CN104503207A - Method for manufacturing hollow microneedle array with conical top - Google Patents
Method for manufacturing hollow microneedle array with conical top Download PDFInfo
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- CN104503207A CN104503207A CN201410733926.1A CN201410733926A CN104503207A CN 104503207 A CN104503207 A CN 104503207A CN 201410733926 A CN201410733926 A CN 201410733926A CN 104503207 A CN104503207 A CN 104503207A
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- microneedle
- conical top
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Abstract
The invention discloses a method for manufacturing a hollow microneedle array with a conical top. Photoresist of different photosensitizer concentrations is mixed to prepare a series of photoresist of single or more photosensitizer concentrations, only if the photosensitiveness of upper-layer photoresist is higher than that of lower-layer photoresist when used, by virtue of the difference of the photoresist in exposure dose, the upper-layer photoresist does not affect the structure of the lower-layer photoresist when the exposure dose is precisely controlled, so that a complex microneedle structure can be obtained through multiple times of exposure and once development. Not only is the microneedle manufactured by using the hollow microneedle manufacturing process disclosed by the invention good in structure and simple in process, but also the overall quality of the hollow microneedle array is further ensured as a microneedle channel is formed through laser punching after being manufactured, so that the hollow microneedle array is wide in applicability. The operation of depositing a parylene biological compatible membrane is simple and feasible, and moreover the biocompatibility is improved as a whole; a micro-fluid system consisting of the integrated hollow microneedle arrays and micro-fluidic chips has wide application in the field of percutaneous diagnosis and treatment.
Description
Technical field
What the present invention relates to is a kind of technology of micropin preparation field, specifically a kind of empty micropin array preparation method of conical top.
Background technology
Micropin is diameter is tens microns, the acicular texture of length more than 100 microns.Micropin is widely used at biomedical sector.Adopt microneedle transdermal delivery or sampling, not only there is trace, painless feature, and the precision of biochemical investigation, reliability and efficiency can be made to increase substantially.Microfluid in empty micropin and MEMS, micro-analysis system combine, and can realize microminiaturization that biochemistry detection analyzes and integrated
Micropin action mode is various.Utilize solid array of microneedles to thrust skin, form microchannel at skin surface, then shift out micropin, then medicine paste is overlying on the skin surface forming microchannel.This mode is one action mode the most widely, but micropin removes that rear Micro-v oid is closed gradually and difference on different molecular weight the permeation rate of drugs causes the transdermal penetration of different pharmaceutical to there is larger difference; Biodegradable material is adopted to prepare micropin.In the preparation drug molecule and micropin material are pre-mixed aftershaping, after micropin acts on skin with micropin material degraded release medicine, but medicine with micropin material in the lump shaping again to it bring micropin moulding process on the impact of pharmaceutical properties and medicine the long term stability problem in needle body material; Microfluid in empty micropin and MEMS, micro-analysis system combine, the microminiaturization and integrated that biochemistry detection is analyzed can be realized, but this difficulty on manufacturing of empty micropin and application upper must and the Combination application of the complex micro structure such as Micropump, micro-valve further increase system manufacture difficulty and manufacturing cost, therefore the technical advantage of empty micropin on percutaneous dosing is applied directly is subject to its restriction preparing difficulty.
The basic reason of empty micropin preparation difficulty is: the yardstick of three dimensional micron level constructs empty micropin passage.Because yardstick is small, complex structure, is not only difficult to be copied by revolving die, even if can pass through the structure that the means such as repeatedly photoetching can realize needs, its total quality is also difficult to ensure.
Through finding the retrieval of prior art, Po ?Chun Wang within 2013, be published in JOURNAL OFMICROELECTROMECHANICAL SYSTEMS, VOL.22, the article of the Fabrication andCharacterization of Polymer Hollow Microneedle Array Using UV Lithography Into Micromolds by name on NO.5, describe SU ?the preparation method of 8 glue empty micropin arrays.Whole SU ?8 structure constructions above PDMS, PDMS not only as substrate and also have concurrently mould use, due to its thickness thicker and and soft, so exist himself flatness be difficult to ensure problem, the direct consistance affecting photoresist micropin height, and hard photoresist structure is coated with on soft base material, the contraction etc. during photoresist solidification will cause the warpage of total.In addition, it is also that difficulty is very large that hollow passageway structure relies on development to realize, although therefore the preparation method of this article proposition is feasible, total quality is difficult to guarantee.
Summary of the invention
The present invention is directed to prior art above shortcomings, propose a kind of empty micropin array preparation method of conical top, by being directly coated on mask graph by photoresist, exposing the coniform hollow-core construction obtained; By the reasonable utilization of different photosensitivity photoresist, the difference in both utilizations photosensitivity, realizes the exposure of upper strata photoresist to bottom photoresist structure without impact, meets the application demand of microneedle transdermal delivery.
The present invention is achieved by the following technical solutions:
The present invention relates to a kind of empty micropin array preparation method of conical top, single or prepare the different middle lithography layer of the photosensitivity of multiple modification successively with preparation after the mixing of the photoresist of two kinds of different models, and adopt the high photoresist of photosensitivity to prepare top lithography layer at top, make finally by laser boring.
Described different model is preferably without SU ?850 and the general commercial SU ?8100 of photosensitizer, and its blending ratio is according to applying the assembly adhesive characteristic and thickness requirement determination weight ratio that adopt.
Described middle lithography layer is prepared by following steps:
1) photoresist of two kinds of different models is fully stirred, stand-by after eliminating bubble;
2) glue whirl coating step 1 prepared, front baking obtain the smooth photoresist of 200 ~ 400 micron thickness;
3) middle baking rear-inclined is rotated exposure 20 ~ 30 minutes.
Any angle of angle for being less than 90 degree of described Sloped rotating, is preferably 18o.
Described photoresist meets the biocompatibility requirement of application further by non-biocompatible thin film such as deposition parylene.
Described top lithography layer is prepared by following steps:
I) on middle lithography layer, get rid of the photoresist of single model, front baking obtains the smooth photoresist of 400 micron thickness.
Ii) after drying in, Regular contact exposes 200 seconds.
Iii) develop 2 hours.
Described front baking refers to: heat 5 hours at 90 DEG C.
Described middle baking refers to: heat 2 hours at 90 DEG C.
Its applicability the method such as sedimentary organism compatibility material to its surface modification, can be improved further in the surface of described empty micropin array.
The present invention relates to the empty micropin array of the conical top that said method prepares, its top structure is circular cone and the angle of inclination that circular cone drift angle is exposed by described Sloped rotating regulates, the pitch angle of its circular cone drift angle=2* Sloped rotating exposure.
The present invention relates to the application of the empty micropin array of above-mentioned conical top, use it for integrated with micro-fluidic chip and prepare microfluid system.
Technique effect
Compared with prior art, simple, the flow process of present invention process improves crudy and reliability while shortening.
Accompanying drawing explanation
Fig. 1 is the structural representation of micropin of the present invention before laser boring.
Fig. 2 is the structural representation of micropin of the present invention after laser boring.
Embodiment
Elaborate to embodiments of the invention below, the present embodiment is implemented under premised on technical solution of the present invention, give detailed embodiment and concrete operating process, but protection scope of the present invention is not limited to following embodiment.
Embodiment 1
The present embodiment comprises the following steps:
The first step, select and mix with the weight ratio of 1:20 without the SU ?850 of photosensitizer and general commercial SU ?8100, through fully stirring, stand-by after eliminating bubble.
Second step, the glue whirl coating first step prepared, front baking obtain the smooth photoresist of 300 micron thickness.
3rd step, middle baking rear-inclined rotate exposure 30 minutes.
4th step, get rid of on ground floor photoresist SU ?8100, front baking obtains the smooth photoresist of 400 micron thickness.
After 5th step, middle baking, Regular contact exposes 200 seconds.
6th step, development 1 hour.
7th step, laser boring.
What the present embodiment was prepared is substrate thickness 400 microns, the conical empty micropin array of height 300 microns.
Embodiment 2
The present embodiment comprises the following steps:
The first step, select and mix with the weight ratio of 1:10 without the SU ?850 of photosensitizer and SU ?8100, through fully stirring, stand-by after eliminating bubble.
Second step, the glue whirl coating first step prepared, front baking obtain the smooth photoresist of 400 micron thickness.
3rd step, middle baking rear-inclined rotate exposure 20 minutes.
4th step, get rid of on ground floor photoresist SU ?8100, front baking obtains the smooth photoresist of 400 micron thickness.
After 5th step, middle baking, Regular contact exposes 200 seconds.
6th step, development 1 hour.
7th step, laser boring.
8th step, deposition parylene film, improve biocompatibility.
What the present embodiment was prepared is substrate thickness 400 microns, the conical empty micropin array of height 400 microns.
Embodiment 3
The present embodiment comprises the following steps:
The first step, select and mix with the weight ratio of 1:40 without the SU ?850 of photosensitizer and SU ?8100, through fully stirring, stand-by after eliminating bubble.
Second step, the glue whirl coating first step prepared, front baking obtain the smooth photoresist of 200 micron thickness.
3rd step, middle baking rear-inclined rotate exposure 25 minutes.
4th step, select and mix with the weight ratio of 1:20 without the SU ?850 of photosensitizer and SU ?8100, through fully stirring, stand-by after eliminating bubble.
5th step, the glue whirl coating the 4th step prepared, front baking obtain the smooth photoresist of 200 micron thickness.
After 6th step, middle baking, Regular contact exposes 100 seconds.
7th step, get rid of on the second layer photoresist SU ?8100, front baking obtains the smooth photoresist of 400 micron thickness.
After 8th step, middle baking, Regular contact exposes 200 seconds.
9th step, development 2 hours.
Tenth step, laser boring.
11 step, deposition parylene film, improve biocompatibility.
What the present embodiment was prepared is substrate thickness 400 microns, the empty micropin array of the top conical of cone height 200 microns, cylinder height 200 microns.
As shown in Figure 1,1 and 2 is the photoresists seeing light, and wherein 1 is the part of seeing light all the time, and the present invention's marked improvement is compared to existing technology:
A. photoresist is directly coated on mask graph, exposes the coniform hollow-core construction but not common revolving die circular cone mould that obtain;
B. by the reasonable utilization of different photosensitivity photoresist, the difference in both utilizations photosensitivity, realizes upper strata photoresist exposure to bottom photoresist structure without impact.
Not only structure 3 exposes on 1 and 2 structures without impact, and the development of routine just can play the effect of structure release.Such combination new design could realize the empty micropin array novel preparation method of conical top.The microneedle substrate of coniform microneedle configuration and tape channel is once developed by multiexposure, multiple exposure and obtains.Development not only realizes desired structure, and whole photoresist structure is able to discharge from substrate.Obtain the micropin passage of required yardstick finally by laser boring, meet the application demand of microneedle transdermal delivery.
Claims (9)
1. the empty micropin array preparation method of a conical top, it is characterized in that, single or prepare the different middle lithography layer of the photosensitivity of multiple modification successively with preparation after the mixing of the photoresist of two kinds of different models, once to be developed the complicated microneedle configuration of preparation by multiexposure, multiple exposure according to the photosensitivity of the upper strata photoresist principle of design higher than lower floor, make finally by laser boring.
2. method according to claim 1, is characterized in that, described different model refers to: without the SU-8 sequence of photolithography glue of photosensitizer and containing photosensitizer SU-8 sequence of photolithography glue.
3. method according to claim 1, is characterized in that, described middle lithography layer is prepared by following steps:
1) photoresist of two kinds of different models is fully stirred, stand-by after eliminating bubble;
2) glue whirl coating step 1 prepared, front baking obtain the smooth photoresist of thickness;
3) dry in after Sloped rotating exposure.
4. method according to claim 3, is characterized in that, the angle of described Sloped rotating is be less than the random angle of 90 degree.
5. method according to claim 1, is characterized in that, described photoresist meets biocompatibility requirement further by non-biocompatible thin film such as deposition parylene.
6. method according to claim 3, is characterized in that, described front baking refers to: heat 5 hours at 90 DEG C.
7. method according to claim 3, is characterized in that, described middle baking refers to: heat 2 hours at 90 DEG C.
8. the empty micropin array of the conical top that method prepares according to above-mentioned arbitrary claim, it is characterized in that, its top structure is circular cone and the degree of tilt that tapering is exposed by described Sloped rotating regulates, the pitch angle of its circular cone drift angle=2* Sloped rotating exposure.
9. the application according to the empty micropin array of the conical top described in above-mentioned arbitrary claim, it is characterized in that, using it for the integrated formation microfluid system with micro-fluidic chip to can be used for sampling, analyze and detecting, is a kind of new and effective high reliability disease treatment technology.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105334697A (en) * | 2015-12-08 | 2016-02-17 | 深圳市华星光电技术有限公司 | Photoresist composition and method for manufacturing color filter |
| CN107569238A (en) * | 2016-07-04 | 2018-01-12 | 中山大学 | A kind of adhesive type chimney type microneedle array and its manufacture method |
| CN107872993A (en) * | 2016-07-25 | 2018-04-03 | 新信心股份有限公司 | Micropin manufacture method and micropin manufacture device |
| CN109125912A (en) * | 2018-08-09 | 2019-01-04 | 武汉大学 | A kind of 3D printing microneedle patch and preparation method thereof that Intelligent blood sugar is adjusted |
| CN113977829A (en) * | 2021-09-08 | 2022-01-28 | 北京宝理泰科技有限公司 | Preparation method of hollow microneedle array biosensor |
| EP4091022A4 (en) * | 2020-01-16 | 2024-02-07 | Univ Kansas State | Microneedle, microcone, and photolithography fabrication methods |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US20060084942A1 (en) * | 2004-10-15 | 2006-04-20 | Board Of Regents, The University Of Texas System | Tapered hollow metallic microneedle array assembly and method of making and using the same |
-
2014
- 2014-12-04 CN CN201410733926.1A patent/CN104503207B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060084942A1 (en) * | 2004-10-15 | 2006-04-20 | Board Of Regents, The University Of Texas System | Tapered hollow metallic microneedle array assembly and method of making and using the same |
Non-Patent Citations (3)
| Title |
|---|
| PO-CHUN WANG ET AL.: "Fabrication and characterization of polymer hollow microneedle array using UV lithography into micromolds", 《JOURNAL OF MICROELECTROMECHANICAL SYSTEMS》 * |
| 曹玉田: "微针的制备与应用研究", 《中国优秀硕士学位论文全文数据库》 * |
| 蒋宏民: "MEMS微针制备技术及其工艺研究", 《中国优秀硕士学位论文全文数据库》 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105334697A (en) * | 2015-12-08 | 2016-02-17 | 深圳市华星光电技术有限公司 | Photoresist composition and method for manufacturing color filter |
| CN107569238A (en) * | 2016-07-04 | 2018-01-12 | 中山大学 | A kind of adhesive type chimney type microneedle array and its manufacture method |
| CN107872993A (en) * | 2016-07-25 | 2018-04-03 | 新信心股份有限公司 | Micropin manufacture method and micropin manufacture device |
| CN107872993B (en) * | 2016-07-25 | 2020-01-21 | 新信心股份有限公司 | Microneedle manufacturing method and microneedle manufacturing apparatus |
| CN109125912A (en) * | 2018-08-09 | 2019-01-04 | 武汉大学 | A kind of 3D printing microneedle patch and preparation method thereof that Intelligent blood sugar is adjusted |
| EP4091022A4 (en) * | 2020-01-16 | 2024-02-07 | Univ Kansas State | Microneedle, microcone, and photolithography fabrication methods |
| CN113977829A (en) * | 2021-09-08 | 2022-01-28 | 北京宝理泰科技有限公司 | Preparation method of hollow microneedle array biosensor |
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