CN114590773A - Manufacturing process of silicon-based nano microneedle array for transdermal drug delivery - Google Patents

Manufacturing process of silicon-based nano microneedle array for transdermal drug delivery Download PDF

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CN114590773A
CN114590773A CN202210257117.2A CN202210257117A CN114590773A CN 114590773 A CN114590773 A CN 114590773A CN 202210257117 A CN202210257117 A CN 202210257117A CN 114590773 A CN114590773 A CN 114590773A
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etching
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胡玉龙
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B81—MICROSTRUCTURAL TECHNOLOGY
    • B81C—PROCESSES OR APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OR TREATMENT OF MICROSTRUCTURAL DEVICES OR SYSTEMS
    • B81C1/00—Manufacture or treatment of devices or systems in or on a substrate
    • B81C1/00015—Manufacture or treatment of devices or systems in or on a substrate for manufacturing microsystems
    • B81C1/00023—Manufacture or treatment of devices or systems in or on a substrate for manufacturing microsystems without movable or flexible elements
    • B81C1/00031—Regular or irregular arrays of nanoscale structures, e.g. etch mask layer
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B81—MICROSTRUCTURAL TECHNOLOGY
    • B81C—PROCESSES OR APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OR TREATMENT OF MICROSTRUCTURAL DEVICES OR SYSTEMS
    • B81C1/00—Manufacture or treatment of devices or systems in or on a substrate
    • B81C1/00015—Manufacture or treatment of devices or systems in or on a substrate for manufacturing microsystems
    • B81C1/00023—Manufacture or treatment of devices or systems in or on a substrate for manufacturing microsystems without movable or flexible elements
    • B81C1/00111—Tips, pillars, i.e. raised structures
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B81—MICROSTRUCTURAL TECHNOLOGY
    • B81C—PROCESSES OR APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OR TREATMENT OF MICROSTRUCTURAL DEVICES OR SYSTEMS
    • B81C1/00—Manufacture or treatment of devices or systems in or on a substrate
    • B81C1/00388—Etch mask forming
    • B81C1/00404—Mask characterised by its size, orientation or shape
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B81—MICROSTRUCTURAL TECHNOLOGY
    • B81C—PROCESSES OR APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OR TREATMENT OF MICROSTRUCTURAL DEVICES OR SYSTEMS
    • B81C1/00—Manufacture or treatment of devices or systems in or on a substrate
    • B81C1/00436—Shaping materials, i.e. techniques for structuring the substrate or the layers on the substrate
    • B81C1/00523—Etching material
    • B81C1/00531—Dry etching
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B81—MICROSTRUCTURAL TECHNOLOGY
    • B81C—PROCESSES OR APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OR TREATMENT OF MICROSTRUCTURAL DEVICES OR SYSTEMS
    • B81C1/00—Manufacture or treatment of devices or systems in or on a substrate
    • B81C1/00436—Shaping materials, i.e. techniques for structuring the substrate or the layers on the substrate
    • B81C1/00523—Etching material
    • B81C1/00539—Wet etching
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/0023—Drug applicators using microneedles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/0046—Solid microneedles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/0053—Methods for producing microneedles

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Abstract

The invention discloses a manufacturing process of a silicon-based nano microneedle array for transdermal drug delivery, which comprises the following steps: s1: depositing a silicon dioxide oxide layer on a silicon substrate; s2: photoetching and developing, namely coating a layer of photoresist on the surface of the silicon dioxide oxide layer, covering the photoresist by using a mask plate with regularly distributed patterns for exposure, and then carrying out developing operation to form the patterns on the mask plate on the photoresist; s3: wet etching, etching the silicon dioxide oxide layer which is not masked by the photoresist, and transferring the pattern on the photoresist to the silicon dioxide oxide layer; s4: dry etching, namely etching the silicon substrate in a mode of etching while protecting to obtain a nano microneedle array structure with a narrow upper part and a wide lower part; s5: and removing the silicon dioxide oxidation layer by a wet method, and removing the silicon dioxide oxidation layer and the photoresist on the top of the silicon substrate to obtain the silicon-based nano microneedle array for transdermal drug delivery. The process can realize the large-area and high-efficiency manufacture of the micro-needle.

Description

Manufacturing process of silicon-based nano microneedle array for transdermal drug delivery
The technical field is as follows:
the invention relates to the technical field of micro-nano structure manufacturing, in particular to a manufacturing process of a silicon-based nano microneedle array for transdermal drug delivery.
Background art:
although modern biotechnology has produced extremely mature and effective drugs, the effective delivery of many drugs is limited by current delivery technologies (oral and injectable). Among the major problems of oral administration are the degradation of the drug in the gastrointestinal tract and the expulsion of the drug through the liver; another common intravenous injection is not easy to use in non-medical places, is not good for maintaining and controlling the release of the drug, is inconvenient for patients and has certain pain. Thus, transdermal drug delivery is a new and effective delivery method, but this method is limited by the extremely poor permeability of the skin. The micro-needle array can enhance the transmission of drug molecules through the skin to realize high-efficiency and painless drug delivery, and after the micro-needle array penetrates into the skin, a conduit for transmitting the drug through the stratum corneum is created, once the drug passes through the stratum corneum, the drug can rapidly diffuse through deep tissues and be absorbed by the underlying capillary vessels to form a drug delivery system.
The micro-needle array for transmitting the calcein by the engineering institute of georgia is manufactured by using a reactive ion etching technology, has the length of 150 mu m and the diameter of 50-80 mu m, and is formed into a 20 multiplied by 20 micro-needle array. When microneedles were inserted into the skin in the test, they showed excellent mechanical properties and enhanced skin permeability to calcein, a mode agent, which is increased by 4 orders of magnitude. The hollow microneedle array for conveying insulin, developed by Burkeley Sensor and Actuator center of university of California, USA, suspends the drug in an anhydrous viscous solution, prevents the drug from flowing out of the device, and ensures complete transmission through the microneedle array, wherein the diameter of a microneedle pipeline is 40 μm, the height of the microneedle is 200 μm, and the curvature radius of a needle point is 100 nm; experiments have shown that microneedle arrays can be successfully inserted 100 μm under the skin to achieve highly efficient delivery of insulin. Transdermal microneedle administration has a wide range of drug applications, and also includes macromolecular compounds. The microneedle array which is manufactured by Swedish Stockholm royal institute of Engineers and is used for drug delivery with side openings adopts microneedles with openings on the shaft instead of microneedles with openings at the upper ends, and tests show that the microneedle array has small resistivity for transferring fluid, high mechanical strength, no damage to the microneedle array after being pierced and taken out, and the length of the microneedle array is 210 mu m; in addition, the U.S. Louisiana State university and Texas university developed arrays of polymeric PMMA and metallic Ni microneedles for drug delivery having a height of 200 μm and inner to outer diameter dimensions ranging from 20-40 μm and 40-80 μm using the LIGA process. The new manufacturing process has led to the rapid development of microneedle arrays, the design and fabrication of which is an extremely important step in the development of new transdermal drug delivery systems. Experiments have shown that current microneedles have sufficient strength to support the pressure throughout the delivery process.
However, due to the imperfect existing production process, such as uneven distribution of etching gas during etching, the large-area consistency of the etched microneedle structure is poor, which is not conducive to industrial popularization.
The information disclosed in this background section is only for enhancement of understanding of the general background of the invention and should not be taken as an acknowledgement or any form of suggestion that this information forms the prior art already known to a person skilled in the art.
The invention content is as follows:
the present invention aims to provide a manufacturing process for transdermal administration of silicon-based nano microneedle arrays, which overcomes the above-mentioned drawbacks of the prior art.
In order to achieve the above object, the present invention provides a manufacturing process for transdermal administration of a silicon-based nano microneedle array, comprising the steps of:
s1: depositing a silicon dioxide oxide layer on a silicon substrate;
s2: photoetching and developing, namely coating a layer of photoresist on the surface of the silicon dioxide oxide layer, covering the photoresist by using a mask plate with regularly distributed patterns for exposure, and then carrying out developing operation to form the patterns on the mask plate on the photoresist;
s3: wet etching, etching the silicon dioxide oxide layer which is not masked by the photoresist, and transferring the pattern on the photoresist to the silicon dioxide oxide layer;
s4: dry etching, namely etching the silicon substrate in a mode of etching while protecting to obtain a nano microneedle array structure with a narrow upper part and a wide lower part;
s5: and removing the silicon dioxide oxidation layer by a wet method, and removing the silicon dioxide oxidation layer and the photoresist on the top of the silicon substrate to obtain the silicon-based nano microneedle array for transdermal drug delivery.
Preferably, the silicon substrate in the step S1 is a silicon substrate with a polished single surface, the thickness is 400-600 μm, the silicon substrate is cleaned by acetone, ethanol and deionized water during deposition, then dried by nitrogen, and then a silicon dioxide oxide layer is deposited by a chemical vapor deposition (PECVD) method.
Preferably, the photoresist in S2 is coated by spin coating to a thickness of 1-1.5 μm, and then pre-baked on a baking table at 75-95 deg.C for 5-10 min.
Preferably, the exposure time in S2 is 6-10S, and the silicon substrate is placed in a 5% by mass NaOH solution for development.
Preferably, hydrofluoric acid is adopted in the etching in the step S3 in a volume ratio: ammonium fluoride: deionized water =3:6:10 mixed solution for etching.
Preferably, the etching and protecting in S4 specifically includes: etching gas is SF6, the flow is 130sccm, the etching time is 9 +/-1 s, and the radio frequency power of the induction coil is 600W; the protective gas is C4F8, the gas flow is 85sccm, the introduction time of the protective gas is 7 +/-1 s, and the radio frequency power of the induction coil is 600W; and (4) circularly etching and protecting every 16-17 seconds.
Preferably, the microneedle tip size of the nano microneedle array structure with the narrow top and the wide bottom in the S4 is less than 5 μm, the diameter of the microneedle bottom is 50-150 μm, and the microneedle height is 50-200 μm.
Preferably, the shape of the microneedle bottom in S4 is a circle, a square, an octagon or other polygons.
Preferably, in S5, the product ratio is hydrofluoric acid: ammonium fluoride: the mixed solution of deionized water =3:6:10 removes the silicon dioxide oxide layer and the photoresist.
Preferably, the photoresist is EPG533 photoresist.
Compared with the prior art, the invention has the following beneficial effects:
according to the invention, by designing the pattern structure on the mask, the error of the radial etching rate of the silicon substrate can be compensated, so that the final structure of the micro-needle on the whole silicon substrate can be kept consistent, and the large-area and high-efficiency manufacture of the micro-needle is realized.
Description of the drawings:
fig. 1 is a schematic flow chart of a manufacturing process for transdermal administration of a silicon-based nano microneedle array according to the present invention;
the reference signs are: 1-silicon substrate, 2-silicon dioxide oxide layer and 3-photoresist.
The specific implementation mode is as follows:
the following detailed description of specific embodiments of the invention is provided, but it should be understood that the scope of the invention is not limited to the specific embodiments.
Example 1:
as shown in fig. 1, a manufacturing process for transdermal administration of a silicon-based nano microneedle array includes the following steps:
s1: depositing a silicon dioxide oxide layer on a silicon substrate;
specifically, a silicon substrate with a polished single surface and a thickness of 400 μm is selected, cleaned by acetone, ethanol and deionized water, blown dry by nitrogen, and then a silicon dioxide oxide layer with a thickness of 400nm is deposited on the upper surface of the silicon substrate by a chemical vapor deposition (PECVD) method;
s2: photoetching and developing, namely coating a layer of photoresist on the surface of the silicon dioxide oxide layer, covering the photoresist by using a mask plate with regularly distributed patterns for exposure, and then carrying out developing operation to form the patterns on the mask plate on the photoresist;
specifically, a layer of EPG533 photoresist with the thickness of 1 μm is uniformly coated on a silicon dioxide oxide layer by adopting a spin-coating method, and is pre-dried for 5 minutes on a drying table at the temperature of 95 ℃; covering the EPG533 photoresist by using a mask plate with a mask pattern which is regularly distributed as a circular pattern, and then exposing for 8 s; finally, the whole silicon substrate is placed in 5 per mill NaOH solution by mass percent for development, and a pattern on a mask is formed on the EPG533 photoresist;
s3: wet etching, etching the silicon dioxide oxide layer which is not masked by the photoresist, and transferring the pattern on the photoresist to the silicon dioxide oxide layer;
specifically, the volume ratio of hydrofluoric acid: ammonium fluoride: the deionized water =3:6:10 solution corrodes the silicon dioxide oxide layer which is not masked by the EPG533 photoresist, and the pattern on the EPG533 photoresist is transferred to the silicon dioxide oxide layer;
s4: dry etching, namely etching the silicon substrate in a mode of etching while protecting to obtain a nano microneedle array structure with a narrow upper part and a wide lower part;
specifically, tetrafluoromethane dry etching silicon substrate is adoptedOne side of the photo-etched substrate is adjusted by C4F8And SF6The gas concentration ratio of (1) to obtain a nano microneedle structure with narrow top and wide bottom, more specifically, the technology of etching while protecting is adopted, and etching gas is SF6The gas flow is 130sccm, the etching time is 9 +/-1 s, and the radio frequency power of the induction coil is 600W; the protective gas is C4F8The gas flow is 85sccm, the introduction time of the protective gas is 7 +/-1 s, the radio frequency power of the induction coil is 600W, and the etching and protection are performed once every 16-17 seconds in a circulating manner. The size of the needle point of the prepared micro-needle is less than 5 mu m, and the diameter of the bottom of the micro-needle is 50 mu m; the microneedles were 50 μm in height.
S5: and removing the silicon dioxide oxidation layer by a wet method, and removing the silicon dioxide oxidation layer and the photoresist on the top of the silicon substrate to obtain the silicon-based nano microneedle array for transdermal drug delivery.
Specifically, the volume ratio of hydrofluoric acid: ammonium fluoride: deionized water =3:6:10 solution corrodes the "cap" on top of the silicon substrate microneedle (i.e. the silicon dioxide oxide layer and the photoresist) to obtain the silicon substrate nano microneedle array for transdermal drug delivery.
Example 2:
as shown in fig. 1, a manufacturing process for transdermal administration of a silicon-based nano microneedle array includes the following steps:
s1: depositing a silicon dioxide oxide layer on a silicon substrate;
specifically, a silicon substrate with a single-side polishing thickness of 500 microns is selected, cleaned by acetone, ethanol and deionized water, blown dry by nitrogen, and then a silicon dioxide oxide layer with a thickness of 500nm is deposited on the upper surface of the silicon substrate by a chemical vapor deposition (PECVD) method;
s2: photoetching and developing, namely coating a layer of photoresist on the surface of the silicon dioxide oxide layer, covering the photoresist by using a mask plate with regularly distributed patterns for exposure, and then carrying out developing operation to form the patterns on the mask plate on the photoresist;
specifically, a layer of EPG533 photoresist with the thickness of 1.2 μm is uniformly coated on a silicon dioxide oxide layer by adopting a spin-coating method, and is pre-baked for 8 minutes on a baking table at the temperature of 85 ℃; covering the EPG533 photoresist by using a mask plate with a mask pattern which is regularly distributed as a circular pattern, and then exposing for 8 s; finally, the whole silicon substrate is placed in 5 per mill NaOH solution by mass percent for development, and a pattern on a mask is formed on the EPG533 photoresist;
s3: wet etching, etching the silicon dioxide oxide layer which is not masked by the photoresist, and transferring the pattern on the photoresist to the silicon dioxide oxide layer;
specifically, the volume ratio of hydrofluoric acid: ammonium fluoride: the deionized water =3:6:10 solution corrodes the silicon dioxide oxide layer which is not masked by the EPG533 photoresist, and the pattern on the EPG533 photoresist is transferred to the silicon dioxide oxide layer;
s4: dry etching, namely etching the silicon substrate in a mode of etching while protecting to obtain a nano microneedle array structure with a narrow upper part and a wide lower part;
specifically, a tetrafluoromethane dry etching method is adopted to etch the photoetched surface of the silicon substrate, and C is adjusted4F8And SF6The gas concentration ratio of (1) to obtain the nano microneedle structure with narrow top and wide bottom, more specifically, the technology of etching and protecting is adopted, and the etching gas is SF6The gas flow is 130sccm, the etching time is 9 +/-1 s, and the radio frequency power of the induction coil is 600W; the protective gas is C4F8The gas flow is 85sccm, the introduction time of the protective gas is 7 +/-1 s, the radio frequency power of the induction coil is 600W, and the etching and protection are performed once in a cycle every 16-17 seconds. The size of the needle point of the prepared microneedle is less than 5 mu m, and the diameter of the bottom of the microneedle is 100 mu m; the microneedles were 100 μm in height.
S5: and removing the silicon dioxide oxidation layer by a wet method, and removing the silicon dioxide oxidation layer and the photoresist on the top of the silicon substrate to obtain the silicon-based nano microneedle array for transdermal drug delivery.
Specifically, the volume ratio of hydrofluoric acid: ammonium fluoride: deionized water =3:6:10 solution corrodes the "cap" on top of the silicon substrate microneedle (i.e. the silicon dioxide oxide layer and the photoresist) to obtain the silicon substrate nano microneedle array for transdermal drug delivery.
Example 3:
as shown in fig. 1, a manufacturing process for transdermal delivery of a silicon-based nano microneedle array comprises the following steps:
s1: depositing a silicon dioxide oxide layer on a silicon substrate;
specifically, a silicon substrate with a single-side polishing thickness of 600 microns is selected, cleaned by acetone, ethanol and deionized water, blown dry by nitrogen, and then a silicon dioxide oxide layer with a thickness of 600nm is deposited on the upper surface of the silicon substrate by a chemical vapor deposition (PECVD) method;
s2: photoetching and developing, namely coating a layer of photoresist on the surface of the silicon dioxide oxide layer, covering the photoresist by using a mask plate with regularly distributed patterns for exposure, and then carrying out developing operation to form the patterns on the mask plate on the photoresist;
specifically, a layer of EPG533 photoresist with the thickness of 1.5 μm is uniformly coated on a silicon dioxide oxide layer by adopting a spin-coating method, and is pre-dried for 10 minutes on a 95 ℃ drying table; covering the EPG533 photoresist by using a mask plate with a mask pattern which is regularly distributed as a circular pattern, and then exposing for 10 s; finally, the whole silicon substrate is placed in 5 per mill NaOH solution by mass percent for development, and a pattern on a mask is formed on the EPG533 photoresist;
s3: wet etching, etching the silicon dioxide oxide layer which is not masked by the photoresist, and transferring the pattern on the photoresist to the silicon dioxide oxide layer;
specifically, the volume ratio of hydrofluoric acid: ammonium fluoride: the deionized water =3:6:10 solution corrodes the silicon dioxide oxide layer which is not masked by the EPG533 photoresist, and the pattern on the EPG533 photoresist is transferred to the silicon dioxide oxide layer;
s4: dry etching, namely etching the silicon substrate in a mode of etching while protecting to obtain a nano microneedle array structure with a narrow upper part and a wide lower part;
specifically, a tetrafluoromethane dry etching method is adopted to etch the photoetched surface of the silicon substrate, and C is adjusted4F8And SF6The gas concentration ratio of (1) to obtain a nano microneedle structure with narrow top and wide bottom, more specifically, the technology of etching while protecting is adopted, and etching gas is SF6The gas flow is 130sccm, the etching time is 9 +/-1 s, and the radio frequency power of the induction coil is 600W; the protective gas is C4F8The gas flow is 85sccm, the protective gas is introduced for 7 +/-1 s, the radio frequency power of the induction coil is 600W, and the induction coil is cycled once every 16-17 secondsAnd etching and protecting. The size of the needle point of the prepared micro-needle is less than 5 mu m, and the diameter of the bottom of the micro-needle is 150 mu m; the microneedles were 200 μm in height.
S5: and removing the silicon dioxide oxidation layer by a wet method, and removing the silicon dioxide oxidation layer and the photoresist on the top of the silicon substrate to obtain the silicon-based nano microneedle array for transdermal drug delivery.
Specifically, the volume ratio of hydrofluoric acid: ammonium fluoride: deionized water =3:6:10 solution corrodes the "cap" on top of the silicon substrate microneedle (i.e. the silicon dioxide oxide layer and the photoresist) to obtain the silicon substrate nano microneedle array for transdermal drug delivery.
The foregoing descriptions of specific exemplary embodiments of the present invention have been presented for purposes of illustration and description. It is not intended to limit the invention to the precise form disclosed, and obviously many modifications and variations are possible in light of the above teaching. The exemplary embodiments were chosen and described in order to explain certain principles of the invention and its practical application to enable one skilled in the art to make and use various exemplary embodiments of the invention and various alternatives and modifications as are suited to the particular use contemplated. It is intended that the scope of the invention be defined by the claims and their equivalents.

Claims (10)

1. A manufacturing process for a silicon-based nano microneedle array for transdermal drug delivery is characterized by comprising the following steps: the method comprises the following steps:
s1: depositing a silicon dioxide oxide layer on a silicon substrate;
s2: photoetching and developing, namely coating a layer of photoresist on the surface of the silicon dioxide oxide layer, covering the photoresist by using a mask plate with regularly distributed patterns for exposure, and then carrying out developing operation to form the patterns on the mask plate on the photoresist;
s3: wet etching, etching the silicon dioxide oxide layer which is not masked by the photoresist, and transferring the pattern on the photoresist to the silicon dioxide oxide layer;
s4: dry etching, namely etching the silicon substrate in a mode of etching while protecting to obtain a nano microneedle array structure with a narrow upper part and a wide lower part;
s5: and removing the silicon dioxide oxidation layer by a wet method, and removing the silicon dioxide oxidation layer and the photoresist on the top of the silicon substrate to obtain the silicon-based nano microneedle array for transdermal drug delivery.
2. The manufacturing process of the silicon-based nano microneedle array for transdermal drug delivery according to claim 1, is characterized in that: and in the S1, the silicon substrate with a polished single surface is selected, the thickness is 400-600 mu m, the silicon substrate is cleaned by acetone, ethanol and deionized water during deposition, then is dried by nitrogen, and then is deposited with a silicon dioxide oxide layer by a chemical vapor deposition (PECVD) method.
3. The manufacturing process of the silicon-based nano microneedle array for transdermal drug delivery according to claim 1, is characterized in that: the photoresist in the S2 is coated in a spin coating mode, the thickness is 1-1.5 mu m, and the photoresist is pre-dried for 5-10 minutes on a drying table at the temperature of 75-95 ℃ after being coated.
4. The manufacturing process of the silicon-based nano microneedle array for transdermal drug delivery according to claim 1, is characterized in that: and the exposure time in the step S2 is 6-10S, and the silicon substrate is placed into NaOH solution with the mass percent of 5% for development.
5. The manufacturing process of the silicon-based nano microneedle array for transdermal drug delivery according to claim 1, is characterized in that: hydrofluoric acid is adopted in the S3 during corrosion according to the volume ratio: ammonium fluoride: deionized water =3:6:10 mixed solution for etching.
6. The manufacturing process of the silicon-based nano microneedle array for transdermal drug delivery according to claim 1, is characterized in that: the etching and protecting mode in the S4 specifically comprises the following steps: etching gas is SF6, the flow is 130sccm, the etching time is 9 +/-1 s, and the radio frequency power of the induction coil is 600W; the protective gas is C4F8, the gas flow is 85sccm, the introduction time of the protective gas is 7 +/-1 s, and the radio frequency power of the induction coil is 600W; and (4) carrying out etching and protection once every 16-17 seconds.
7. The manufacturing process of the silicon-based nano microneedle array for transdermal drug delivery according to claim 1, is characterized in that: the microneedle tip size of the nanometer microneedle array structure with the narrow upper part and the wide lower part in the S4 is less than 5 μm, the diameter of the microneedle bottom is 50-150 μm, and the height of the microneedle is 50-200 μm.
8. The manufacturing process of the silicon-based nano microneedle array for transdermal drug delivery according to claim 1, is characterized in that: the shape of the microneedle bottom in the S4 is a circle, a square, an octagon or other polygons.
9. The manufacturing process of the silicon-based nano microneedle array for transdermal drug delivery according to claim 1, is characterized in that: the S5 adopts hydrofluoric acid in the volume ratio: ammonium fluoride: the mixed solution of deionized water =3:6:10 removes the silicon dioxide oxide layer and the photoresist.
10. The manufacturing process of the silicon-based nano microneedle array for transdermal drug delivery according to claim 1, is characterized in that: the photoresist is EPG533 photoresist.
CN202210257117.2A 2022-03-16 2022-03-16 Manufacturing process of silicon-based nano microneedle array for transdermal drug delivery Pending CN114590773A (en)

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WO2004112119A1 (en) * 2003-06-13 2004-12-23 Sumitomo Precision Products Co., Ltd. Method and apparatus for etching silicon and etched silicon body
JP2005199392A (en) * 2004-01-16 2005-07-28 Dainippon Printing Co Ltd Silicon needle and manufacturing method therefor
US20080051695A1 (en) * 2005-05-18 2008-02-28 Bai Xu High-aspect-ratio microdevices and methods for transdermal delivery and sampling of active substances
US20080157427A1 (en) * 2007-01-03 2008-07-03 Jin-Chern Chiou Method for fabricating microneedle array and method for fabricating embossing mold of microneedle array
CN106730309A (en) * 2016-12-19 2017-05-31 山东元旭光电股份有限公司 A kind of silicon micropin substrate and preparation method thereof
CN111228643A (en) * 2020-02-12 2020-06-05 成都工业学院 Hollow microneedle array device and manufacturing method thereof
CN114010934A (en) * 2021-11-29 2022-02-08 江苏大学 Local porous silicon micro-needle array and preparation method thereof

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6312612B1 (en) * 1999-06-09 2001-11-06 The Procter & Gamble Company Apparatus and method for manufacturing an intracutaneous microneedle array
WO2004112119A1 (en) * 2003-06-13 2004-12-23 Sumitomo Precision Products Co., Ltd. Method and apparatus for etching silicon and etched silicon body
JP2005199392A (en) * 2004-01-16 2005-07-28 Dainippon Printing Co Ltd Silicon needle and manufacturing method therefor
US20080051695A1 (en) * 2005-05-18 2008-02-28 Bai Xu High-aspect-ratio microdevices and methods for transdermal delivery and sampling of active substances
US20080157427A1 (en) * 2007-01-03 2008-07-03 Jin-Chern Chiou Method for fabricating microneedle array and method for fabricating embossing mold of microneedle array
CN106730309A (en) * 2016-12-19 2017-05-31 山东元旭光电股份有限公司 A kind of silicon micropin substrate and preparation method thereof
CN111228643A (en) * 2020-02-12 2020-06-05 成都工业学院 Hollow microneedle array device and manufacturing method thereof
CN114010934A (en) * 2021-11-29 2022-02-08 江苏大学 Local porous silicon micro-needle array and preparation method thereof

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