CN100441388C - Microneedle preparation method based on multiplayer processing technology - Google Patents
Microneedle preparation method based on multiplayer processing technology Download PDFInfo
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- CN100441388C CN100441388C CNB2006100254677A CN200610025467A CN100441388C CN 100441388 C CN100441388 C CN 100441388C CN B2006100254677 A CNB2006100254677 A CN B2006100254677A CN 200610025467 A CN200610025467 A CN 200610025467A CN 100441388 C CN100441388 C CN 100441388C
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- microneedle
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Abstract
The present invention relates to a microneedle making method of the technical field of micro-fine processing based on a multi-layer processing technique, which has steps: (1) a titanium film is sedimentated, and oxidation treatment is carried out; (2) SU-8 negative glue is swung, exposure is carried out after well prebaking, midbaking, development, electroplating, mechanical grinding and polishing are carried out, and the first layer of the metallic structure of a needed thickness is obtained; (3)metallic activating treatment is carried out on the surface after being polished; (4) a step (2) and a step (3) are repeated till the last layer of photoresist is swung, electroforming is carried out after the prebaking, the exposure, the midbaking and the development of the last layer of the photoresist are completed, and a metallic mould for moulding is obtained by removing the photoresist after the electroforming is completed; (5) the hot press and the copy of a polymer are carried out on the metallic mould; (6) after the back part of the polymer is thinly cut, a microneedle of a through hole is obtained by demoulding the polymer. The present invention can realize mass microneedle processing with low cost, a material range suitable for processing is wide, and microneedle structures with different stair side surfaces and height can be obtained by adjusting the outside diameter tolerance and the layer number of layers only.
Description
Technical field
The present invention relates to the method in a kind of Micrometer-Nanometer Processing Technology field, particularly a kind of microneedle preparation method based on multiplayer processing technology.
Background technology
Traditional hypodermic injection generally need allow syringe needle transdermal top layer and going deep into below the skin, so that directly medicine is sent into blood vessel.Therefore this process not only is accompanied by pain, and injection technique need be accepted certain training and could grasp.And microneedle only pierces through the skin surface cuticula and no longer deep, and medicine enters blood circulation system by capillary.Owing to do not contain nerve endings in the cuticula, can not feel obvious pain in the injection process.The operating process of miniature syringe needle is also very simple, need only directly needle array be sticked skin and get final product, and is specially adapted to the efficient medicine of low dose of injection.
The micropin of report research at present mainly contains three kinds of methods.The one, adopt silicon technology, by wet etching or reactive ion etching technology machine silicon microprobe, the 2nd, utilize processes metal micro-needles such as Laser Processing, plating and wet etching, there is complex process in above-mentioned two kinds of methods, process-cycle is long, the shortcoming that cost is high all is difficult to satisfy the biomedical last requirement of using.The 3rd, people such as Jung-Hwan Park are at the article of last the 371st page to the 374th page " MicromachinedBiodegradable Microstructures " (little processing biodegradable micro-structural) by name of delivering of the 16th annualinternational conference on micro electro mechanical systems (meeting of the 16 MOEMS International Year) in 2003, the SU-8 photoresist of introducing in this article that utilizes prepares the microneedle configuration mother matrix, copy the PDMS mould then, utilize this mould biodegradable microprobe of casting again.Though this method can realize the mass production of microprobe, but because the PDMS material is very soft, duplicate micropin with it and can only adopt casting method, therefore it is longer than the mould pressing process that metal die adopted required process time to duplicate micropin with it, and suitable PDMS mould comes material processed also to lack than metal die.
Summary of the invention
The objective of the invention is to overcome deficiency of the prior art, a kind of microneedle preparation method based on multiplayer processing technology is provided, adopt multiplayer processing technology and UV-LIGA technology, electroforming obtains the metal die with the ladder side, but with this mould polymer micro needle of batch duplicating band ladder side just, thus this processing method not only to have technology simple, process cycle is short, the advantage that cost is low has the advantage that is easy to process different top structure micropins simultaneously.
The present invention is achieved by the following technical solutions, and concrete steps of the present invention are as follows:
1) titanium deposition film, and make oxidation processes.Adhesion between the photoresist that the selection of metal material will take into full account and get rid of later, the present invention adopts Titanium, and oxide treatments is to improve the adhesion of itself and photoresist.
2) get rid of the SU-8 photoresist, expose after preceding baking is good, middle baking, development, plating and mechanical lapping and polishing (obtaining the metal structure of ground floor desired thickness).
3) the metal activation processing is done on the surface after the polishing, removes surface oxide layer to guarantee the adhesion between the multiple layer metal.
4) design according to microneedle configuration, repeat the 2nd) and the 3rd) go on foot until getting rid of last layer photoetching glue, with preceding which floor different be: last layer photoetching glue finishes preceding baking, exposure, middle baking, what carry out after developing is electroforming, and finishing removes photoresist after the electroforming just obtains the metal die that can use for mold pressing.
5) metal die carries out polymer hot pressing and duplicates.
6) micropin that the thin back demoulding obtains through hole is cut at the polymer back.
The present invention utilizes the multiplayer processing technology electroforming to obtain metal die with the ladder side, with this mould polymer micro needle of batch duplicating band ladder side again.The mould metal is nickel, iron-nickel alloy or copper, and this mould structure has the advantage that is convenient in demoulding.
The external diameter of micropin and the diameter of bore of micropin are by mask size decision on the lithography mask version, and the mask size just obtains the micropin of various outer diameter and diameter of bore on the change mask version, and micropin can be single, also can be array.The length of micropin is decided by the photoresist gross thickness.Therefore this method is applicable to the micropin of processing different length.
The present invention utilizes multiplayer processing technology to obtain microneedle configuration with the ladder side, so the external diameter that this method only need be adjusted between the sandwich construction is poor, the corresponding micropin that just can obtain different ladder side structures.Micropin top structure of the present invention in the end relies on during a layer photoetching plane process technology just can realize.
The polymer that the present invention duplicates is plastics or rubber, duplicates the method that the plastics micropin adopts mold pressing, duplicates the method that the rubber micropin adopts casting.
Among the present invention, because required time of electroforming mould is longer, so preferentially adopt the little stress electroforming process of low speed.Adopt the solvent of removing photoresist to remove photoresist.
The present invention adopts multiplayer processing technology to process metal die, duplicate the method for micropin then and process micropin, so it is a kind of micropin processing method of mass, processing cost is low, different with existing process technology in addition is: (1) because the micropin mould that the processing of this technology obtains is a metal material, not only die life long, and suit to come the material processed scope wideer with this technology, both can be used to the moulded plastic base polymer, also can be used to the rubber polymer of casting.(2) utilize multiplayer processing technology obtaining the microneedle configuration of ladder side, so this method outside diameter tolerance that only need adjust each layer and the number of plies just can obtain the microneedle configuration of different ladders side.(3) length of micropin is by the gross thickness decision of photoresist.(4) top structure of micropin is by last layer mask version design decision.
The specific embodiment
Particular content below in conjunction with the inventive method provides embodiment:
At first the Titanium that deposits 2 microns on silicon chip is done Seed Layer, carry out oxidation processes then, concrete oxidation technology is: the NaOH of 15 grams is dissolved in the deionized water of 750ml, for improving oxidation rate and oxidation uniformity, oxidation is carried out in 65 ℃ of water-baths, when the water-bath temperature reaches 50 ℃, add the 15ml hydrogen peroxide, when the water-bath temperature reaches 65 ℃ substrate is put into, three minutes finish oxidation, put into deionized water then and clean substrate.
Get rid of 50 microns SU-8 photoresists on oxidation and the substrate that cleans up, carry out preceding baking then, preceding baking condition is: 65 ℃ of baking half an hour, 95 ℃ of bakings were cooled off with stove after 15 minutes.The good substrate of preceding baking exposes, and conditions of exposure is: 450mJ/cm
2Substrate after the exposure carries out the back baking, and back baking condition is: 65 ℃ are dried by the fire half an hour, and 90 ℃ of bakings were cooled off with stove after 10 minutes.The substrate that the back baking is good develops, and development conditions is 6 minutes.
Plated metal nickel on the good substrate that develops, the condition of plating is: electroforming solution pH value 5,50 ℃ of temperature, the quality of electroforming metal was better when electroforming speed was controlled at 14 microns/hour.
When surpassing photoresist thickness, the thickness of plated metal carries out abrasive disc, to grind good substrate activation processing then, substrate after the processing gets rid of 50 microns SU-8 photoresists of the second layer, repeat then preceding baking, exposure, after dry by the fire, develop, electroplate, polish, activation processing, then get rid of the 3rd layer of 50 microns SU-8 photoresist, repeat then preceding baking, exposure, after dry by the fire, develop, electroplate, polish, activation processing, get rid of the 4th layer of 50 microns SU-8 photoresist then, repeat preceding baking, exposure, back baking then, the back electroforming of developing becomes mould.
The removal of solvents that spends SU-8 glue is embedded in the photoresist in the mould.
With nickel mould compacting PC material micropin, the mold pressing parameter of employing is: 200 ℃ of molding temperatures, molding pressure 5000N, clamp time 60S, 120 ℃ of calcining temperatures, stripping rate 0.2 (mm/s).
The present invention adopts multiplayer processing technology to process metal die, duplicate the method for micropin then and process micropin, so it is a kind of micropin processing method of mass, processing cost is low, because the micropin mould that the processing of this technology obtains is a metal material, not only die life long, and suit to come the material processed scope wideer with this technology, both can be used to the moulded plastic base polymer, also can be used to the rubber polymer of casting.
Utilize multiplayer processing technology can obtain the microneedle configuration of ladder side easily, so this method outside diameter tolerance that only need adjust each layer and the number of plies just can obtain the microneedle configuration of different ladders side and height.
Claims (6)
1, a kind of microneedle preparation method based on multiplayer processing technology is characterized in that, comprises the steps:
1) titanium deposition film, and make oxidation processes;
2) get rid of the SU-8 photoresist, expose after preceding baking is good, middle baking, development, plating and mechanical lapping and polishing, obtain the metal structure of ground floor desired thickness;
3) the metal activation processing is done on the surface after the polishing;
4) repeat the 2nd) with the 3rd) step is until getting rid of last layer photoetching glue, last layer photoetching glue finishes preceding baking, exposure, middle baking, carry out electroforming after developing, and finishing removes photoresist after the electroforming obtains the metal die used for mold pressing;
5) metal die carries out polymer hot pressing and duplicates;
6) micropin that the thin back demoulding obtains through hole is cut at the polymer back.
2, the microneedle preparation method based on multiplayer processing technology according to claim 1 is characterized in that, described metal die is the metal die of band ladder side, and the mould metal is nickel, iron-nickel alloy or copper.
3, the microneedle preparation method based on multiplayer processing technology according to claim 1, it is characterized in that, the external diameter of micropin and the diameter of bore of micropin are by mask size decision on the lithography mask version, and micropin is single or array, and the length of micropin is decided by the photoresist gross thickness.
According to claim 1 or 3 described microneedle preparation methods, it is characterized in that 4, the outside diameter tolerance of adjusting each layer just obtains different ladders side and microneedle configuration highly with the number of plies based on multiplayer processing technology.
5, the microneedle preparation method based on multiplayer processing technology according to claim 1 is characterized in that, described polymer is plastics or rubber.
6, the microneedle preparation method based on multiplayer processing technology according to claim 1 is characterized in that, the little stress electroforming process of low speed is adopted in described electroforming.
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| Application Number | Priority Date | Filing Date | Title |
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| CNB2006100254677A CN100441388C (en) | 2006-04-06 | 2006-04-06 | Microneedle preparation method based on multiplayer processing technology |
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| CNB2006100254677A CN100441388C (en) | 2006-04-06 | 2006-04-06 | Microneedle preparation method based on multiplayer processing technology |
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| CN1864976A CN1864976A (en) | 2006-11-22 |
| CN100441388C true CN100441388C (en) | 2008-12-10 |
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Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100579599C (en) * | 2008-04-09 | 2010-01-13 | 南京大学 | Preparation of micro-needle array injection syringe |
| CN101297989B (en) * | 2008-06-19 | 2010-06-23 | 上海交通大学 | Batch preparation of hollow micro-needle based on molding |
| CN101342404B (en) * | 2008-08-28 | 2010-04-14 | 上海交通大学 | Method for manufacturing different-plane metal hollow fine needle for transdermal drug administration |
| CN101347652B (en) * | 2008-09-09 | 2011-01-12 | 南京大学 | Method for preparing hollow micro-needle array injection syringe |
| CN102175840A (en) * | 2010-12-30 | 2011-09-07 | 北京大学 | Whole blood centrifugal separation chip and preparation method thereof |
| CN102139138A (en) * | 2011-03-22 | 2011-08-03 | 上海交通大学 | Preparation method of solid metal microneedle array |
| CN102320559B (en) * | 2011-09-14 | 2014-06-18 | 上海交通大学 | Preparation method of hollow-structured micro-array electrode |
| EP2767869A1 (en) * | 2013-02-13 | 2014-08-20 | Nivarox-FAR S.A. | Method for manufacturing a one-piece micromechanical part comprising at least two separate levels |
| CN109364366A (en) * | 2018-09-21 | 2019-02-22 | 华中科技大学 | Template prepares the method and its application of porous polymer micropin |
| CN111467667B (en) * | 2020-04-17 | 2020-12-04 | 南京鼓楼医院 | Multilayer microneedle array and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1425062A2 (en) * | 2001-09-05 | 2004-06-09 | 3M Innovative Properties Company | Microneedle arrays and methods of manufacturing the same |
| CN1526454A (en) * | 2003-03-06 | 2004-09-08 | 财团法人工业技术研究所 | Manufacture of micro syringe array |
| CN1555893A (en) * | 2003-12-30 | 2004-12-22 | 上海交通大学 | Method of bulk processing micro probe based on three dimensional micro processing technology |
| WO2005087305A1 (en) * | 2004-03-12 | 2005-09-22 | Agency For Science, Technology And Research | Methods and moulds for use in fabricating side-ported microneedles |
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- 2006-04-06 CN CNB2006100254677A patent/CN100441388C/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1425062A2 (en) * | 2001-09-05 | 2004-06-09 | 3M Innovative Properties Company | Microneedle arrays and methods of manufacturing the same |
| CN1526454A (en) * | 2003-03-06 | 2004-09-08 | 财团法人工业技术研究所 | Manufacture of micro syringe array |
| CN1555893A (en) * | 2003-12-30 | 2004-12-22 | 上海交通大学 | Method of bulk processing micro probe based on three dimensional micro processing technology |
| WO2005087305A1 (en) * | 2004-03-12 | 2005-09-22 | Agency For Science, Technology And Research | Methods and moulds for use in fabricating side-ported microneedles |
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