JP2008029386A - Method for manufacturing plate for needle-like body and method for manufacturing needle-like body - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for manufacturing a plate which is suitable for the large-scale production for manufacturing a fine array-like needle-like body which has a sharp distal end part and a thick base part and shows an excellent strength and a method for manufacturing the biocompatible needle-like body by using the plate. <P>SOLUTION: The method for manufacturing the plate for forming the needle-like bodies integrally molded in an array shape on a substrate 10 includes (1) the process of performing a first process of forming a mask 11 having opening parts at positions where hole shapes corresponding to a plurality of needle-like bodies are formed and of forming the hole shapes which correspond to main bodies of the needle-like bodies, are vertically cut deep, and have the shape of a rectangular solid by using a dry etching method and (2) the process of performing a second process of peeling the mask 11 and forming the distal end part of the needle-like body and a slanting shape at a site corresponding to the base part by crystal anisotropic etching. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a method for producing a needle-shaped plate and a method for producing a needle-like body for producing fine needles for use in medicine and drug discovery such as a drug delivery system (hereinafter referred to as DDS).

  In recent years, in the field of medicine and drug discovery, the development of fine needles as painless needles without pain has been promoted.

  There are two types of fine needles, one that is used alone and the other that is used in an array.

  Conventionally, many fine needles are made of silicon. As one of the manufacturing methods, as disclosed in Patent Document 1, after providing a mask on a silicon substrate, isotropic etching or crystal anisotropic etching is performed to form a needle tip to some extent, After anisotropic etching is performed to form the needle body, the deposited layer deposited on the side surface is removed, and further, gradient etching is performed to sharpen the tip.

However, in this method, there is a problem in that the mask is collapsed by thinning the portion immediately below the mask, and the yield is deteriorated. Further, in this method, gradient etching using an HNO ₃ / HF / CH ₃ COOH / H ₂ O solution is performed as a method of sharpening the tip by gradient etching, but when the tip of the needle is formed, the tip is formed. Since the thin tip portion of the film is preferentially etched, the sharpness of the tip portion cannot be obtained.

  In addition, as a painless needle material used in DDS, if a silicon needle is used as it is, there will be a disadvantage that the solid silicon needle will remain in the body when it is broken in the body, so transfer from the original plate. Repeatedly, it will be necessary to produce a final product of a biocompatible material.

  At this time, if the silicon needle is used as the original plate, at least two transfer steps are required until the final product, which deteriorates the yield in mass production.

In the fields of medicine and drug discovery, the influence on the human body cannot be ignored. For this reason, a needle-like body using a material that has a low impact on the human body is desired for use in the human body. There has been reported an example in which a fine needle-like body using polylactic acid or the like is formed as a material having such a low impact on the human body (Patent Document 2).
Japanese Patent Laying-Open No. 2005-199392 (see paragraph number 0004) JP 2005-21677 A

  Therefore, the technical problem to be solved by the present invention is a plate mold for manufacturing a fine array of needles suitable for mass production, sharp at the tip and thick at the root, and having high strength. It is to provide a method for producing a needle-shaped body that is compatible with a living body, using a plate mold.

  The present invention has been made in view of the above technical problem, and provides a method for producing a needle-shaped plate and a method for producing a needle-like body having the following configuration.

The invention according to claim 1 is a method of manufacturing a plate mold for forming a needle-like body, which can be integrally formed into an array.
(1) A mask having openings corresponding to a plurality of needles corresponding to a plurality of needle-like bodies was formed, and was deeply dug vertically corresponding to the main body of the needle-like body using a dry etching method. Applying a first process for forming a rectangular parallelepiped hole mold;
(2) peeling the mask and performing a second process of forming an inclined shape at a portion corresponding to the tip and root of the acicular body by crystal anisotropic etching;
It is the said manufacturing method characterized by having.
The invention according to claim 2 is the manufacturing method according to claim 1, wherein the material of the plate is silicon.
A third aspect of the present invention is the manufacturing method according to the second aspect, wherein a side surface of the rectangular parallelepiped hole mold that is deeply dug is a silicon (110) surface.
According to a fourth aspect of the present invention, in the second or third aspect, the inclined shape corresponding to the tip of the needle-like body has a hole shape constituted by a (111) surface of silicon. It is a manufacturing method of description.
The invention according to claim 5 has a hole shape in which an inclined shape corresponding to a root portion of the needle-like body is constituted by a (311) plane of silicon. It is the manufacturing method in any one.
According to a sixth aspect of the present invention, a needle-like body using a biocompatible resin is formed using the plate mold produced by the production method according to any one of the first to fifth aspects. It is a manufacturing method of a body.

  According to the first aspect of the present invention, a plate mold for manufacturing a fine array-like needle-shaped body that is suitable for mass production, has a sharp tip, a thick root, and high strength, and the plate It is possible to provide a needle-like body that is manufactured by using and compatible with a living body.

  According to the invention described in claim 2, since the material of the plate is made of silicon, it is excellent in workability and wear resistance and is suitable for fine processing, and a silicon substrate (silicon wafer) is used for a semiconductor process or the like. It is easy to obtain and inexpensive. Further, since the etching rate of silicon differs greatly depending on the plane orientation with respect to the crystal anisotropic etching process, it is possible to easily form an inclined tapered surface that becomes the shape of the tip of the needle-like body.

  Further, as in the invention described in claim 3, when the side surface of the rectangular parallelepiped-shaped hole shape is a silicon (110) surface and crystal anisotropic etching is performed, the crystal anisotropic etching process is performed. As in the invention, the inclined shape corresponding to the tip of the needle-like body is constituted by the (111) plane of silicon. In this case, the (111) plane having a low etching rate is formed at an angle of 35.3 degrees with respect to the (110) plane. This angle is an angle inevitably determined by the physical properties of silicon. Thereby, the angle θ of the tip of the needle-like body is 70.6 degrees. Further, when the inclined shape corresponding to the root portion of the needle-like body is constituted by the (311) plane of silicon as in the invention described in claim 5, the needle-like body is taken out from the plate mold. This surface is advantageous because it is easy to come off, and this surface is the base of the needle-like body, which increases the strength of the needle-like body.

  Further, according to the invention described in claim 6, since the plate mold manufactured by the manufacturing method of any one of claims 1 to 5 is used, the needle-shaped body using the biocompatible resin is productive. It can be manufactured well and is particularly advantageous for materials for painless needles used in DDS.

  Hereinafter, a plate manufacturing method for forming a fine needle-like body that can be integrally formed into an array according to the present invention will be described in detail in the order of steps with reference to FIGS.

(1) Patterning a resist mask on a silicon wafer (Figures 1 (a) to (c))
First, as shown in FIG. 1A, a silicon wafer 10 is prepared, and as shown in FIGS. 1B to 1C, a resist mask 11 is applied to the front surface of the silicon wafer 10, Patterning into a predetermined shape. For example, as shown in FIG. 2, the patterning is preferably performed so as to be a mask having openings 11a at locations where hole shapes corresponding to a plurality of needle-like bodies are to be formed.
The opening 11a has a rectangular shape as shown in FIG. 2 and is formed on the (100) plane of the silicon wafer 10. At this time, the opening 11a is arranged such that any one side of the square in the opening 11a is parallel to the (110) plane of the silicon wafer 10.
For the resist, for example, a positive resist is used. For example, a spin coater is used for resist coating. An aligner is used for exposure.

(2) Process of deep digging using a resist mask (Figure 1 (d))
Next, dry etching is performed from the surface on the front side of the silicon wafer 10 and deep digging is performed vertically to a predetermined depth. As shown in FIG. 1D, hole shapes corresponding to a plurality of needle-like bodies are formed. Form. An ICP-RIE (reactive ion etching using inductively coupled plasma) apparatus is used for dry etching. Due to the arrangement of the openings 11a described above, the side surface 10b inside the hole mold becomes the (110) plane when deep digging is performed.

(3) Process to remove resist mask (Figure 1 (e))
Next, as shown in FIG. 1E, the resist mask 11 formed on the silicon wafer 10 is removed. The resist mask 11 is removed by, for example, ashing using oxygen plasma.

(4) Step of forming an acicular shape by performing crystal anisotropic etching (FIG. 1 (f))
Next, as shown in FIG. 1F, crystal anisotropic etching is performed on the silicon wafer 10 that has been deep-digged. Crystal anisotropic etching performs so-called wet etching, for example, by using a tetramethylammonium hydroxide (TMAH) solution and immersing the silicon wafer 10 that has been deep-digged for a predetermined time, so that etching of the bottom surface proceeds. Process until it runs out. As described above, a silicon wafer 10 having a (100) surface is used, and etching proceeds so that the (111) surface 13 on the bottom surface becomes the tip end slope of the needle-like body by anisotropic etching. . The (111) plane appears from the boundary between the four sides and bottom of the hole shape formed by deep drilling, and the etching stops when they intersect.

  Further, in the hole-shaped inlet portion, the etching proceeds so that the (311) plane 12 appears on the (100) plane side. For this reason, a forward taper shape is obtained from the base part of the acicular body to the part to be the main body part.

  Such a reverse taper shape is advantageous in that it can be easily removed even when the needle-shaped body is actually taken out from the plate mold, and has an advantage that the strength of the manufactured needle-shaped body itself is increased.

(5) Step of forming a needle-like body using a biocompatible resin When forming the needle-like body using a biocompatible resin using the above-mentioned plate mold, an imprint method, a hot embossing method, an injection molding The needle-shaped body is duplicated by the method of casting or casting. The material of the replicated product is not particularly limited, but a needle-like body applicable to a living body can be formed by using a biocompatible material such as dextran, polylactic acid, or silicone.

  EXAMPLES Hereinafter, although an Example demonstrates this invention further, this invention is not restrict | limited to the following example.

Example 1
A single crystal silicon wafer 10 having a (100) plane and a thickness of 525 μm was prepared.

  Next, a resist mask patterning process for deep digging was performed on the silicon wafer 10 in the following manner. That is, on the front side (100) of the silicon wafer 10, the resist mask 11 is formed by a well-known spin coating and developing method so that the holes 11a corresponding to a plurality of needle-like bodies are to be formed as the openings 11a. Then, a resist mask was formed. The resist mask had a thickness of 14 μm, and a positive resist developer was used as the developer.

  As shown in FIG. 1 (d), the silicon wafer with resist 10 manufactured in this way is subjected to a vertical deep digging process using ICP-RIE to form a rectangular parallelepiped shape corresponding to a plurality of needle-like bodies. A hole mold was formed.

  The depth in the vertical direction with respect to the hole-shaped silicon wafer 10 was set to 200 μm.

  Next, the resist mask 11 was removed by performing ashing using oxygen plasma for 30 minutes.

  Next, by performing anisotropic crystal etching on the silicon wafer 10 from which the resist mask 11 has been removed, an inclined shape corresponding to the tip and root portions of the needle-like body is created as shown in FIG. did.

  As the etching solution, 6 L of TMAH solution diluted to 12.5% was prepared.

  The TMAH solution diluted to 12.5% was heated to 80 ° C., and the silicon wafer 10 subjected to deep digging was immersed therein for 40 minutes, and then rinse treatment was performed for immersion in ultrapure water for 20 minutes.

  As shown in FIG. 3A, the front surface 10a and the bottom surface of the silicon wafer 10 are the (100) plane, and the side surface 10b inside the hole mold is the (110) plane. When etching with a TMAH solution, as shown in FIGS. 3B and 3C, a (111) surface 13 whose etching rate is slower than the boundary between the bottom surface and the side surface of the hole mold appears on the surface, and (111) When the surfaces 13 are in contact with each other, the etching rate is rapidly reduced and the shape is maintained. The inverted pyramid portion thus formed has a shape corresponding to the tip of the needle-like body. In this case, the angle θ of the tip of the needle-like body is 70.6 degrees. A metastable (311) surface 12 appears on the surface at the boundary between the side surface and the surface, and forms a shape corresponding to the base of the needle-like body.

  When transfer was performed using the plate thus produced, needles 14 as shown in FIG. 4 were formed in an array.

Example 2
The needle-shaped body was duplicated by the imprint method using the plate mold. Here, polylactic acid, which is a biocompatible material, was used. Thereby, the acicular body which consists of polylactic acid was able to be formed in the form integrally molded by the array form as shown in FIG.

  The needle-shaped body produced using the plate obtained by the present invention can be used as a fine needle used for medical treatment, biological phenomenon, drug discovery, for example.

It is a schematic sectional drawing for demonstrating the manufacturing process of a plate mold over time. It is a figure which shows the pattern arrangement | positioning of the resist for deep digging formed on the silicon wafer. It is a schematic sectional drawing for demonstrating crystal anisotropic etching over time. It is a perspective view for demonstrating the acicular body obtained by transcribe | transferring using a plate type | mold.

Explanation of symbols

10 …… Silicon substrate (silicon wafer), 10a …… Silicon wafer surface, 10b …… Side side inside hole mold, 11 …… Resist mask, 12 …… (311) surface, 13 …… (111) surface, 14 …… Needle, θ …… Tip angle.

Claims (6)

A method of manufacturing a plate for forming a needle-like body, which can be integrally molded into an array,
(1) On the substrate, a mask is formed so as to have openings corresponding to a plurality of needles corresponding to a plurality of needle-like bodies, and a vertical direction corresponding to the main body of the needle-like bodies is formed using a dry etching method. Applying a first process for forming a deeply digged rectangular parallelepiped hole mold;
(2) peeling the mask and performing a second process of forming an inclined shape at a portion corresponding to the tip and root of the acicular body by crystal anisotropic etching;
The manufacturing method characterized by comprising.   The manufacturing method according to claim 1, wherein a material of the plate mold is silicon.   The manufacturing method according to claim 2, wherein a side surface of the rectangular parallelepiped hole shape deeply dug is a silicon (110) surface.   The manufacturing method according to claim 2 or 3, wherein an inclined shape corresponding to a tip portion of the needle-like body has a hole shape constituted by a (111) surface of silicon.   The manufacturing method according to any one of claims 2 to 4, wherein an inclined shape corresponding to a root portion of the needle-like body has a hole shape constituted by a (311) plane of silicon. A needle-shaped body using a biocompatible resin is formed using the plate mold manufactured by the manufacturing method according to claim 1.

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