CN102526870A - Anomalous plane hollow microneedle based on surface micro processing process and preparation method thereof - Google Patents
Anomalous plane hollow microneedle based on surface micro processing process and preparation method thereof Download PDFInfo
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- CN102526870A CN102526870A CN2012100050302A CN201210005030A CN102526870A CN 102526870 A CN102526870 A CN 102526870A CN 2012100050302 A CN2012100050302 A CN 2012100050302A CN 201210005030 A CN201210005030 A CN 201210005030A CN 102526870 A CN102526870 A CN 102526870A
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- different plane
- microneedle
- hollow microneedle
- plane hollow
- micropin
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- 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
-
- 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
- A61M2037/003—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles having a lumen
-
- 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
Abstract
The invention discloses an anomalous plane hollow microneedle based on a surface micro processing process and a preparation method of the anomalous plane hollow microneedle. The method adopts a wet method etching process, an ultraviolet-lithographie -galanoformungand abformung (UV-LIGA) process and a casting process, the wet method etching is used for forming a needle point structure of the microneedle, the UV-LIGA is used for realizing the needle body part of the microneedle, and then, the microneedle structure with the hollow interior is formed by casting, so the anomalous plane hollow microneedle is realized. The anomalous plane hollow microneedle is formed through casting by a purpose-made mold, the expensive processing technology is not needed, the fast reproduction and the high-speed mass production can be realized, in addition, the wet method etching and the casting operation are relatively simple, and the whole set of technical process is simple and is easy to implement.
Description
Technical field
The present invention relates to a kind of empty micropin, be specifically related to a kind of different plane hollow microneedle based on surperficial fine process and preparation method thereof.
Background technology
People such as Chun had processed accurately to control biological substance have been injected into the silicon dioxide micropin in the cell in 1999.People such as Steber in 2000 processed can with the microneedle array of micropin syringe logotype.People such as Achim Trautmann had processed the microneedle array that contains liquid storage tank and microchannel in 2003.According to different processing technology, micropin is divided into different plane and isoplanar micropin, and the axle of isoplanar micropin is parallel to substrate, and the vertical and bottom surface of the axle of different plane micropin.Under the equal area situation, different plane micropin number is the micropin number much larger than the isoplanar, so most of micropin is all processed different plane micropin.Traditional different plane hollow microneedle method for preparing has combined deep reaction ion etching, isotropic etching and anisotropic lithographic technique.
Literature search through to prior art is found; J.G.E Gaedeniers etc. are at " Micro Electro Mechanical Systems " (MEMS), " Silicon micromachined hollow microneedles for transdermal liquid transfer " (based on the micro-machined empty micropin that is used for the fluid transfer medicine of silicon) delivered on the 15th ieee international conference in 2002, and the method for preparing of this article introduction is divided into 5 steps: 1, utilize RIE { generating deep hole on the 100} silicon chip; 2, utilize RIE to carve continuous hole overleaf; 3, adopt LPCVD at the silicon face deposited silicon nitride; 4, utilize anisotropic wet etch to prepare the needle point tip; 5, remove protective layer.
" based on the different plane hollow metal micro-needle of MEMS technology " that Shen Xiucheng etc. delivered in " sensing technology journal " 02 phase in 2009, the method for preparing of this article introduction has 3 steps: 1, utilize silicon (100) face lithographic technique on silicon chip, to etch down rectangular pyramid; 2, adopt electroplating technology to electroplate out hollow metal and fall rectangular pyramid; 3, leave fluid channel and remove remaining silicon from the back side.
There are several shortcomings in these 2 kinds of method for preparinies: 1, complicated steps is loaded down with trivial details; 2, manufacturing process relates to DRIE and electroplating technology, and is with high costs; 3, only on silicon, make microneedle configuration, the micropin height receives very big restriction; 4, be unfavorable for producing in enormous quantities.
Summary of the invention
The objective of the invention is to overcome the deficiency of prior art, proposed a kind of based on wet-etching technology and casting process different plane hollow microneedle that combine, simple relatively and preparation method thereof.
The present invention realizes through following technical scheme:
The method for preparing of the different plane hollow microneedle based on surperficial fine process of the present invention; This method adopts based on wet-etching technology, UV-LIGA technology and casting process; Wet etching is used to form the micropin needle point structure, and UV-LIGA is used to realize micropin needle body part, utilizes casting then; Form the microneedle configuration of an inner hollow, thereby realize out different plane hollow microneedle.
Said method of the present invention comprises the steps:
At first prepare a heavy doping p type polished silicon wafer as substrate, on silicon chip, get rid of the positive glue of one deck and the square pattern that develops in the above;
Utilize wet-etching technology then, remove the silicon oxide that comes out, obtain the silicon of the square pattern of silicon oxide lower floor;
Utilize wet-etching technology again, the silicon that exposes is carried out anisotropic etching, on silicon substrate, obtain the rectangular pyramid structure;
Then get rid of the negative glue of one deck again, and the micropin female mold structure of developing;
Metal-loaded silk array then, and with the liquid macroimolecule material it is cast;
Finally demould discharges different plane hollow microneedle structure.
Said wire array is to have a wire array of setting mechanical strength according to what required micropin height and size designed, so that produce the hollow lumen of micropin.
Said liquid macroimolecule material, employing be the biological friendly type and the easy macromolecular material of degraded.
Different plane hollow microneedle based on surperficial fine process of the present invention; Comprise that tool comprises having the rectangular pyramid needle point structure; Cylindrical needle body structure and hollow cylinder inner-cavity structure; The rectangular pyramid needle point structure is positioned on the cylindrical structural, and the hollow cylinder inner-cavity structure runs through whole needle point and needle body part.
Said have a rectangular pyramid needle point structure, and its inclination angle is 54.7 °.
Existing empty micropin mainly realizes through DRIE or electroplating technology, and is with high costs and micropin is height-limited.And the design that the present invention proposes is to utilize special die casting to form; Therefore the present invention compares with existing empty micropin method for preparing; Do not need expensive process technology; Can realize quick copy and produce in batches at a high speed, and wet etching and pouring operation are simple relatively, a whole set of technological process is simple.
Description of drawings
Fig. 1 is a different plane hollow microneedle sketch map in the embodiment of the invention.
Fig. 2 is a method for preparing flow chart in the embodiment of the invention.
The specific embodiment
Elaborate to inventive embodiment below in conjunction with accompanying drawing.The present invention provided detailed embodiment and concrete operating process, but protection scope of the present invention is not limited to following embodiment being to implement under the prerequisite with technical scheme of the present invention.
As shown in Figure 2, present embodiment comprises following step:
The first step: the p type boron-doping polished silicon wafer 4 that to prepare a crystal orientation be < 110>is as substrate.Get rid of the thick positive glue 2 of one deck 5 μ m above that, and photoetching development, mask plate is a square pattern.
Second step: utilize the HF wet-etching technology to remove the not silicon oxide 3 of covering place of positive glue.
The 3rd step: second step of KOH etching of mass fraction 30% is handled silicon chip later, obtain being inverted the rectangular pyramid structure.
The 4th step: get rid of the thick SU-8 glue 6 of one deck 300 μ m, and photoetching development, mask plate is a circular configuration.
The 5th step: in the negative mold that obtains, load molybdenum filament array board 5; This molybdenum filament array obtains through photoresist being carried out the photoetching development plating, and carries out the position correction process, can be exactly with the negative mold in the molybdenum filament alignment procedures four during loading; Molybdenum filament radius 30 μ m, length 600 μ m.
In the 6th step, the polystyrene (PS) 7 of casting at last after PS solidifies, carries out the demoulding and handles.
Microneedle configuration sketch map as shown in Figure 1, that present embodiment obtains, among the figure: micropin is divided into 2 parts up and down, and needle point and needle body, needle point are the rectangular pyramid structure, and the inclination angle is 54.7 °, and needle body is a cylindrical structural, micropin hollow, it is axial that hollow parts is parallel to micropin.
As shown in Figure 2, present embodiment comprises following step:
The first step: the p type boron-doping polished silicon wafer 4 that to prepare a crystal orientation be < 110>is as substrate.Get rid of the thick positive glue 2 of one deck 5 μ m above that, and photoetching development, mask plate is a square pattern.
Second step: utilize the HF wet-etching technology to remove the not silicon oxide 3 of covering place of positive glue.
The 3rd step: second step of KOH etching of mass fraction 30% is handled silicon chip later, obtain being inverted the rectangular pyramid structure.
The 4th step: get rid of the thick SU-8 glue 6 of one deck 200 μ m, and photoetching development, mask plate is a circular configuration.
The 5th step: in the negative mold that obtains, load molybdenum filament array board 5; This molybdenum filament array obtains through photoresist being carried out the photoetching development plating, and carries out the position correction process, can be exactly with the negative mold in the molybdenum filament alignment procedures four during loading; Molybdenum filament radius 30 μ m, length 600 μ m.
In the 6th step, the fusion polylactic acid (PLA) 7 of casting at last after PS solidifies, carries out the demoulding and handles.
Microneedle configuration sketch map as shown in Figure 1, that present embodiment obtains, among the figure: micropin is divided into 2 parts up and down, and needle point and needle body, needle point are the rectangular pyramid structure, and the inclination angle is 54.7 °, and needle body is a cylindrical structural, micropin hollow, it is axial that hollow parts is parallel to micropin.The micropin that present embodiment obtains is compared with embodiment 1, highly becomes short, and mechanical strength strengthens.
Be the preferred embodiments of the present invention more than, should be understood that the present invention also has other attainable modes, such as simple transformation parameter and the material selected for use etc., these are easy to realize for a person skilled in the art.
The present invention is based on wet-etching technology and casting process, does not need the process technology of complex and expensive, can duplicate in enormous quantities by quick and cheap carrying out, and wet etching is operated and pouring operation is simple relatively, and a whole set of technological process is simple.
Although content of the present invention has been done detailed introduction through above-mentioned preferred embodiment, will be appreciated that above-mentioned description should not be considered to limitation of the present invention.After those skilled in the art have read foregoing, for multiple modification of the present invention with to substitute all will be conspicuous.Therefore, protection scope of the present invention should be limited appended claim.
Claims (7)
1. the method for preparing based on the different plane hollow microneedle of surperficial fine process is characterized in that, comprises the steps:
At first prepare a heavy doping p type polished silicon wafer as substrate, on silicon chip, get rid of the positive glue of one deck and the square pattern that develops in the above;
Utilize wet-etching technology then, remove the silicon oxide that comes out, obtain the silicon of the square pattern of silicon oxide lower floor;
Utilize wet-etching technology again, the silicon that exposes is carried out anisotropic etching, on silicon substrate, obtain the rectangular pyramid structure;
Then get rid of the negative glue of one deck again, and the micropin female mold structure of developing;
Metal-loaded silk array then, and with the liquid macroimolecule material it is cast;
Finally demould discharges different plane hollow microneedle structure.
2. the method for preparing of the different plane hollow microneedle based on surperficial fine process according to claim 1; It is characterized in that; Said wire array is to have a wire array of setting mechanical strength according to what required micropin height and size designed, so that produce the hollow lumen of micropin.
3. the method for preparing of the different plane hollow microneedle based on surperficial fine process according to claim 1 is characterized in that, said liquid macroimolecule material, employing be the biological friendly type and the macromolecular material of degraded easily.
4. according to the method for preparing of each described different plane hollow microneedle based on surperficial fine process of claim 1-3, it is characterized in that practical implementation is following:
The first step: the p type boron-doping polished silicon wafer that to prepare a crystal orientation be < 110>is got rid of the positive glue of one deck above that as substrate, and photoetching development, and mask plate is a square pattern;
Second step: utilize the HF wet-etching technology to remove the not silicon oxide of covering place of positive glue;
The 3rd step: second step of KOH etching of mass fraction 30% is handled silicon chip later, obtain being inverted the rectangular pyramid structure;
The 4th step: get rid of one deck SU-8 glue, and photoetching development, mask plate is a circular configuration;
The 5th step: in the negative mold that obtains, load the molybdenum filament array board, this template was carried out the position correction process;
In the 6th step, casting polystyrene or fusion polylactic acid after solidifying, carry out the demoulding and handle, and discharge different plane hollow microneedle structure.
5. different plane hollow microneedle that obtains according to the said method of claim 1-4; It is characterized in that; Comprise and have the rectangular pyramid needle point structure; Cylindrical needle body structure and hollow cylinder inner-cavity structure, the rectangular pyramid needle point structure is positioned on the cylindrical structural, and the hollow cylinder inner-cavity structure runs through whole needle point and needle body part.
6. different plane hollow microneedle according to claim 5 is characterized in that, said have a rectangular pyramid needle point structure, and its inclination angle is 54.7 °.
7. according to claim 5 or 6 described different plane hollow microneedles, it is characterized in that it is axial that the hollow parts of hollow cylinder inner-cavity structure is parallel to micropin.
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Cited By (8)
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| CN104057564A (en) * | 2014-06-06 | 2014-09-24 | 游学秋 | Micro-needle making method based on inclined casting mould |
| CN104117137A (en) * | 2014-07-08 | 2014-10-29 | 清华大学 | Capsule type hollow medicine loading micro-needle array and producing method thereof |
| WO2018198675A1 (en) * | 2017-04-27 | 2018-11-01 | シンクランド株式会社 | Microneedle production method |
| CN108751120A (en) * | 2018-04-13 | 2018-11-06 | 杭州电子科技大学 | A kind of preparation method of silicon substrate microneedle array patch |
| CN109332831A (en) * | 2018-11-20 | 2019-02-15 | 广东工业大学 | A kind of micro- texture processing unit (plant) in surface |
| CN109771812A (en) * | 2019-01-21 | 2019-05-21 | 北京化工大学 | Soluble Fiber is the method that the ultra-violet curing technique of core material prepares empty micropin |
| CN110279935A (en) * | 2019-07-11 | 2019-09-27 | 上海揽微医学科技有限公司 | Prismatic silicon micropin and preparation method thereof |
| CN113443603A (en) * | 2021-06-30 | 2021-09-28 | 苏州恒之清生物科技有限公司 | Preparation method of superfine hollow microneedle chip |
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| US20030009113A1 (en) * | 2001-07-09 | 2003-01-09 | Lorin Olson | Micro-needles and methods of manufacture and use thereof |
| WO2004062899A2 (en) * | 2003-01-16 | 2004-07-29 | Seung-Seob Lee | Method for manufacturing of polymer micro needle array with liga process |
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Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104057564A (en) * | 2014-06-06 | 2014-09-24 | 游学秋 | Micro-needle making method based on inclined casting mould |
| CN104057564B (en) * | 2014-06-06 | 2016-08-03 | 游学秋 | Based on the micropin manufacture method tilting mold |
| CN104117137A (en) * | 2014-07-08 | 2014-10-29 | 清华大学 | Capsule type hollow medicine loading micro-needle array and producing method thereof |
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| JP6421393B1 (en) * | 2017-04-27 | 2018-11-14 | シンクランド株式会社 | Manufacturing method of microneedle |
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| CN108751120A (en) * | 2018-04-13 | 2018-11-06 | 杭州电子科技大学 | A kind of preparation method of silicon substrate microneedle array patch |
| CN109332831A (en) * | 2018-11-20 | 2019-02-15 | 广东工业大学 | A kind of micro- texture processing unit (plant) in surface |
| CN109332831B (en) * | 2018-11-20 | 2019-11-19 | 广东工业大学 | A kind of micro- texture processing unit (plant) in surface |
| CN109771812A (en) * | 2019-01-21 | 2019-05-21 | 北京化工大学 | Soluble Fiber is the method that the ultra-violet curing technique of core material prepares empty micropin |
| CN110279935A (en) * | 2019-07-11 | 2019-09-27 | 上海揽微医学科技有限公司 | Prismatic silicon micropin and preparation method thereof |
| CN110279935B (en) * | 2019-07-11 | 2022-01-07 | 上海揽微医学科技有限公司 | Prismatic silicon microneedle and preparation method thereof |
| CN113443603A (en) * | 2021-06-30 | 2021-09-28 | 苏州恒之清生物科技有限公司 | Preparation method of superfine hollow microneedle chip |
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