Exposure apparatus and method for manufacturing needle-shaped structures using exposure

Abstract

The objective is to provide an exposure apparatus that can manufacture micro-order needle-shaped structures with a simple configuration without requiring expensive, specialized parts. [Solution] The exposure apparatus 100 is an exposure apparatus capable of manufacturing needle-shaped structures, and comprises a light source 10 that emits light containing the photosensitive wavelength of a photosensitive material, an optical fiber 20 that guides the light emitted from the light source, an optical fiber holder 30 that holds the optical fiber, a substrate mounting table 40 on which a substrate S on which a liquid photosensitive material R is placed is set, and a vertical movement stage 50 that changes the vertical relative position of the optical fiber holder 30 and the substrate mounting table 40 in order to change the distance between the optical fiber 20 and the substrate S.

Description

[Technical Field]

[0001] The present invention relates to an exposure apparatus and a method for producing a needle-shaped structure using exposure. [Background Art]

[0002] In recent years, in the medical, biotechnology, and electronics fields, demand for micro components and micro devices utilizing microfabrication technology has been rapidly increasing. In particular, in the medical and cosmetic fields, microneedles, which are less invasive to the body and can be used conveniently, have attracted attention, and the market size is expected to reach 9.1 billion US dollars by 2027.

[0003] A microneedle array is formed by arranging fine needles (microneedles) at a predetermined density on a sheet substrate. The microneedles have a conical shape with a root diameter of several tens of micrometers to 500 micrometers, and a length from the tip of several tens of micrometers to several millimeters. The aspect ratio (ratio of diameter to height) is as high as 1:1.5 to 1:3. These microneedles are mainly used by pressing against the human skin, inserting the needles into the surface layer of the skin, and injecting a drug.

[0004] Insertion of microneedles into the skin is from several tens of micrometers to several millimeters from the skin surface, and they can be used without causing pain up to a depth of several hundreds of micrometers. In addition, when separated from the skin, the microneedles are made of a self-dissolving substance that is harmless to the human body, so that even if the microneedles remain in the skin, no adverse effect occurs. For the shape of such microneedles, not only simple conical shapes, but also complex shapes such as truncated conical shapes and stepped shapes for reducing the usage amount of drugs are demanded.

[0005] Microneedles and other micro-order 3D shapes can be manufactured using machining or photolithography. First, a protruding shape is created, and then the hole shape is created by pressing it onto a base material that will serve as the mold (for example, a material that does not affect the human body, such as PTFE, polypropylene, polyethylene, or PDMS (polydimethylsiloxane) if it is a hygroscopic or plastic). Once the mold with the hole shape is complete, the raw material for the needle (for example, gelatin, agarose, maltose, pectin, gellan gum, carrageenan, xanthan gum, alginic acid, or starch) is pressed onto it to manufacture the microneedle.

[0006] On the other hand, among manufacturing methods utilizing photolithography technology, there is a method of single-stroke drawing using a laser. By controlling the power, scanning speed, and number of scans of the laser light source, the amount of light exposure to the resist can be adjusted, and a three-dimensional resist pattern can be obtained. Another method involves fixing a substrate coated with a photosensitive material to an inclined stage and performing oblique exposure while rotating it at a constant speed. By inclining the substrate, the light strikes it from an oblique angle, making it possible to manufacture conical, three-dimensional microstructures that are impossible to create with conventional exposure methods. Another method involves a multi-stage process using multiple masks to layer planar structures. The advantage of this method is that it allows for the production of three-dimensional structures with hollow bodies. Another method involves using a mask (gray mask) in which the light transmittance is controlled by adding shades to the black area of ​​the photomask. This creates a distribution of light intensity, allowing for control over the shape of the pattern transferred to the resist, and enabling the fabrication of three-dimensional microstructures. [Prior art documents] [Patent Documents]

[0007] [Patent Document 1] Special Publication No. 2023-511308 [Non-patent literature]

[0008] [Non-Patent Document 1] Taichi Ibi, et al., Microfluidics and Nanofluidics (2018) 22:69 [Overview of the project] [Problems that the invention aims to solve]

[0009] However, manufacturing by machining requires ultra-high-precision machining equipment and specialized machining techniques and environments. Furthermore, producing complex shapes is technically and costly. Moreover, it is unsuitable for manufacturing intricate structures.

[0010] Furthermore, in manufacturing methods utilizing photolithography technology, creating a conical shape with depth using a single laser stroke requires processing time, which increases costs. Also, in methods where a substrate coated with a photosensitive material is fixed to an inclined stage and exposed at an angle while rotating at a constant speed, it is not possible to create structures with high aspect ratios or complex shapes. In addition, in methods where planar structures are manufactured by stacking multiple masks in a multi-stage process, the cost of masks and the costs associated with the multi-stage process are problematic. Moreover, in methods using gray masks, even a single gray color is expensive, so masks with gradients and other designs result in soaring mask costs. Even with photolithography technology, which excels at microfabrication, manufacturing three-dimensional structures requires specialized equipment and conditions, increasing costs. Furthermore, manufacturing microneedles with high aspect ratios, complex shapes with steps or other features in the conical section, and sharp, pointed tips to improve skin penetration performance has been difficult in terms of both cost and technology.

[0011] This invention has been made in view of the above circumstances, and aims to provide an exposure apparatus that can manufacture micro-order needle-shaped structures with a simple configuration without requiring expensive dedicated parts or equipment, and a method for manufacturing needle-shaped structures using exposure. [Means for solving the problem]

[0012] To solve the above problems, the present invention provides the following means.

[0013] One aspect of the present invention is an exposure apparatus capable of manufacturing a needle-shaped structure, comprising: a light source that emits light containing the photosensitive wavelength of a photosensitive material; an optical fiber that guides the light emitted from the light source; an optical fiber holder that holds the optical fiber; a substrate mounting stage for mounting a substrate on which a liquid photosensitive material is placed; and a vertical movement stage that changes the vertical relative position of the optical fiber holder and the substrate mounting stage in order to change the distance between the optical fiber and the substrate.

[0014] A second aspect of the present invention is the exposure apparatus of the first aspect, wherein the optical fiber holder has a plurality of holding parts that hold a plurality of optical fibers of the same diameter or different diameters.

[0015] A third aspect of the present invention is an exposure apparatus according to aspect 1 or aspect 2, wherein the optical fiber has a diagonally cut end.

[0016] Aspect 4 of the present invention is an exposure apparatus in any one of aspects 1 to 3, comprising a photosensitive material supply mechanism for supplying the photosensitive material onto the substrate.

[0017] Aspect 5 of the present invention is a method for manufacturing a needle-shaped structure using exposure, comprising: a first step of arranging an optical fiber and a photosensitive material such that the tip of the optical fiber is surrounded by a liquid photosensitive material placed on a substrate; a second step of turning on a light source and pulling up the optical fiber away from the substrate while irradiating the photosensitive material with light containing the photosensitive wavelength of the photosensitive material from the tip of the optical fiber; a third step of turning off the light source when the optical fiber has been pulled up to a predetermined height; and a fourth step of removing the uncured photosensitive material.

[0018] Aspect 6 of the present invention is a method for producing a needle-shaped structure using exposure, comprising: a first step of arranging the optical fiber and a liquid photosensitive material such that a tip end of the optical fiber is surrounded within the liquid photosensitive material placed on a base material; a second step of turning on a light source, irradiating the photosensitive material with light including a photosensitive wavelength of the photosensitive material from the tip end of the optical fiber for a predetermined period of time, and then pulling up the optical fiber in a direction away from the base material; a third step of turning on the light source for a predetermined period of time to perform irradiation when the optical fiber is pulled up to a predetermined height; and a fourth step of removing uncured photosensitive material.

[0019] Aspect 7 of the present invention is the method for producing a needle-shaped structure using exposure according to Aspect 5 or Aspect 6, wherein the second step and the third step are repeated a plurality of times.

[0020] Aspect 8 of the present invention is the method for producing a needle-shaped structure using exposure according to any one of Aspects 5 to 7, wherein an optical fiber having a core diameter smaller than that of the optical fiber used in a previous second step is used, the optical fiber is positioned on a structure produced in the previous second step, and then the next second step is performed.

[0021] Aspect 9 of the present invention is the method for producing a needle-shaped structure using exposure according to any one of Aspects 5 to 8, wherein during performing the second step, the diameter of the needle-shaped structure being produced is changed by changing at least one of a pulling-up speed of the optical fiber and the light intensity from the light source.

[0022] Aspect 10 of the present invention is the method for producing a needle-shaped structure using exposure according to Aspect 7, wherein when the second step is repeated two or more times, the diameter of the needle-shaped structure being produced is changed by changing at least one of a pulling-up speed of the optical fiber and the light intensity from the light source in a previous second step.

[0023] Aspect 11 of the present invention is the method for producing a needle-shaped structure using exposure according to any one of Aspects 5 to 10, wherein an optical fiber having an obliquely cut tip is used as said optical fiber.

[0024] Aspect 12 of the present invention is the method for producing a needle-shaped structure using exposure according to any one of Aspects 5 to 11, wherein a plurality of optical fibers having the same diameter or different diameters are used as said optical fiber. Effects of the Invention

[0025] According to the exposure apparatus of the present invention, there can be provided an exposure apparatus that does not require dedicated expensive components or apparatuses, and can produce micro-order needle-shaped structures with a simple configuration. Brief Description of the Drawings

[0026] [Figure 1] It is a principle diagram of the exposure apparatus according to the present invention and the method for producing a needle-shaped structure by exposure. [Figure 2] It is a principle diagram of a method for achieving high aspect ratio of a needle-shaped structure. [Figure 3A] It is a conceptual diagram of a light intensity distribution emitted from an optical fiber. [Figure 3B] It is a conceptual diagram showing the movement of a light intensity distribution caused by a pulling operation of an optical fiber in the Z-axis direction (the direction of changing the distance between said optical fiber and said base material). [Figure 4] It is a schematic cross-sectional view of an example of the exposure apparatus according to the present invention. [Figure 5]The following are schematic cross-sectional diagrams of needle-shaped structures obtained by the exposure apparatus and method for manufacturing needle-shaped structures by exposure according to the present invention: (a) shows a needle-shaped structure in which the vertical cross-section is rectangular and has a cylindrical shape; (b) shows a needle-shaped structure in which the vertical cross-section is trapezoidal and has a diameter that decreases towards the tip (upward direction), but the tip (upward direction) is not pointed and has a frustoconical shape; (c) shows a needle-shaped structure in which the vertical cross-section has a trapezoidal shape on top of a trapezoid and has a stepped diameter that decreases towards the tip (upward direction); and (d) shows a needle-shaped structure in which the vertical cross-section has a triangular shape on top of a trapezoid and has a diameter that decreases towards the tip and has a sharply pointed tip. [Figure 6A] This is an illustrative diagram of the manufacturing process of a needle-shaped structure using a single-mode optical fiber. [Figure 6B] This is an illustrative diagram of the manufacturing process of a needle-shaped structure using multimode optical fibers. [Figure 7A] This is an illustrative diagram of the manufacturing process for a needle-shaped structure using optical fibers with diagonally cut tips. [Figure 7B] This is an illustrative diagram of the manufacturing process of a needle-shaped structure using an optical fiber with a diagonally cut tip, and shows the case where the inclination angle (the angle of inclination from the cross-section of the optical fiber) is larger than that of the optical fiber shown in Figure 7A. [Figure 7C] This is an illustrative diagram of the manufacturing process for a needle-shaped structure using optical fibers, which are covered externally with paint and light-shielding materials. [Figure 8] This is a schematic cross-sectional view of another example of an exposure apparatus according to the present invention. [Figure 9] This is a schematic cross-sectional view of yet another example of an exposure apparatus according to the present invention. [Figure 10] This is an enlarged view of a portion of the principle diagram for the manufacturing method of the needle-shaped structure shown in Figure 1. [Figure 11] This is a flowchart of the method for manufacturing a needle-shaped structure using exposure according to the present invention. [Figure 12] This is a photograph showing the appearance of the exposure apparatus used in the example. [Figure 13] This is a photograph of a needle-shaped structure obtained by varying the exposure time using the method for manufacturing a needle-shaped structure using exposure according to the present invention. [Figure 14] This graph shows the relationship between exposure time and the diameter of the base surface in the method for manufacturing a needle-shaped structure using exposure according to the present invention. [Figure 15] This is a photograph of a needle-shaped structure manufactured using the exposure-based needle-shaped structure manufacturing method of the present invention, under two conditions: an optical fiber pulling distance (scanning distance) of 2 mm and 3 mm. [Figure 16] These are the results of measuring the height, diameter, and aspect ratio of a needle-shaped structure obtained using the method for manufacturing a needle-shaped structure using exposure according to the present invention. [Figure 17] This is a schematic diagram illustrating the manufacturing steps for a two-tiered needle-shaped structure. [Figure 18] This is a photograph of a two-stage needle-shaped structure obtained using the method for manufacturing a needle-shaped structure using exposure according to the present invention. [Figure 19] This is a conceptual diagram of a needle-shaped structure obtained using an optical fiber with a diagonally cut tip. [Figure 20] This is a photograph of an optical fiber with a tip cut at a 30-degree angle and the resulting needle-like structure. [Modes for carrying out the invention]

[0027] The present invention will be described in detail below, with reference to the drawings as appropriate. The drawings used in the following description may be enlarged for convenience to clearly illustrate the features, and the dimensional ratios of each component may differ from those of the actual components. The dimensions and other specifications exemplified in the following description are examples only, and the present invention is not limited to them. It is possible to modify and implement the invention as appropriate within the scope of achieving its effects. Unless otherwise specified, the configuration described in one embodiment may be applied to other embodiments.

[0028] Figures 1 to 3 show the principle diagrams of the exposure apparatus and the method for manufacturing a needle-shaped structure using exposure according to the present invention. As shown in Figure 1, in the method for manufacturing a needle-shaped structure using exposure according to the present invention, the tip of an optical fiber connected to a light source with a photosensitive wavelength, such as UV light, is immersed in a liquid photosensitive substance dropped onto a substrate, and the portion exposed to the UV light emitted from the optical fiber hardens. The unhardened photosensitive substance is removed by immersing the substrate in a solvent, and a needle-shaped structure is formed.

[0029] In the method for manufacturing a needle-shaped structure using exposure according to the present invention, a method for increasing the aspect ratio of the needle-shaped structure will be explained with reference to Figure 2. With the light source turned on, the optical fiber is pulled up in the Z-axis direction (away from the substrate). Since the tip of the optical fiber is inside the photosensitive material, liquid photosensitive material is continuously supplied between the substrate and the tip of the optical fiber. The supplied liquid photosensitive material hardens with UV light and is layered, allowing for the manufacture of a needle-like structure as a three-dimensional structure with a high aspect ratio.

[0030] Figure 3A shows the light intensity distribution emitted from the optical fiber. The light intensity distribution is close to a Gaussian distribution, with the light intensity being stronger near the center of the optical fiber.

[0031] Figure 3B conceptually illustrates the shift in the optical intensity distribution due to the pulling motion of the optical fiber in the Z-axis direction. As the optical fiber is pulled up in the Z-axis direction, the light intensity distribution, shown by the dashed line in Figure 3B, moves upward. The hardened area gradually expands as the light intensity distribution moves, but because the light intensity at the tail of the Gaussian distribution is weak, the light intensity distribution superimposed upwards becomes shown by the solid line, and the hardened area does not expand as much. As a result, a high aspect ratio three-dimensional structure (needle-shaped structure) is formed.

[0032] Non-patent document 1 describes a technique for manufacturing a three-dimensional structure by immersing the tip of an optical fiber in a liquid photosensitive material and irradiating it with UV light emitted from the optical fiber. However, it does not describe or suggest any method for increasing the aspect ratio of the three-dimensional structure as described above.

[0033] (Exposure equipment) Figure 4 shows a schematic cross-sectional view of an example of an exposure apparatus according to the present invention. The exposure apparatus 100 shown in Figure 4 is an exposure apparatus capable of manufacturing needle-shaped structures and comprises a light source 10 that emits light containing the photosensitive wavelength of a photosensitive material, an optical fiber 20 that guides the light emitted from the light source, an optical fiber holder 30 that holds the optical fiber, a substrate mounting stand 40 on which a substrate S on which a liquid photosensitive material R is placed is installed, a vertical movement stage 50 that changes the vertical relative position of the optical fiber holder 30 and the substrate mounting stand 40 in order to change the distance between the optical fiber 20 and the substrate S, and a horizontal movement stage 60 that changes the horizontal relative position of the optical fiber 20 and the substrate mounting stand 40. The exposure apparatus 100 shown in Figure 4 is equipped with a horizontal moving stage 60, but a configuration without a horizontal moving stage 60 is also possible. For example, to manufacture a single needle-shaped structure rather than an array or matrix of needle-shaped structures, the horizontal moving stage 60 may not be necessary.

[0034] In Figure 4, the exposure apparatus 100 is an example of an exposure apparatus according to the present invention. For example, the substrate mounting table 40 and the horizontal moving stage 60 may be an integrated component, in which case the upper surface of the horizontal moving stage may also serve as the substrate mounting table. Furthermore, the vertical moving stage 50 and the horizontal moving stage 60 may be a 3-axis stage that can move in the XYZ directions and combines the functions of the vertical moving stage 50 and the horizontal moving stage 60. Furthermore, the vertically moving stage 50 and the horizontally moving stage 60 may move automatically or manually, or their movement may be controlled by a control device.

[0035] Furthermore, the optical fiber holder 30 shown in Figure 4 has a configuration comprising a holding arm (holding part) 30a having a hole into which an optical fiber is inserted, and a holding base 30b located on the vertical movement stage 50 side to which the holding arm 30a is fixed, but is not limited to this configuration. The holding arm 30a may have multiple holes for inserting multiple optical fibers, for example, it may be an array-shaped holding arm that can arrange optical fibers in a single row, or a holding arm that can hold multiple rows vertically and horizontally in a matrix shape, and the holding arm 30a may be detachable from the holding base 30b. The optical fiber may be detachable from the holding arm 30a and can be changed during exposure, or the optical fiber may be fixed to the holding arm 30a and the holding arm 30a may be replaced with a holding arm 30a to which another optical fiber is fixed during exposure.

[0036] Furthermore, the exposure apparatus according to the present invention may include a photosensitive substance supply mechanism for supplying a photosensitive substance R onto a substrate S.

[0037] Here, "needle-shaped structure" refers to a structure with a large aspect ratio, including structures with a cone-shaped tip. Typical shapes of needle-shaped structures are shown in Figures 5(a) to (d). Figures 5(a) to (d) are schematic cross-sectional diagrams showing the shape of the cross-section when a needle-shaped structure is cut in the height direction (up and down direction). Note that the shapes shown in Figures 5(a) to (d) are approximate, and the actual manufactured shapes will vary. There are no restrictions on the size of the needle-like structures, but they can be in the range of a few micrometers to a few millimeters. Furthermore, by manufacturing the needle-shaped structures while moving the substrate S with the horizontal moving stage 60, it is possible to manufacture arrays in which needle-shaped structures are arranged in a single vertical line, or matrices in which multiple needle-shaped structures are arranged vertically and horizontally.

[0038] Figure 5(a) shows a needle-like structure with a rectangular cross-section in the vertical direction, and can illustrate a needle-like structure having a cylindrical shape. Figure 5(b) shows a needle-like structure with a trapezoidal cross-section in the vertical direction. The diameter decreases towards the tip, but the tip is not pointed, and it can be used as an example of a frustoconical needle-like structure. Figure 5(c) shows a needle-like structure with a stepped shape, where the vertical cross-section has a trapezoidal shape on top of another trapezoidal shape, and the tip (upward direction) has a smaller diameter. This illustrates a needle-like structure with a stepped truncated cone shape. Figure 5(d) illustrates a needle-shaped structure having a conical portion at the tip of the frustoconical needle-shaped structure shown in Figure 5(b). In this needle-shaped structure, the vertical cross-section has a trapezoidal shape with a triangular shape on top, and the diameter decreases towards the tip, and the tip is sharply pointed.

[0039] The light source 10 can be a known light source that includes the photosensitive wavelength of a photosensitive material, such as a laser, laser diode (LD), light-emitting diode (LED), or lamp. Furthermore, there may be one or more light sources, and the configuration may involve connecting one light source to multiple optical fibers, or connecting multiple light sources to multiple optical fibers. For example, multiple light sources can include an LED matrix. An LED matrix is ​​a configuration where light sources are arranged in a matrix, and the light intensity of each individual light source can be changed by a control device.

[0040] Optical fiber 20 can be any known optical fiber that guides light, such as single-mode or multi-mode fiber. For example, the material can be plastic, glass, liquid, etc.

[0041] For the optical fiber 20, a core diameter matching the diameter of the needle-shaped structure to be manufactured can be used. For single-mode optical fibers used for communications, etc., the core diameter can range from a few micrometers to several hundred micrometers or a few millimeters, while for multi-mode optical fibers used for image transmission, etc., it can range from tens of micrometers to several hundred micrometers or a few millimeters. By using optical fibers with a small diameter, it is possible to manufacture small-diameter three-dimensional structures. Conversely, by using optical fibers with a large diameter, it is possible to manufacture large-diameter three-dimensional structures.

[0042] As for the optical fiber 20, one that matches the shape of the needle-shaped structure to be manufactured can be used. The refractive index of the optical fiber is related to the incident and exit angles of light, and in particular, the exit angle of light affects the shape of the structure to be manufactured. As shown in Figure 6A, single-mode optical fibers have a small difference in the refractive index of the core and cladding materials, so the exit angle is limited, making them suitable for manufacturing needle-shaped structures that are nearly vertical. As shown in Figure 6B, multimode optical fibers have a large refractive index of the core and cladding materials, so they can emit light at various angles. For this reason, the angle of the emitted light is broadened, making them suitable for manufacturing conical needle-shaped structures.

[0043] As shown in Figures 7A and 7B, the optical fiber 20 may have a tip that is cut at an angle. The angle of inclination can be set to suit the tip shape of the needle-like structure to be manufactured, as shown in Figures 7A and 7B. As shown in Figure 7B, the larger the angle of inclination of the optical fiber relative to the cross-section, the more acute the tip shape becomes, and the smaller the angle, the more obtuse the angle becomes. It is desirable to cut the tip of the optical fiber at an angle with a sharp object such as a cutting tool, and then polish the cut surface.

[0044] Furthermore, the tip of the optical fiber having a diagonally cut end should preferably be covered with paint (for example, black paint) or a light-shielding material, as indicated by reference numeral 21 in Figure 7C. This has the effect of preventing light reflected from the diagonally cut portion from leaking out and destabilizing the shape of the needle-like structure.

[0045] Multiple optical fibers 20 can be used. The multiple optical fibers may have different core diameters or tip shapes. The exposure apparatus 101 shown in Figure 8 is equipped with multiple optical fibers (20-1, 20-2, 20-3). Having multiple optical fibers allows for the production of array or matrix-arranged needle-like structures in a single exposure process. While Figure 8 illustrates the case with three optical fibers, there is no limit to the number of fibers. Furthermore, by installing multiple optical fibers with different core diameters and tip shapes, and with diagonally cut tips, it is possible to efficiently manufacture needle-shaped structures of different shapes without having to replace the optical fibers.

[0046] Any known photosensitive material can be used as the photosensitive material. Examples include UV-curable resins, resins for stereolithography 3D printers, biocompatible resins (such as those from Okamoto Chemical Industry), and SU-8 (Nippon Kayaku). While transparent photosensitive materials are preferable, opaque materials are also acceptable. Opaque materials are effective for manufacturing thin, nearly vertical needle-like structures because they prevent light from spreading.

[0047] The optical fiber holder 30 may have a plurality of holding arms 30a that can hold a plurality of optical fibers horizontally spaced apart from each other.

[0048] The photosensitive material R may be continuously supplied to the substrate S from a photosensitive material supply mechanism (not shown), or, as in the exposure apparatus 102 shown in Figure 9, the substrate S may be placed in a tank 70 containing the photosensitive material.

[0049] (Method for manufacturing needle-shaped structures using exposure) The method for manufacturing a needle-shaped structure using exposure according to the present invention will be explained with reference to Figures 4, 10, and 11. Figure 10 is an enlarged view of a portion of the principle diagram of the method for manufacturing a needle-shaped structure shown in Figure 1. Figure 11 is a flowchart of the method for manufacturing a needle-shaped structure using exposure.

[0050] The method for manufacturing a needle-shaped structure using exposure according to the present invention comprises at least the following first (S1) to fourth (S4) steps. In the first stage (S1), the optical fiber 20 and the photosensitive material R are positioned such that the tip 20a of the optical fiber 20 is surrounded within the liquid photosensitive material R placed on the substrate S. In the second stage (S2), the light source 10 is turned on, and light containing the photosensitive wavelength of the photosensitive material R (UV light) is irradiated onto the photosensitive material R from the tip 20a of the optical fiber 20, while the optical fiber 20 is pulled up in the direction away from the substrate S (Z direction). In the third stage (S3), the light source 10 is turned off when the optical fiber 20 is raised to a predetermined height. This causes the tip of the optical fiber and the tip of the needle-shaped structure to peel off cleanly without connecting. The fourth step (S4) involves removing the uncured photosensitive material.

[0051] The second stage (S2) and the third stage (S3) may be repeated multiple times. By repeating the process multiple times, it is possible to manufacture needle-shaped structures with a large aspect ratio.

[0052] When the second stage (S2) and the third stage (S3) are repeated multiple times, the next second stage (S2) can be performed using an optical fiber with a core diameter smaller than that of the optical fiber used in the previous second stage (S2). This makes it possible to manufacture needle-shaped structures having a multi-tiered structure of two or more tiers.

[0053] During the execution of the second stage (S2), the diameter of the needle-shaped structure being manufactured can be changed by changing at least one of the pulling speed of the optical fiber 20 and the light intensity from the light source 10. Increasing the pulling speed yields a needle-shaped structure with a small diameter, while decreasing the pulling speed yields a needle-shaped structure with a large diameter. Furthermore, by reducing the light intensity, needle-shaped structures with a small diameter can be obtained, while by increasing the light intensity, needle-shaped structures with a large diameter can be obtained.

[0054] When the second stage (S2) is repeated two or more times, the diameter of the needle-shaped structure being manufactured can be partially changed by changing at least one of the pulling speed of the optical fiber 20 and the light intensity from the light source 10 in the previous second stage (S2).

[0055] As the optical fiber 20, an optical fiber with a diagonally cut tip can be used. By using an optical fiber with a diagonally cut tip, a needle-shaped structure with a sharp tip can be obtained. The larger the angle of the diagonal inclination, the more acute the tip shape of the needle-shaped structure to be manufactured will be, and the smaller the angle, the more obtuse it will be.

[0056] Multiple optical fibers can be used as the optical fiber 20. By having multiple optical fibers, needle-shaped structures in array or matrix arrangements can be manufactured in a single exposure process. Furthermore, by installing multiple optical fibers with diagonally cut tips and different core diameters and tip shapes, needle-shaped structures of different shapes can be efficiently manufactured without changing the optical fibers.

[0057] In the fourth stage (S4), the substrate can be immersed in a solvent to remove any uncured photosensitive material.

[0058] In the second stage (S2'), the light source 10 is turned on, and light containing the photosensitive wavelength of the photosensitive material R (UV light) is irradiated onto the photosensitive material R from the tip 20a of the optical fiber 20 for a certain period of time, after which the optical fiber 20 is pulled up in the direction away from the substrate S (Z direction).

[0059] In the third stage (S3'), the light source 10 is turned on for a certain period of time when the optical fiber 20 is raised to a predetermined height. This transfers the tip shape of the optical fiber to the tip shape of the needle-shaped structure. After that, the light source is turned off.

[0060] The resulting needle-like structure may be subjected to secondary processing. For example, when obtaining a needle-shaped structure with a pointed tip, such as a microneedle, if the tip of the manufactured needle-shaped structure does not have the desired sharpness, the desired sharpness may be obtained by mechanical processing. Additionally, if you want the microneedles to be hollow to ensure a liquid transport path, you can make a hole in the center with a needle-like object.

[0061] The structure in which needle-shaped structures are arranged on a substrate can be manufactured by inverting the mold and pouring in PDMS (silicone) or metal materials, or by plating. Using this mold, needle-shaped structures can be manufactured by pouring in biocompatible resins or silicones. [Examples]

[0062] The present invention will be described below with reference to examples, but the present invention is not limited to the following examples.

[0063] Figure 12 shows the appearance of the exposure apparatus used in the example. The exposure apparatus measures 170mm wide, 170mm deep, and approximately 190mm high. Motorized stages for the X-axis (horizontal) and Z-axis (vertical) are placed on an aluminum plate. A holder for holding optical fibers is attached to the Z-axis stage. A UV-LED irradiator (Omron Corporation, model number ZUV-C10, light source wavelength 365nm) is used as the light source (not shown). A multimode optical fiber (Mitsubishi Rayon, Esca CK-10) with a diameter of 250μm and a core diameter of 235μm was used as the optical fiber. A commercially available UV-LED resin (Padico Corporation, product number 403245) that shows high sensitivity to the wavelength of the light source was used as the photosensitive material (photocurable resin), and a silicon wafer with high flatness was used as the substrate.

[0064] The distance between the substrate and the end face of the optical fiber is fixed at 1 mm, and the light intensity is set to 10% (120 mW / cm²) of the light source. 2The needle-like structures were fabricated by fixing them to a surface and varying the exposure time. Figure 13 shows photographs of the needle-like structures obtained by varying the exposure time. The obtained needle-like structures are frustoconical in shape, and the shape itself does not change significantly, but it can be seen that the shape expands and becomes larger as the exposure time increases.

[0065] Figure 14 shows the relationship between exposure time and the diameter of the base. Figure 14 shows that the diameter of the base expands as the exposure time increases. However, the rate of increase in the diameter of the base gradually decreases as the exposure time increases, suggesting that there is a certain threshold for the diameter of the base. This is thought to be due to the intensity distribution of the light emitted from the optical fiber.

[0066] Figure 15 shows photographs of needle-shaped structures manufactured under two conditions: optical fiber pull-up distance (scanning distance) of 2 mm and 3 mm. The light intensity was fixed at 10% of the light source setting, and the pulling speed was reduced to 20 μm / s up to half the scanning distance, and then to 10 μm / s thereafter. The reason for reducing the speed was that when the experiment was conducted with the pulling speed fixed at 20 μm / s, the curing reaction did not keep pace with the pulling speed.

[0067] It can be seen that a needle-shaped structure with a high aspect ratio is obtained by pulling up the optical fiber (scanning in the Z-axis direction). It can be seen that there are differences in the height of the needle-like structure depending on the pulling distance of the optical fiber. Table 1 shows the results of measurements of the height, diameter, and aspect ratio of the needle-like structure. From the measurement results shown in Figure 16, it can be seen that both the height and diameter increase with increasing pulling distance. Although both the height and diameter increase, there are differences in the amount of increase. The height changes significantly with the pulling distance, but the diameter of the structure does not change as much with respect to the pulling distance, remaining at about 2 to 2.5 times the diameter of the optical fiber. This shows that the longer the elevation distance, the higher the aspect ratio can be achieved.

[0068] We manufactured a needle-like structure with a two-tiered design. The tip shape is an important factor that affects the puncture performance of the microneedle. Figure 17 shows a schematic diagram illustrating the manufacturing steps for a two-tiered needle-shaped structure. The two-tiered needle-shaped structure can be manufactured by using an optical fiber with a large core diameter for the first tier and an optical fiber with a small core diameter for the second tier above it.

[0069] Because precise visual alignment was difficult, a frustoconical structure, as shown in Figure 13, was formed on top of a pre-fabricated large structure. A photograph of the resulting two-tiered needle-like structure is shown in Figure 18. This demonstrated that it is possible to reduce the diameter of the tip.

[0070] Next, we will show the results using an optical fiber with a diagonally cut tip. Figure 19 shows a conceptual diagram of a needle-shaped structure obtained using an optical fiber with a diagonally cut tip. UV light emitted from an optical fiber with a diagonally cut tip is irradiated in such a way that it has a light intensity distribution shape as shown in Figure 19. The resulting needle-shaped structure has a pointed tip that reflects this light intensity distribution shape of the UV light.

[0071] As optical fibers with diagonally cut ends, we used optical fibers cut at a 30° angle to the end face. The light intensity was fixed at the light source setting, and a needle-shaped structure was fabricated by exposing the optical fiber 1 mm away from the substrate for a duration of 100 s.

[0072] Figure 20 shows the optical fiber actually used and a photograph of the resulting needle-shaped structure. Figure 20 shows that we were able to manufacture a needle-like structure with a tip that was as sharp as the tip of an optical fiber. [Explanation of symbols]

[0073] 10 light source 20 Optical Fibers 30 Fiber Optic Holders 40 Base material installation stand 50 Stages with vertical movement 60 Horizontal movement stage 100 Exposure equipment

Claims

1. An exposure apparatus capable of manufacturing needle-shaped structures, A light source that emits light containing the photosensitive wavelength of a photosensitive material, An optical fiber that guides the light emitted from the aforementioned light source, An optical fiber holder for holding the optical fiber, A substrate mounting stand for which a substrate on which a liquid photosensitive substance is placed is installed, An exposure apparatus comprising a vertical movement stage that changes the vertical relative position of the optical fiber holder and the substrate mounting base in order to change the distance between the optical fiber and the substrate.

2. The exposure apparatus according to claim 1, wherein the optical fiber holder has a plurality of holding portions for holding a plurality of optical fibers of the same diameter or different diameters.

3. The exposure apparatus according to claim 1, wherein the optical fiber has a diagonally cut end.

4. The exposure apparatus according to claim 1, further comprising a photosensitive material supply mechanism for supplying the photosensitive material onto the substrate.

5. A method for manufacturing a needle-shaped structure using exposure, The first step is to arrange the optical fiber and the photosensitive material such that the tip of the optical fiber is surrounded within a liquid photosensitive material placed on the substrate, The second step involves turning on the light source and irradiating the photosensitive material with light containing the photosensitive wavelength of the photosensitive material from the tip of the optical fiber, while pulling the optical fiber away from the substrate. A third step involves turning off the light source when the optical fiber is raised to a predetermined height, A method for manufacturing a needle-shaped structure using exposure, comprising a fourth step of removing uncured photosensitive material.

6. A method for manufacturing a needle-shaped structure using exposure, The first step is to arrange the optical fiber and the photosensitive material such that the tip of the optical fiber is surrounded within a liquid photosensitive material placed on the substrate, The second step involves turning on the light source and irradiating the photosensitive material with light containing the photosensitive wavelength from the tip of the optical fiber for a certain period of time, after which the optical fiber is pulled up in a direction away from the substrate. The third step involves turning on the light source and illuminating the optical fiber for a certain period of time when the optical fiber is raised to a predetermined height, A method for manufacturing a needle-shaped structure using exposure, comprising a fourth step of removing uncured photosensitive material.

7. A method for manufacturing a needle-shaped structure using exposure according to claim 5 or 6, wherein the second and third steps are repeated multiple times.

8. A method for manufacturing a needle-shaped structure using exposure according to claim 7, wherein an optical fiber with a core diameter smaller than that of the optical fiber used in the preceding second stage is used, the optical fiber is positioned on the structure manufactured in the preceding second stage, and then the next second stage is carried out.

9. A method for manufacturing a needle-shaped structure using exposure according to claim 5 or 6, wherein the diameter of the needle-shaped structure being manufactured is changed by changing at least one of the speed at which the optical fiber is pulled up and the light intensity from the light source during the execution of the second step.

10. A method for manufacturing a needle-shaped structure using exposure according to claim 7, wherein, when the second step is repeated two or more times, the diameter of the needle-shaped structure being manufactured is changed in the first second step by changing at least one of the speed at which the optical fiber is pulled up and the light intensity from the light source.

11. A method for manufacturing a needle-shaped structure using exposure according to claim 5 or 6, wherein the optical fiber used is an optical fiber having a diagonally cut tip.

12. A method for manufacturing a needle-shaped structure using exposure according to claim 5 or 6, wherein a plurality of optical fibers having the same or different diameters are used as the optical fibers.

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