JP2002079499A - Method of manufacturing needle-like article, and manufactured needle - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for manufacturing a need-like article with a through hole for supplying a chemical via a small number of steps, and a manu factured needle. SOLUTION: The method of manufacturing for a needlelike article forms a needlelike article by forming a plurality of grooves in one surface of a single- crystal substrate of metal, a metal compound or a semiconductor with both surfaces provided with a protective film against wet etching, to form a polygonal prism on the one surface of the substrate, and then immersing the single- crystal substrate in an etchant to etch the single-crystal material in an unnecessary portion. The needle is manufactured by this method.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing a needle-shaped object and a produced needle. More specifically, the present invention relates to a method for manufacturing a needle-shaped object having a through-hole for supplying a liquid near the base of the needle-shaped object, and a manufactured needle.

[0002]

2. Description of the Related Art In recent years, techniques for administering drugs into the body via human skin have been actively studied.
Japanese Patent Application Laid-Open No. -150147 discloses a technique in which a skin is wounded using a circular thin skin needle plate, and a medicinal solution is administered from the wound. However, according to the invention,
Since the wound formed on the skin is large and the invasion is large, it is desirable to use a device using a needle having a normal shape instead of a thin needle.

[0003] Japanese Patent Publication No. 9-504974 discloses an intradermal drug supply device using such a needle. However, since the device uses one needle, there is a problem that the dose of the drug solution per unit time is small.

Accordingly, as a method of forming a large number of minute needles, for example, “Microfabricated”
Microneedles: A Novel Ap
proch to Transdermal Dru
g Delivery ", J. Pharm. Pharmaceutical
al Sciences, vol. 87, no. 8,
1998. And "Micromachined Need
les for the Transdermal D
elyvery of Drugs ", Proceed
ins of MEMS 98, 1998. A method using a so-called drive process, such as a method using a special reactive ion etching apparatus or a method using an ECR plasma etching apparatus, is known. According to these methods, it is possible to process a so-called long and thin silicon needle utilizing high aspect ratio processing, but a special semiconductor processing device for exclusive use is required. Furthermore, in order to produce a needle shape having a through hole through which a chemical solution passes (not disclosed in the above-mentioned literature), the needle shape produced by the above-described technique is subjected to metal deposition, plating, or the like. Is also known, but the process becomes complicated and the number of processes increases.

[0005]

SUMMARY OF THE INVENTION Accordingly, it is an object of the present invention to provide a novel method for producing a needle-shaped article and a produced needle.

Another object of the present invention is to provide a method of manufacturing a needle-shaped object having a through-hole for supplying a chemical solution near the base of the needle-shaped object easily with a small number of steps, and to provide a manufactured needle. is there.

[0007]

The above objects are achieved by the following (1) to (6).

(1) A polygonal column is formed by forming a plurality of grooves on one side of a single crystal substrate of a metal, a metal compound or a semiconductor having a protective film for wet etching on both sides, and etching the single crystal substrate. A method for producing a needle-shaped object, characterized in that a needle-shaped object is formed by immersing the single-crystal material in an unnecessary portion by immersing it in a chemical solution.

(2) A first patterning for forming a needle shape is performed on one surface of a single crystal substrate of a metal, a metal compound or a semiconductor having a protection film against wet etching on both surfaces, and the single crystal is formed on another surface. The substrate is subjected to a second patterning for forming a through hole, and a groove is formed on the surface of the single crystal substrate on which the first patterning has been performed to form a polygonal prism, and the single crystal substrate is etched. A method for producing a needle-shaped object, wherein a needle-shaped object and a through-hole are formed simultaneously by immersing the single-crystal material in an unnecessary portion by immersing in a liquid agent.

(3) The height of the needle-shaped portion of the needle-shaped product is 10 to 500 μm, and the tip angle between the perpendicular from the vertex of the needle-shaped portion and the side is 2 to 60 °; The method according to (1) or (2), wherein the number of the needle-shaped portions formed on one single crystal substrate is one or more.

(4) The height and number of the needle-shaped portions are determined by the plane orientation, the size and the thickness of the single crystal substrate, the depth and interval of the plurality of grooves formed in the single crystal substrate, and the etching time. The method according to any one of the above (1) to (3), which can be set variously by changing.

(5) The method according to any one of (1) to (4), wherein the single crystal substrate is a silicon single crystal.

(6) A needle prepared by the method according to any one of the above (1) to (5), which is made of a single crystal material and has a polygonal pyramid shape at least from the needle tip to a predetermined length. needle.

[0014]

Next, an embodiment of the present invention will be described in detail with reference to the drawings.

As the substrate, a metal or metal compound such as silicon (Si), silicon carbide (SiC), or germanium (Ge), or a semiconductor single crystal wafer is used. Will be described as an example.

First, a silicon wafer having both sides (100) polished on one or both sides is prepared, and as a cleaning before forming a protective film, for example, a mixed solution of sulfuric acid and hydrogen peroxide at a ratio of 2: 1 is used. For 10 to 20 minutes, and then ultrapure water cleaning. Further, the substrate is washed with dilute hydrofluoric acid (a mixture of hydrofluoric acid and ultrapure water at a ratio of 1:50) for 15 to 30 seconds, washed with ultrapure water, and further dried.

Next, 800 to 11 using a heat diffusion furnace.
Heat treatment was performed at 00 ° C. for 40 to 60 minutes, and FIG.
As shown in FIG. 1, oxide films 2a and 2b having a thickness of about 0.1 to 0.5 .mu.m are formed on both surfaces of the substrate 1 to serve as protective films during etching (see FIG. 1A).

Further, a resist, for example, a negative resist is applied to one surface of the substrate 1 on which the silicon oxide films 2a and 2b are formed by using a resist coating device (not shown), and the resist is coated to a thickness of 0.5 to 1.5 μm. Is formed (see FIG. 1B), prebaked at a temperature of 70 to 80 ° C., and then exposed using a dicing groove forming mask 4 (see FIG. 1C). The shape of the mask may be any shape as long as the pattern formed on the silicon oxide film by use of the mask 4 functions as a mark for dicing positions (groove forming positions) in a dicing step described later. It may be something.

Next, the silicon oxide film at the groove forming position 5a is removed by developing using a developing device (see FIG. 1D).

Next, a resist layer 3b having a similar thickness is formed on a surface on the opposite side of the substrate 1 by using a resist coating device (not shown), prebaked under similar conditions, and then a dicing groove is formed. Exposure is performed using a forming mask (not shown), and development is performed using a developing device (not shown) to remove the silicon oxide film at the groove formation position 5b (see FIG. 1E). However, at the time of exposure, the pattern of the dicing groove formation formed in the silicon oxide films 2a and 2b is set on the back side (so that the formation position of the through hole formed in the later-described etching does not deviate from the formation position of the needle-shaped object. Since it is necessary to match the pattern of the substrate 1 (the surface on which the needle-shaped object is formed), exposure is performed using a double-sided mask liner that can recognize both the front side and the back side of the substrate 1.

Thereafter, post baking is performed at a temperature of 100 to 120.degree. The order of patterning may be from either mask.

Next, as shown in FIG. 2, the silicon oxide film in the portion exposed by patterning is removed with buffered hydrofluoric acid (a mixed solution of hydrofluoric acid and ammonium fluoride).
Then, the resists 3a and 3b are peeled off (see FIG. 2F). To remove the resist, the resist is immersed in a remover heated to 100 to 120 ° C. (for example, 502A, manufactured by Tokyo Ohka Kogyo Co., Ltd.). It is taken out and placed in a strip rinse (trade name) containing a diethylene glycol monobutyl ether or monoethanolamine solution, and the resist stripping solution is replaced while applying ultrasonic waves, and then further replaced with isopropanol. Then, it is washed with ultrapure water and further dried.

The substrate 1 after the patterning is diced (see FIG. 2G). Silicon wafer (substrate) 1
Is set on the dicing saw so that the dicing pattern comes to the front. The wafer (substrate) is aligned (positioned) with a predetermined dicing apparatus such that the orientation flat (the (110) plane in this case) of the dicing blade and the wafer (substrate) is parallel. The dicing blade is set at a height that does not cut the wafer (substrate), and the dicing apparatus is programmed to perform dicing so that the dicing blade performs predetermined dicing on the dicing pattern. Since dicing is performed in a grid pattern, when the first dicing is completed, the wafer is rotated 90 degrees and dicing is performed in the same manner. Thus, a prismatic wafer (substrate) structure is manufactured as shown in FIG.

Next, the wafer (substrate) 1 after completion of the dicing is heated to 90 to 130 ° C., preferably 100 to 110 ° C.
The substrate is etched by immersing it in an etching solution heated to ° C. for 20 to 80 minutes, preferably 40 to 60 minutes. Thereafter, the substrate is taken out, washed with water, and further dried.

When the substrate is a silicon wafer, for example, a 25% by weight aqueous solution of tetramethylammonium hydroxide and a 20% aqueous solution of potassium hydroxide are used.
There is an aqueous solution of about weight%, a mixed solution of ethylenediamine, pyrocatechol and water, and the like. Also, when the substrate is germanium, the same etchant as silicon can be used.

In such an etching step, the portion of the substrate 1 above and below the broken line in FIG. 2G is etched, and there is a through hole 8 in the flat plate portion 10 formed from the bottom of the substrate as shown in FIG. 2H. A sword-yama type microneedle 9 is formed. The reason why the needle-like shape remains and is etched in the substrate 1 and the portion of the through hole 8 is etched in the substrate 1 is considered to be due to anisotropic etching of the single crystal wafer. For example, in the case of a silicon wafer, (10
A crystal plane (nn1) having a higher etch rate than the 0) plane appears, and the shape collapse of the island proceeds rapidly. n depends on the conditions of the etchant and varies in the range of n = 2-4. As the etching progresses, the vicinity of the center of the prism-shaped structure (see FIG. 4A) narrows (see FIG. 4B), and eventually the erosion on the etching protective film side separates the silicon from the substrate 1,
The structure remaining on the substrate 1 eventually becomes a needle shape (see FIG. 4C).

The substrate thus obtained is cut, for example, in the direction of the arrow to obtain the substrate shown in FIGS. 2I, 5 and 6.
The needle-shaped object shown in (micrograph) is obtained. That is,
A quadrangular pyramid-shaped needle-shaped object 9 is formed on the substrate 1 (flat portion 1a), and penetrates the substrate 1 (flat portion 1a) near the base of the slope of the needle-shaped object 9. A through hole 8 is formed.

Next, as another embodiment, a method for forming a plurality of needle-shaped objects on one substrate as shown in FIG. 7 will be described.

First, FIGS. 1A to 1E and FIGS. 2F to 2
In the same manner as in the step I, the silicon wafer 11 having a plane orientation of (100) is polished on both sides and treated similarly, and then the same oxide films 12a and 12b are formed on both sides, a resist is applied, and then masking is performed. After exposure, development is performed, and the silicon oxide film 12 at the groove formation positions 16a and 16b is formed.
a and 12b are removed.

Next, after the portions of the silicon oxide films 12a and 12b exposed by patterning are removed, the resist is removed (see FIG. 7A). The substrate (wafer) 11 after the patterning is diced (see FIG. 7B). Similar to the steps of FIGS. 1A to 1E and FIGS. 2F to 2I, alignment with a dicing apparatus is performed, and dicing is performed to form a recessed portion 17 (see FIG. 7B).

Next, the wafer (substrate) 11 after completion of dicing is etched in the same manner as described above, and then the substrate 11 is taken out, washed with water, and further dried.

In such an etching step, the upper and lower portions of the substrate 11 are etched by broken lines in FIG. 7B, and the through holes 18 are formed in the flat plate portion 11a formed from the bottom of the substrate 11 as shown in FIG. 7C. A plurality of micro needles 19 of a certain sword mountain type are formed. Thus, the substrate 11
In, it is considered that the reason why the needle-like shape remains and is etched and the portion of the through hole 18 is etched is due to the anisotropic etching of the single crystal wafer.

By cutting the substrate thus obtained, for example, in the direction of the arrow, the needle-shaped object shown in FIG. 7D is obtained. That is, a quadrangular pyramid-shaped needle-shaped object 19 is formed on the substrate 11, and a through hole 18 penetrating through the substrate 11 is provided near the base of the slope of the needle-shaped object 19.
Is formed.

In the above embodiment, a description has been given of a production example in which the formation of the needle-shaped object and the formation of the through-hole are simultaneously performed in the same etching step. However, the present invention is not limited to this, and is shown in FIG. As described above, the needle-shaped object forming step and the through-hole forming step may be performed separately. If the step of forming a through hole is omitted, a solid needle is manufactured.

That is, similarly to the above embodiment, an oxide film 22 is formed on both surfaces of a silicon wafer (substrate) 21 as a protective film.
a and 22b, and then using dicing and patterning (see FIG. 8A), a silicon wafer (substrate) 2
Etching 1 is performed to form a recess 30 having a tip angle of about 70 ° (see FIG. 8B). Thereafter, dicing is performed (see FIG. 8C), and the silicon wafer is further etched to form needle-like projections 29 having through holes 28 (see FIG. 8D). Next, the needle-shaped object shown in FIG. 8E is obtained by cutting a predetermined portion in the direction of the arrow.

The height H from the surface of the substrate 1 of the needle-shaped object obtained by the above method is 10 to 500 μm, preferably 150 to 300 μm, and the width D6.5 to 325 of the bottom side.
μm, preferably 100 to 195 μm (see FIG. 5). The tip angle θ between the perpendicular A from the vertex of the needle portion toward the flat plate portion and the inclination of the side B is 2 to 60.
°. The thickness of the flat portion is 100 μm or more.

As described above, when the grooves are formed in a grid pattern as shown in FIG. 3 to form a quadrangular prism, a pyramid-like needle-shaped object having a quadrilateral bottom surface is formed. In addition, even when it is formed from a square pole, as shown in FIG.
On the opposite side, an octagonal pyramid shape 31 may be exhibited, and a through hole 38 may be provided.

The needle-shaped product thus obtained is described, for example, in US Pat. No. 3,964,482, Japanese Patent Application Laid-Open No. 9-504.
No. 974, Japanese Patent Application Laid-Open No. 10-510175, etc., the needle-shaped object is attached to a drug supply device, and the needle-shaped object is pressed into the skin of the patient and inserted into the skin, thereby allowing the body to pass through the skin of the patient and into the body. The necessary drugs can be administered painlessly.

[0039]

Next, the present invention will be described in more detail with reference to examples.

Example 1 Formation of SiO ₂ film for etching mask A silicon wafer [Si (100) n-type] having a thickness of 450 μm and single-side polishing and having a diameter of 3 inches was prepared, and a 2: 1 ratio of sulfuric acid to hydrogen peroxide was used. Was washed at a temperature of 120 ° C. for 20 minutes, and then washed with ultrapure water. Next, the substrate was washed with a mixed aqueous solution of ammonia: hydrogen peroxide: water at a ratio of 1: 1: 5 at a temperature of 80 ° C. for 15 minutes, and then washed with ultrapure water. Furthermore, hydrochloric acid: hydrogen peroxide water: water is 1:
After washing with a mixed aqueous solution at a ratio of 1: 5 at a temperature of 80 ° C. for 15 minutes, it was washed with ultrapure water. Further, the substrate was washed with a mixed aqueous solution of hydrofluoric acid and water at a ratio of 1:50 for 30 seconds, washed with ultrapure water, and spun-dried.

The silicon wafer thus processed is inserted into a furnace at an insertion temperature of 400 ° C., and is processed at a temperature of 1100 ° C. for 60 minutes to form a film having a thickness of 0.5 on both surfaces of the silicon wafer.
A μm silicon oxide film was formed (see FIG. 1A).

SiO2 patterning photolithography (formation of back window) A negative resist (OMR8360CP manufactured by Tokyo Ohka Kogyo Co., Ltd.) was applied to a polished surface of the wafer 1 to a thickness of 1.5 μm. 1 (Canon CDS-63
0) pre-baked at 80 ° C and further 5 ° C at 120 ° C.
After that, post-baking was performed for a surface protection coat (Fig. 1).
B).

Next, a negative resist (OMR8360CP manufactured by Tokyo Ohka Co., Ltd.) was applied to a thickness of 1.5 μm, and the program No. 1 (Canon CDS-63)
0) and pre-bake at 80 ° C.
Masking using MD-2) and exposure for 7 seconds with Micasa Aligner. 5 (Canon
Post-baking was performed at 140 ° C. with CDS-630) to perform photolithography (see FIG. 1C).

Further, after etching with a BHF etching solution of hydrofluoric acid and ammonium fluoride at a ratio of 1: 4 for 10 minutes, the substrate was washed with ultrapure water, spin-dried, and subjected to SiO ₂ etching.

Next, the stripper (502A, manufactured by Tokyo Ohka Kogyo Co., Ltd.) was rocked at 120 ° C. every 3 minutes for 6 minutes, and then strip rinse (strip rinse, manufactured by Tokyo Oka Kogyo Co., Ltd.) was performed. Replacement ultrasonic cleaning 1
For 1 minute, followed by isopropanol replacement for 1 minute, further dump rinse, and spin dry to remove the resist.

SiO2 patterning photolithography (formation of surface alignment mark) A negative resist (OMR8360CP manufactured by Tokyo Ohka Co., Ltd.) was applied to a non-polished surface of the wafer 1 to a thickness of 1.5 μm. 1 (Canon CDS-63)
0) prebaking at 80 ° C,
After that, post-baking was performed for a surface protection coat.

Next, a negative resist (OMR8360CP manufactured by Tokyo Ohka Kogyo Co., Ltd.) was applied to a thickness of 1.5 μm, and the program No. 1 (Canon CDS-63)
0) at 80 ° C. and a mask (AW
Masking using SM-2) and exposure of 100 mj using a mask aligner manufactured by Union Optical Co., Ltd.
o. 5 (Canon CDS-630) and post-baking at 140 ° C. to perform photolithography.

Further, after etching with a BHF etching solution of hydrofluoric acid and ammonium fluoride at a ratio of 1: 4 for 10 minutes, the substrate was washed with ultrapure water, spin-dried, and subjected to SiO ₂ etching.

Next, the stripper (502A, manufactured by Tokyo Ohka Kogyo Co., Ltd.) was rocked at 120 ° C. every 3 minutes for 6 minutes, and then strip rinse (strip rinse, manufactured by Tokyo Oka Kogyo Co., Ltd.) was performed. Substitution ultrasonic cleaning was performed for 1 minute, then isopropanol substitution was performed for 1 minute, dump rinse was performed, and spin drying was performed to remove the resist. (See FIG. 1F) Si anisotropic etching (back window-surface alignment mark type) After immersing in hydrazine at an oil bath set temperature of 135 ° C. for 60 minutes with the back window surface of the wafer facing up, the wafer is washed with ultrapure water. Was replaced with isopropanol for 30 seconds and then dried in an oven at 50 ° C. (see FIG. 2G).

Dicing (Formation of Micro Needles) The wafer is diced with a dicing saw (DISCO DAD-3).
21, blade height 0.19 mm). Si anisotropic etching (microneedle formation) The wafer is immersed in a 25% by weight aqueous solution of tetramethylammonium hydroxide at an oil bath set temperature of 110 ° C. for 45 minutes with the polished surface facing up, and then washed with ultrapure water. Replaced with isopropanol for 30 seconds and then dried in an oven at 50 ° C. (see FIG. 2H).

Observation of Shape The obtained microneedles were observed with a scanning electron microscope, and the height was measured with a THS (non-contact thickness measuring device, manufactured by Union Optical Co., Ltd.). Is about 120 μm, the width D of the base of the needle is about 80 μm, the tip angle θ (see FIG. 5) between the vertical line from the vertex of the needle-shaped part and the side surface is about 25 °, and near the base of the slope. Had a through hole of about 40 μm on each side. The thickness of the flat plate below the needle is about 150μm
Met. This was cut in the direction of the arrow in FIG. 2H to obtain a microneedle.

[0052]

As described above, according to the present invention, a needle-shaped object can be easily produced from a single crystal substrate of a metal or a metal compound in a small number of steps. One having a through hole for supplying a chemical solution or the like near the root can be manufactured. Therefore, such a needle-shaped article has an advantage that it can be used as a painless percutaneous injection needle.

[Brief description of the drawings]

FIG. 1 is a cross-sectional view showing a part of a process for producing a needle-shaped object according to the present invention.

FIG. 2 is a cross-sectional view showing the remaining steps of the manufacturing process shown in FIG.

FIG. 3 is a perspective view showing a prism portion formed during the manufacturing process according to the present invention.

FIG. 4 is a schematic perspective view showing a change in a shape state of a needle-like portion in a manufacturing process according to the present invention.

FIG. 5 is a perspective view showing a needle-shaped object manufactured according to the present invention.

FIG. 6 is a scanning micrograph of a needle-shaped article produced according to the present invention.

FIG. 7 is a sectional view showing the steps of another embodiment of the needle-shaped article according to the present invention.

FIG. 8 is a cross-sectional view showing the steps of still another embodiment of the needle-shaped article according to the present invention.

FIG. 9 is a perspective view showing another embodiment of the needle-shaped object according to the present invention.

[Explanation of symbols]

1, 11, 21 ... substrate, 2a, 2b, 12a, 12b, 22a, 22b ... oxide film, 3a, 3b, 13a, 13b, 23a, 23b ... resist layer, 4 ... mask, 5a, 5b ... groove formation position, 6a, 6b: oxide film removed portion, 7: concave portion, 8, 18, 28: through hole, 9, 19, 29: microneedles.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) H01L 21/306 H01L 21/306 BF Term (Reference) 4C060 MM01 MM22 4K057 WA19 WB06 WC06 WE07 WG01 WG02 WM03 WN10 5F043 AA02 AA31 BB02 BB22 DD02 FF01 GG10

Claims (6)

[Claims] 1. A polygonal column formed by forming a plurality of grooves on one side of a metal or metal compound or semiconductor single crystal substrate provided with a protective film on both surfaces for wet etching, and forming the single crystal substrate with an etchant. By immersing in the liquid and etching the unnecessary part of the single crystal material,
A method for producing a needle-shaped object, comprising forming a needle-shaped object. 2. A first patterning for forming a needle shape on one surface of a metal or metal compound or semiconductor single crystal substrate having both surfaces provided with a protective film against wet etching, and another single surface of the single crystal substrate Is subjected to a second patterning for forming a through hole, and a groove is formed on the surface of the single crystal substrate on which the first patterning has been performed, thereby forming a polygonal prism, and etching the single crystal substrate with an etching agent. A method for producing a needle-shaped object, wherein a needle-shaped object and a through-hole are simultaneously formed by immersing the single crystal material in an unnecessary portion by dipping in a liquid. 3. The needle-shaped part of the needle-shaped object has a height of 10 to 10.
500 μm, a tip angle between a perpendicular from a vertex of the needle-shaped portion and a side is 2 to 60 °, and one or more needle-shaped portions formed on one single crystal substrate are provided. The method according to claim 1, wherein the number is one. 4. The height and number of said needle-shaped portions change the plane orientation, size and thickness of said single crystal substrate, depth and interval of said plurality of grooves formed in said single crystal substrate, and etching time. The method according to any one of claims 1 to 3, wherein the method can be set in various ways. 5. The method according to claim 1, wherein said single crystal substrate is a silicon single crystal. 6. A needle prepared by the method according to claim 1 and made of a single crystal material,
A needle having a polygonal pyramid shape at least from the needle tip to a predetermined length.