in FIG. 1A.

When the light is inclinedly exposed to the upper surface of the photoresist layer in the step S13 of exposing to the photosensitive agent layer 120, as shown in FIG. 3D, the pattern 122 of the microneedle array obtained after development has a side face to the upper surface thereof. It becomes inclined shape. Electroplating the pattern 122 (S14) and separating the plated layer (S15), as shown in FIG. 3E, shows an in-plane type microneedle array in which the side surface 2 is inclined with respect to the upper surface 1. Get As such, the microneedle of the shape of which the side is inclined with respect to the upper surface is more easily attached to the skin, thereby making it easier to penetrate skin.

On the other hand, especially in the case of exposure to ultraviolet light, the step of forming the electroplating seed layer (S11), the step of forming the photoresist layer (S12) and the step of exposing and developing the photoresist layer (S13) must be in a posterior relationship. It is sufficient if it is carried out before each step of electroplating (S14). That is, the electroplating seed layer may be deposited only one layer on the base as in the above-described embodiment, and after the photoresist layer is exposed and developed to form a pattern of the microneedle array (S13), the electroplating seed layer is once more on the photoresist layer. May be deposited. In addition, a photoresist layer may be formed directly on the base (S12) and exposed to form a pattern of a microneedle array (S13), and then an electroplating seed layer may be deposited on the photoresist layer (S11). Release agents that facilitate separation of the base and the electroplated plating layer should be applied or deposited directly under the electroplating seed layer in each case described above. On the other hand, in the case of depositing the electroplating seed layer (S11) after exposing and developing the photoresist layer to form a pattern of the microneedle array (S13), the plating layer 130 is attached to the base 100 or the base ( After removing the electroplated plating layer 130 from 100), grinding, lapping, or polishing processes are performed to remove the electroplating seed layer deposited or deposited on the photoresist layer. You can get it.

As shown in FIG. 4, using the base 100 including the inclined surface 101, forming an electroplating seed layer on the base (S11), and forming a photoresist layer on the electroplating seed layer (S12). After the exposure and development with ultraviolet or X-ray (S13), the electroplating step (S14) and the step of separating the plating layer (S15), respectively, as shown in FIG. 1C, the inclined surface 11a on the attachment 11 is shown. ) Formed fine needle (10 ') can be obtained. Since the microneedle having the inclined surface formed on the attachment is easy to penetrate the skin, it is preferable to form the inclined surface on one surface of the base in step S10 of manufacturing the base.

At this time, there are many ways to manufacture the base including the inclined surface. The first method is to form an oxide film or a nitride film of a predetermined pattern based on a single crystal silicon wafer through a photolithography process, and then etch the single crystal silicon wafer with an anisotropic etching solution. Secondly, the ultraviolet gradient exposure technique is used. Third, as shown in FIG. 5, after forming the wall 102 on one surface of the base 100 or attaching it separately, the material is liquid or low viscosity in a state in which the base is inclined at a predetermined angle, but time passes or A material that is cured through a post-treatment process such as heat treatment or UV treatment, that is, a curable material 90 is poured, and the post-treatment process is performed in an inclined state to produce a base including an inclined surface. The wall 102 may be formed by photolithography after forming a photoresist layer on the base 100, or may be separately attached to the base after the wall 102 is separately made of polydimethylsiloxane (PDMS). As the curable material, a photosensitizer, PDMS or other thermoplastic resin can be used. When the photosensitive agent or PDMS is used as a curable material, the base is tilted at room temperature, and then the photosensitive agent or PDMS is poured into the space between the wall and the base and cured by heat treatment. When the thermoplastic resin is used as a curable material, the molten thermoplastic resin is poured into the space between the wall and the base while the base is heated, or the thermoplastic particles are poured into the space between the wall and the base at room temperature, and then melted by heating. Cool to cure.

As shown in FIG. 1C, when side grooves 11b are formed along one side of the microneedles 10 'along the longitudinal direction of the microneedles 10', drug injection into the human body may be facilitated or extraction of the substance may be performed. To facilitate.

In order to manufacture the microneedle formed with the side grooves along the longitudinal direction as described above, it is preferable to form the ridges 103 as shown in FIG. 6A on one surface of the base 100 in step S10 of manufacturing the base 100. . In this case, as a method for forming a ridge, a photosensitive ridge is formed on a base by a general photolithography process, and the base is etched with an anisotropic etching solution or directly by a dry etching method such as reactive ion etching (RIE). There is a way to process. If the above steps (S11 to S15) are performed using the base 100 on which the grooves 103 are formed, the microneedle array in which the side grooves 11b are formed may be manufactured as shown in FIG. 1C. In addition, the grooves 103 may be formed before the electroplating step S14 to have a shape as shown in FIG. 6B. In this case, the ridges 103 may be formed of a photoresist material through a general photolithography process, or may be formed by depositing a metal or a polymer by using a shadow mask technique. After forming the ridges 103, the electroplating step S14 and the plating layer separation step S15 may be performed, respectively, to obtain an in-plane type microneedle array having side grooves. Meanwhile, after the in-plane microneedle array is completed, the side grooves may be directly formed through a post-processing process. In this case, side grooves are directly formed using laser processing or electro discharge machining.

The in-plane type microneedle array manufactured through the above steps is a material used for electroplating, for example, a metal such as nickel. The metal microneedle array is made into a circle to form a negative mold, and then each of the polymers is injection molded, hot embossed, or UV nanoimprinted with monomers to the ceramic series. In comparison, the microneedle array of the soft material can be produced in large quantities, thereby greatly reducing the manufacturing cost of the microneedle. A more specific method of manufacturing the intaglio mold is as follows. After the PDMS monomer and the curing agent are mixed in a 10: 1 to remove bubbles, the circular microneedle array is submerged, and then the heat treatment process causes the PDMS to cure, and the cured PDMS easily falls out of the circle. If necessary, a release agent may be applied to the prototype or surface treated to make the cured PDMS more easily detached. Intaglio molds, such as the method of manufacturing the intaglio mold as well as the method of applying a release agent to the circle, and then electroplating after forming the electroplating seed layer, the material used as a material of the intaglio mold Various materials can be used without being limited to PDMS.

Hereinafter, a method of manufacturing an out-of-plane type microneedle array according to the present invention will be described in detail.

According to the present invention, a method of manufacturing an out-of-plane type microneedle array may include manufacturing an in-plane type microneedle array, manufacturing a plate-shaped substrate, and fixing the in-plane type microneedle array to one surface of the plate-shaped substrate, Securing the attachment of the needle to a plane different from the substrate surface. In this case, according to a specific method of fixing the in-plane microneedle array to a substrate, the method of manufacturing the out-of-plane microneedle array according to the present invention may be divided into several embodiments as follows.

7 is a flowchart of a first embodiment of an out-of-plane type microneedle array manufacturing method according to the present invention, and FIG. 8 is an explanatory diagram illustrating a manufacturing process according to the embodiment of FIG. 7.

First, a flat substrate 20 is manufactured (S100).

Then, the in-plane type microneedle array 10 is manufactured (S110). An adhesive is applied to the bottom of the base 12 of the in-plane type microneedle array 10 (S120).

The step S110 of manufacturing the substrate does not have to be in a back and forth relationship with the step S110 of preparing the in-plane type microneedle array and the adhesive application step S120, so that the steps S110 and S120 are before or after the two steps S110 and S120. It may be implemented and may be implemented simultaneously.

Next, the base 12 of the in-plane microneedle array 10 is adhered to one surface of the plate-shaped substrate 20 in close contact with each other (S130). At this time, in the out-of-plane type microneedle array, the base 12 of the in-plane type microneedle array 10 protrudes from the substrate 20. In order to fabricate an out-of-plane microneedle array having a shape as shown in FIG. 1B, a step (S140) of filling the curable material on the substrate 20 to have a thickness equal to the height of the protruding base 12 may be performed. Can be rougher.

9 is a flowchart of a second embodiment of a method for manufacturing an out-of-plane type microneedle array according to the present invention, and FIGS. 10A to 10D are explanatory views illustrating a manufacturing process according to the embodiment of FIG. 9.

First, a flat substrate 20 is manufactured (S200). Then, recesses 21a and 21b are formed on one surface of the substrate 20 (S210). As shown in FIG. 10A, the recesses 21a and 21b may be formed as one groove 21a by digging all of the inner side, leaving only the edge of one surface of the substrate 20, and having a width as shown in FIG. 10B. A plurality of elongated slots 21b larger than the thickness of the base 12 of the internal microneedle array 10 may be formed side by side. Moreover, it is preferable that the depth of recessed part 21a, 21b is more than the height of the base 12 of in-plane type microneedle array.

Meanwhile, the in-plane type microneedle array 10 is manufactured (S220). The step (S220) of manufacturing the in-plane type microneedle array is not in a temporal relationship with the substrate manufacturing step (S200) and the concave forming step (S210), so before or after the two steps (S200, S210) are performed. Of course, it may be performed in the middle or at the same time.

The base 12 of the in-plane microneedle array is accommodated in the recesses 21a and 21b of the substrate 20 (S230). Then, the curable material 90 is filled in the concave portion of the substrate 20 and a post-treatment process is performed to cure the curable material (S340). However, since the size of the in-plane microneedle array 10 is very small, it is difficult to handle. In particular, when the plurality of in-plane microneedle arrays 10 are accommodated in the recesses of the substrate 20, each of the in-plane microneedle arrays is provided. It becomes difficult to arrange the at appropriate intervals. Accordingly, as shown in FIG. 10C, a plastic plate 40 made of a plastic material which is easily changed in shape by external force, such as clay, is manufactured separately (S220a), and the in-plane microneedle array is accommodated in the recess of the substrate (S230). It is preferable to further pass through the step (S220b) of pressing the attachment of the in-plane type microneedle array 10 toward the plastic plate 40 and inserting a portion of the attachment to be buried in the plastic plate 40 before coupling the two together. . As shown in FIG. 9D, the in-plane microneedle array 10 is inserted into the plastic plate 40, and the base of the in-plane microneedle array is accommodated in the recess of the substrate 20 (S230). Through the step (S240) of filling the curable material to the concave portion of the concave, it is easy to handle the in-plane microneedle array during the operation, it is possible to maintain a consistent arrangement between the plurality of in-plane microneedle array. After the curable material is cured, the plastic plate 40 is removed (S250).

11 is a flowchart of a third embodiment of an out-of-plane type microneedle array manufacturing method according to the present invention, and FIG. 12 is an explanatory diagram showing a manufacturing process according to the embodiment of FIG. 11.

First, a flat substrate 20 is manufactured (S300). At this time, the substrate 20 should be made of an elastic material. Thereafter, one side of the substrate 20 is partially cut like a cut, thereby forming a slot 22 (S310). Without the external force, both side walls of the slot 22 are in close contact with each other.

On the other hand, the in-plane type microneedle array 10 is manufactured (S320). The step (S320) of manufacturing the in-plane microneedle array is not in a temporal relationship with the substrate fabrication step (S300) and the slot formation step (S310), so as well as before or after the two steps (S300, S310) are performed. It may be carried out in the middle or at the same time.

The slot 22 is extended in a direction perpendicular to the longitudinal direction to insert the base of the in-plane microneedle array 10 (S330). Since the substrate 20 is made of a resilient material, when the external force is removed, the expanded slot is spontaneously contracted and the in-plane microneedle array 10 is fixed while being inserted into the slot 22. If necessary, it is preferable to further pass the filling step (S340) of the adhesive 22 or the curable material 90 in the free space that can be formed between the slot 22 and the base of the in-plane microneedle array 10.

13 is a flowchart of a fourth embodiment of an out-of-plane type microneedle array manufacturing method according to the present invention, and FIG. 14 is an explanatory diagram showing a manufacturing process according to the embodiment of FIG. 13.

First, a flat substrate 20 is produced (S400). At this time, the substrate 20 is made of a plastic material whose shape is easily changed by external force, such as clay.

Meanwhile, the in-plane type microneedle array 10 is manufactured (S410). The absence of a temporal relationship between the two steps is the same as in the previous embodiments.

Next, the base of the in-plane microneedle array 10 is pressed into the substrate 20 and inserted into the substrate 20 (S420).

On the other hand, the substrate should be flexible in order to be able to adhere to the curved surface of the surface microneedle array. As shown in FIG. 15, it is preferable to form the pleats 23 on one surface of the substrate 20 because the flexibility of the substrate is increased. In order to form the pleats 23 on the substrate of the out-of-plane microneedle array, it is preferable to process the pleats in advance on the surface on which the in-plane microneedle is fixed when fabricating the substrate in each of the above-described embodiments. In addition, in the first or second embodiment, in which the curable material is filled to the same height as the base of the in-plane microneedle array on the substrate, the wrinkled shape is pressed by pressing the stamped curable material before the curable material is cured. Can be formed. The method of forming the pleated profile with a stamp can also be used in the case of the fourth embodiment using a plastic substrate. In other words, before inserting the in-plane microneedle array into the substrate, the wrinkles are formed on the substrate by pressing one surface of the plastic substrate to form a wrinkle on the substrate. In addition, as shown in FIG. 16A, a sheet 60 having a corrugation shape 61 and a hole 62 through which a fine needle penetrates is manufactured, and thus, the substrate 20 of the out-of-plane fine needle array 50 as shown in FIG. 16B. ) Is also possible.

In the case of attaching the out-of-plane microneedle array on the pad to which the drug is applied and using it for drug delivery, the out-of-plane microneedle array as shown in FIG. A hole 20a must be formed through the substrate 20. Such a hole may be formed by a process such as punching after performing a process such as forming the wrinkles described above or by forming an out-of-plane fine needle array without holes.

In all embodiments of the method for manufacturing an out-of-plane type microneedle array according to the present invention described above, the in-plane type microneedle array 10 may be manufactured according to the method for manufacturing an in-plane type microneedle array according to the present invention.

In addition, after making the intaglio mold by making the out-of-plane microneedle array thus manufactured in a circle, injection molding of the polymer, hot embossing of the polymer, or UV nanoimprinting of the monomer using the intaglio mold produced By processing, the out-of-plane microneedle array made of softer material than the ceramic series can be produced in a large amount as in the case of the previous in-plane microneedle array.

An embodiment of the present invention described above and illustrated in the drawings should not be construed as limiting the technical idea of the present invention. The scope of protection of the present invention is limited only by the matters described in the claims, and those skilled in the art can change and change the technical idea of the present invention in various forms. Therefore, such improvements and modifications will fall within the protection scope of the present invention, as will be apparent to those skilled in the art.

The present invention can accurately produce a microneedle of a complex shape, the tip of the fine needle is pointed, the portion close to the substrate is thickened to produce a fine needle with high strength while reducing the pain to the test body, manufacturing cost Compared to the conventional methods, it is inexpensive and enables the manufacture of microneedles that facilitate the injection of drugs into the human body or the extraction of substances in the body without being easily destroyed by wear or impact.

Claims (22)

Manufacturing a base having a flat plate shape, Depositing an electroplating seed layer on an upper surface of the base; Applying a photosensitizer on the electroplating seed layer; Exposing and developing the photosensitive agent with light to expose the electroplating seed layer in a pattern of a predetermined shape; Electroplating the exposed electroplating seed layer; In-plane fine needle manufacturing method comprising the step of separating the plating layer formed by the electroplating. The method of claim 1, In the exposure developing step, the light beam is X-ray, the photosensitive agent is polydimethyl methacrylate, Prior to the step of applying the photosensitive agent, forming an adhesion improving layer on the electroplating seed layer, and in-plane fine micro-method characterized in that it further comprises the step of applying a liquid polydimethyl methacrylate on the surface of the adhesion improving layer How to make a needle. The method of claim 1, In-plane microneedle manufacturing method characterized in that for exposing the light beam inclined with respect to the upper surface of the photosensitive agent layer in the exposure developing step. The method of claim 1, In-plane microneedle array manufacturing method further comprising the step of forming an inclined surface on the upper surface of the base after the step of manufacturing the base. The method of claim 4, wherein forming the inclined surface, Forming an oxide film or a nitride film of a predetermined pattern on an upper surface of the base through a photolithography process; An in-plane type microneedle array manufacturing method comprising etching the base with an anisotropic etching solution. The method of claim 4, wherein forming the inclined surface, Projecting a wall to an upper surface of the base; And filling the curable material in the space between the wall and the upper surface of the base and curing the in-plane microneedle array. The method of claim 1, After the step of manufacturing the base in-plane type microneedle array manufacturing method characterized in that it further comprises the step of forming a narrow ridges protruding on the upper surface of the base. The method of claim 7, wherein forming the fungus, Applying a photosensitizer to the upper surface of the base; In-plane microneedle array manufacturing method comprising the step of removing the photoresist leaving only a narrow band shape by photo-etching. The method of claim 7, wherein forming the fungus, In-plane microneedle array manufacturing method characterized in that the direct etching the base. The method of claim 1, In-plane microneedle array manufacturing method characterized in that it further comprises the step of forming a side groove in the longitudinal direction on one surface of the separated plating layer through a process selected from laser processing or discharge processing. The method according to any one of claims 1 to 10, Manufacturing an intaglio mold by making the separated plating layer into a circle; In-plane microneedle array manufacturing method further comprises the step of injection molding the polymer into the intaglio mold. The method according to any one of claims 1 to 10, Manufacturing an intaglio mold by making the separated plating layer into a circle; The method of manufacturing an in-plane type microneedle array further comprising the step of hot embossing the polymer with the intaglio mold. The method according to any one of claims 1 to 10, Manufacturing an intaglio mold by using the separated plating layer as a circle; In-plane microneedle array manufacturing method further comprising the step of ultraviolet nanoimprinting the monomer with the intaglio mold. Manufacturing a flat substrate; Preparing an in-plane microneedle array; And fixing the in-plane type microneedle array vertically to one surface of the substrate. The method of claim 14, wherein fixing the in-plane microneedle array to a substrate comprises: Applying an adhesive to a bottom surface of the base of the in-plane microneedle array; And attaching the in-plane type microneedle array, to which the adhesive is applied, in close contact with one surface of the substrate. The method of claim 15, The method of claim 1, further comprising the step of curing the curable material by the height protruding from the base surface of the in-plane microneedle array array. The method of claim 14, wherein fixing the in-plane microneedle array to a substrate comprises: Forming a recess on one surface of the substrate; Receiving a base of the in-plane microneedle array in the recess; And filling the curable material with the recess and curing the concave portion. The method of claim 17, Inserting the attachment of the in-plane microneedle array into a plastic plate prior to receiving the base of the in-plane microneedle array in a recess; And receiving the base of the in-plane microneedle array into the concave portion, wherein the base of the in-plane microneedle array inserted into the plastic plate is accommodated in the concave portion. The method of claim 14, In the step of manufacturing the substrate, the substrate is made of an elastic material, Fixing the in-plane type microneedle array to a substrate, Forming a slot by partially cutting one side of the substrate; And extending the slot in a direction perpendicular to the longitudinal direction and inserting a base of the in-plane microneedle array into the slot. The method of claim 19, And a step of curing by pouring a curable material in a free space formed between the slot and the base of the in-plane type microneedle array. The method of claim 14, And forming a wrinkle shape on one surface of the substrate before fixing the in-plane microneedle array to the substrate. The method of claim 14, The method of claim 1, further comprising forming a through hole in the substrate.

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