CN104056346A - Isoplanar microneedle array and manufacturing method thereof - Google Patents
Isoplanar microneedle array and manufacturing method thereof Download PDFInfo
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- CN104056346A CN104056346A CN201410266984.8A CN201410266984A CN104056346A CN 104056346 A CN104056346 A CN 104056346A CN 201410266984 A CN201410266984 A CN 201410266984A CN 104056346 A CN104056346 A CN 104056346A
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- isoplanar
- micropin
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- different plane
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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
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B81—MICROSTRUCTURAL TECHNOLOGY
- B81B—MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
- B81B7/00—Microstructural systems; Auxiliary parts of microstructural devices or systems
- B81B7/04—Networks or arrays of similar microstructural devices
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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
-
- 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
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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
- A61M2037/0053—Methods for producing microneedles
Abstract
The invention relates to an isoplanar microneedle array and a manufacturing method thereof. The isoplanar microneedle array comprises coplanar microneedles and a base plate, wherein each coplanar microneedle comprises one or more than one needle point and a base which is connected with the needle point, the needle point and the base are in a same plane, and more than two coplanar microneedles are assembled on the base plate. The manufacturing method of the isoplanar microneedle array comprises the steps of utilizing the isoplanar microneedle array as a main die, manufacturing a negative die which can be reused by utilizing a reverse die casting technology, and then manufacturing the isoplanar microneedle array by using the reverse die casting technology again. The isoplanar microneedle array and the manufacturing method which are disclosed by the invention have the beneficial effects that the shape of the needle points of the coplanar microneedles is easily controlled, the quality of the needle points is good, the needle points, the needle shape and the needle length can be ensured by utilizing the microneedle array assembled by multiple coplanar microneedles side by side, and the microneedle density requirement can be met; technologies which are used during a microneedle array manufacturing process are all more mature and are easily realized, the isoplanar microneedle array assembled side by side is just used for the main die which is used for manufacturing the negative die in a reverse die casting way if the technologies are used for batch production, the use times are few, the finished product rate of the coplanar microneedles can be ensured, and the manufacturing cost of the microneedle array is reduced.
Description
Technical field
The present invention relates to medical beauty treatment instrument and medical injection micropin technical field, particularly a kind of different plane microneedle array and preparation method thereof.
Background technology
Microneedle cutaneous is a kind of emerging medicine-feeding technology, by pressing micropin, at keratodermatitis and epidermal area, produces a large amount of micron-sized ducts, in a large amount of blood vessels that medicine penetrates to the skin in skin corium by these ducts, thereby realizes transdermal administration.The features such as that micropin can be realized in therapeutic process is integrated, portable, painless and accurate, efficient administration, have unrivaled advantage at aspects such as treating diabetes, chemotherapy, vaccinations.In addition, because micropin needle point is sharp, size is little, during administration, can not produce pain and bleeding, Wicresoft's aperture of row can heal very soon, is extremely suitable for beauty treatment fields.
Traditional mechanical processing method is difficult to make the micropin of micro-meter scale, and current microneedle configuration is made based on microelectron-mechanical technique (MEMS) mostly.Micropin is as a kind of device for transdermal administration, and its needle point is less, density is higher, concordance is better more by force, and its manufacturing process is simpler, yield rate is higher, cost is more low better.Microneedle array is a kind of three dimensional structure of typical high-aspect-ratio, and MEMS technique is to develop from the IC technique of plane, for making the microneedle array of high-aspect-ratio, still has certain difficulty.
According to the difference of structure, micropin is divided into isoplanar micropin and different plane micropin.The axis of isoplanar micropin is parallel to base plane, and the axis of different plane micropin is perpendicular to base plane.The advantage of isoplanar micropin is that processing technology is simple, and aciculiform, needle point, pin length can accurately be controlled, and shortcoming is that micropin number is less.Different plane micropin is on the contrary, and micropin number is many, but is highly restricted, and technique more complicated.Current research emphasis is to utilize various comparatively complicated technologies directly to process different plane micropin, but think to obtain good aciculiform, needle point, pin length and high density simultaneously, unavoidable complicated technique and the expensive equipment of using, is unfavorable for reducing costs, and yield rate is also difficult to guarantee.
Summary of the invention
Technical problem to be solved by this invention is: existing different plane micropin needle point height is restricted, and complex manufacturing technology.
The technical solution adopted for the present invention to solve the technical problems is: a kind of different plane microneedle array, comprise isoplanar micropin and substrate, isoplanar micropin comprises more than one and one needle point and the base that is connected needle point, needle point and base are in same plane, and two above isoplanar micropins are assembled on substrate.
Further limit, elastic buffer cushion block is set between the micropin of isoplanar.
Further limit, the manufacture method of isoplanar micropin is:
1) draw two-dimentional micropin figure, make mask plate;
2) sputter layer of metal chromium in substrate of glass;
3) spin coating one deck eurymeric photoresist on crome metal subsequently, exposes with the mask plate that step 1 is made, and uses subsequently developing liquid developing, dries and obtains patterned photoresist mask;
4) then use corrosive liquid corroding metal chromium, remove subsequently photoresist mask, obtain crome metal mask plate;
5) SU-8 photoresist is spun in substrate of glass;
6) dry after SU-8 photoresist from substrate of glass back-exposure, use subsequently developing liquid developing, obtain isoplanar microneedle configuration;
7) isoplanar micropin is peeled off from substrate of glass.
The first string that isoplanar micropin is assembled on substrate is:
On substrate, have the groove that matches with base and coordinate, the base of isoplanar micropin and elastic buffer cushion block are assembled on substrate by embedding the mounting means of groove.
Further limit filling adhesive between base and the groove of substrate.
Second scheme that isoplanar micropin is assembled on substrate is:
Substrate is the substrate with jig, comprise substrate body and jig, in substrate body, there are at least two positioning convex strips, on jig, have and the positioning convex strip draw-in groove of corresponding matching one by one, jig is arranged in substrate body, positioning convex strip is embedded in draw-in groove, between draw-in groove and positioning convex strip, leave clamping gap, the base of isoplanar micropin is placed in clamping gap, between jig and substrate body, arrange and promote jig to the elastic component that dwindles a side translation in clamping gap, to clamp the base of isoplanar micropin.
Further limit, positioning convex strip is elastic buffer cushion block.
Further limit, isoplanar micropin is the isoplanar micropin of wedge shape, the isoplanar micropin of wedge shape narrows to needle point one side, and one of them side of two sides in described formation clamping gap is vertical, the inclined plane that agree with for the isoplanar micropin with wedge shape another side.
The 3rd scheme that isoplanar micropin is assembled on substrate is:
In substrate, there is pouring basin, the base of isoplanar micropin is placed in pouring basin, between the micropin of isoplanar, by cushion block, be spaced from each other and locate, the degree of depth of pouring basin is greater than the height of the base of isoplanar micropin, pouring liquid castable in the pouring basin that is fit into isoplanar micropin becomes one isoplanar micropin and substrate after castable is solidified.
Further limit, cushion block is elastic buffer cushion block.
For convenience of the assembling of isoplanar micropin, further limit, pouring basin has the lateral opening of being convenient to put into from the side of substrate isoplanar micropin and cushion block in the side of substrate, and lateral opening carries out shutoff by groove link stopper.
Further limit, have the locating dowel of extending to lateral opening in pouring basin, have the locating hole coordinating with locating dowel on the base of isoplanar micropin and cushion block, base and the cushion block of isoplanar micropin are set in locating dowel.
The 4th scheme that isoplanar micropin is assembled on substrate is:
Substrate adopts curable liquid baseplate material fixedly to form, and isoplanar micropin is implanted before liquid baseplate material solidifies, and by curing mode, isoplanar micropin is assembled on substrate thereafter.
Further limit, the concrete grammar that isoplanar micropin is implanted before liquid baseplate material solidifies is:
1) make the transhipment template of isoplanar micropin, in transhipment template, there is notch cuttype groove, notch cuttype groove comprise for hold isoplanar micropin needle body part inside groove and for holding the base portion water jacket of isoplanar micropin, the every corresponding notch cuttype groove of isoplanar micropin;
2) by downward being upside down in the notch cuttype groove of transporting template of the needle point of isoplanar micropin;
3) liquid baseplate material is cast in micropin transhipment template;
4) solidify liquid baseplate material;
5) transhipment template, by solidifying the substrate and the isoplanar micropin that form, from transhipment template, peel off.
Further limit, the concrete grammar that isoplanar micropin is implanted before liquid baseplate material solidifies is:
1) make the transhipment template of isoplanar micropin, transhipment template adopts elastomeric cushion material, in transhipment template, there is notch cuttype groove, notch cuttype groove comprise for hold isoplanar micropin needle body part inside groove and for holding the base portion water jacket of isoplanar micropin, the every corresponding notch cuttype groove of isoplanar micropin, notch cuttype groove in the transhipment template of elastomeric cushion material connects before and after being, makes the syringe needle of micropin can expose transhipment template;
2) by downward being upside down in the notch cuttype groove of transporting template of the needle point of isoplanar micropin, the needle point of isoplanar micropin protrudes the surface of transhipment template, or maintain an equal level with the surface of transhipment template, or the surface lower than transhipment template, when the needle point of isoplanar micropin protrudes transhipment template surperficial, the mode of pad cushion block is passed through in transhipment template below, or by reserving the mode of groove on the platform placing transhipment template, to protruding the needle point of transhipment template, steps down;
3) liquid baseplate material is cast in transhipment template;
4) solidify liquid baseplate material, can obtain different plane microneedle array.
A manufacture method for different plane microneedle array, utilizes above-mentioned different plane microneedle array as main mould, utilizes reverse mould technique to prepare reusable female mold, and then prepares different plane microneedle array by reverse mould technique.
The invention has the beneficial effects as follows: the needlepoint form of isoplanar micropin is easily controlled, tips quality is good, and the microneedle array that utilizes multi-disc isoplanar micropin to be assembled into side by side can guarantee that needle point, aciculiform, pin are long, can meet micropin density requirements again.
The techniques such as the isoplanar micropin processing technology of using in microneedle array manufacturing process, substrate, template machining, female mold reverse mould are all comparatively ripe, cost is lower, easily realize, if for batch production, the different plane microneedle array of assembling is only made the main mould of female mold for reverse mould side by side, access times are few, can ensure micropin yield rate, reduce microneedle array cost of manufacture.
Accompanying drawing explanation
Below in conjunction with drawings and Examples, the present invention is further described;
Fig. 1 is the manufacturing process schematic diagram of isoplanar of the present invention micropin;
Fig. 2 is the structural representation of the different plane microneedle array in the solution of the present invention 1;
Fig. 3 is the cutaway view of the different plane microneedle array in the solution of the present invention 2;
Fig. 4 is the axonometric chart of the different plane microneedle array in the solution of the present invention 2;
Fig. 5 is the manufacturing process schematic diagram of the different plane microneedle array of the solution of the present invention 3;
Fig. 6 is the manufacture process schematic diagram that uses elastic buffer cushion block in scheme 3 of the present invention;
Fig. 7 is the structural representation of the transhipment template in the solution of the present invention 4;
Fig. 8 is a kind of structural representation of different plane microneedle array wherein in the solution of the present invention 4;
Fig. 9 is the structural representation of the different plane microneedle array of the another kind in the solution of the present invention 4;
Figure 10 is of the present invention for making the structural representation of the female mold of different plane microneedle array;
Figure 11 structural representation of preparing the different plane microneedle array forming by reverse mould of the present invention; In figure, 1. isoplanar micropin, 2. substrate, 3. groove, 4. jig, 5. positioning convex strip, 6. elastic component, 7. pouring basin, 8. cushion block, 9. groove link stopper, 10. locating dowel, 11. transhipment templates, 12. notch cuttype grooves, 13. female mold, 14. mask plates, 15. substrate of glass, 16. crome metals, 17. eurymeric photoresists, 18.SU-8 photoresist, 19. elastic buffer cushion blocks.
The specific embodiment
A kind of different plane microneedle array, comprise isoplanar micropin 1 and substrate 2, isoplanar micropin 1 comprises more than one and one needle point and the base that is connected needle point, needle point and base are in same plane, two above isoplanar micropins 1 are assembled on substrate 2, and elastic buffer cushion block 19 is set between isoplanar micropin 1.
Elastic buffer cushion block 19 has following effect: the distance between, can isolated controlling isoplanar micropin 1; Two, in injection process, play buffering and adjust the effect of thrusting skin depth, can adjust by controlling the different dynamics of pressing the degree of deformation of elastic buffer cushion block 19, and then control the length that micropin needle body protrudes elastic buffer cushion block 19, adjust the degree of depth of thrusting skin.
The invention is intended to merge the advantage of isoplanar micropin and different plane micropin, and conjugated polymer micropin technique advantage cheaply.
Isoplanar micropin 1 can utilize existing processing technology to make, as dry etching silicon, plated metal processing technology.
Isoplanar micropin 1 can also profit be made in the following method, as shown in Figure 1, provides an embodiment who makes the isoplanar micropin 1 of SU-8 material with photoetching process:
1) with AUTOCAD, draw two-dimentional micropin figure, make mask plate 14.The high 300 μ m of needle body, wide 200 μ m, gap 500 μ m, monolithic isoplanar micropin 1 comprises 10 needle bodies, the high 2mm of base.
2) prepare a slice K9 glass wafer as substrate of glass 15, the thick crome metal 16 of sputter one deck 300nm in substrate of glass 15;
3) the BP212-37s eurymeric photoresist 17 of spin coating one deck 2 micron thickness subsequently, exposes with the mask plate 14 that step 1 is made, the sodium hydroxide developing liquid developing with 0.5%, and 100 ℃ of after bake 5min obtain patterned photoresist mask;
4) then use CR-14 corrosive liquid corroding metal chromium 16, with acetone, remove photoresist subsequently and obtain chromium mask plate, thereby the chromium mask plate that photoetching SU-8 is used is transferred in substrate of glass 15, CR-14 corrosive liquid is formulated by 5g ammonium ceric nitrate, 20mL acetic acid and 100mL water;
5) SU-8 photoresist 18 is spun in substrate of glass 15, thickness is 100 μ m;
6) after 90 ℃ of oven dry from substrate of glass 15 back-exposures; After drying, with developing liquid developing, obtain isoplanar microneedle configuration;
7) isoplanar microneedle configuration is placed in 20% sodium hydroxide solution, isoplanar micropin 1 is peeled off from substrate of glass 15.
For improving the effect that penetrates of needle point, when SU-8 photoresist 18 exposure of the isoplanar micropin 1 to SU-8 material, from the back side canted exposure of substrate of glass 15, inclination angle is 70 °, forms the needle point of inclination, to increase the acutance of needle point.
As shown in Figure 2, the first string isoplanar micropin 1 being assembled on substrate 2 is:
On substrate 2, have the groove 3 that matches with base and coordinate, fill the binding agent for bonding micropin base in groove 3, the groove 3 on substrate 2 is consistent with the base shape of isoplanar micropin 1, and groove 3 degree of depth are a little more than base.The isoplanar micropin 1 of making by existing processing technology generally comprises dozens of needle body, and base length can reach several millimeters, and the degree of depth can be designed to micron dimension.Groove 3 on substrate 2 can be realized by the MEMS processing technique of traditional machining or lower accuracy, arranges the mounting means that isoplanar micropin 1 vertically embeds groove 3 by base more and is assembled on substrate 2, obtains different plane microneedle array.
The embodiment of a scheme 1 is provided below:
Utilization is laser-ablated in the making groove 3 corresponding with the base shape of micropin on lucite (PMMA) surface, as the substrate 2 that connects isoplanar micropin 1.On substrate 2 surface, drip as the PDMS performed polymer of binding agent and the mixing material of cross-linking agent of bonding micropin base and smoothen, standing 5min makes part PDMS bonding agent infiltrate groove 3, then dries remaining PDMS bonding agent.With the base of the SU-8 isoplanar micropin 1 of tweezers gripping monolithic, put into respectively groove 3, and compress base portion.All, after micropin 1 installation of isoplanar, dry 10min for 100 ℃ PDMS bonding agent is solidified, obtain Embedded different plane microneedle array side by side.
As shown in Figures 3 and 4, second scheme isoplanar micropin 1 being assembled on substrate 2 is:
Substrate 2 is the substrate 2 with jig 4, comprise substrate body and jig 4, in substrate body, there are at least two positioning convex strips 5, on jig 4, have and positioning convex strip 5 draw-in groove of corresponding matching one by one, jig 4 is arranged in substrate body, positioning convex strip 5 is embedded in draw-in groove, between draw-in groove and positioning convex strip 5, leave clamping gap, the base of isoplanar micropin 1 is placed in clamping gap, between jig 4 and substrate body, arrange and promote jig 4 to the elastic component 6 that dwindles a side translation in clamping gap, to clamp the base of isoplanar micropin 1.
When the isoplanar micropin 1 isoplanar micropin 1 that is wedge shape, and the isoplanar micropin 1 of wedge shape narrows to needle point one side, and one of them side that forms two sides in clamping gap is vertical, the inclined plane that agree with for the isoplanar micropin 1 with wedge shape another side.
The embodiment of a scheme 2 is provided below:
With lucite, make jig 4, and by jig 4 and spring fitting in substrate body, jig 4 is shifted onto to the direction of clamping gap maximum, the base of isoplanar micropin 1 is put into clamping gap one by one, unclamp jig 4, spring automatic impaction micropin base, forms different plane microneedle array.
As shown in Figure 5, the 3rd scheme isoplanar micropin 1 being assembled on substrate 2 is:
In substrate 2, there is pouring basin 7, the base of isoplanar micropin 1 is placed in pouring basin 7, between isoplanar micropin 1, by cushion block 8, be spaced from each other and locate, the degree of depth of pouring basin 7 is greater than the height of the base of isoplanar micropin 1, in the interior pouring liquid castable of the pouring basin 7 that is fit into isoplanar micropin 1, after castable is solidified, isoplanar micropin 1 and substrate 2 are become one.For convenience of the assembling of isoplanar micropin 1, pouring basin 7 has the lateral opening of being convenient to put into from the side of substrate 2 isoplanar micropin 1 and cushion block 8 in the side of substrate 2, and lateral opening carries out shutoff by groove link stopper 9.In pouring basin 7, have the locating dowel 10 of extending to lateral opening, on the base of isoplanar micropin 1 and cushion block 8, have the locating hole coordinating with locating dowel 10, the base of isoplanar micropin 1 and cushion block 8 are set in locating dowel 10.
As shown in Figure 6, cushion block 8 also can be the elastic buffer cushion block 19 that protrudes substrate 2 planes, and the material of elastic buffer cushion block 19 is flexible rubber.
The embodiment of a scheme 3 is provided below:
With lucite, make substrate 2, substrate 2 has the pouring basin corresponding with the base shape of isoplanar micropin 17, pouring basin 7 has the lateral opening of being convenient to put into from the side of substrate 2 isoplanar micropin 1 and cushion block 8 in the side of substrate 2, and in the interior installation of pouring basin 7 locating dowel 10 corresponding with the locating hole of base.Pouring basin 7 degree of depth are a little more than the height of base, to pour into a mould the fixedly liquid pouring material of use of one deck.With metal or lucite, make pad, gasket shape is consistent with the base of isoplanar micropin 1, and the spacing of thickness and isoplanar micropin 1 is consistent or determined by micropin density.Isoplanar micropin 1 is inserted in pouring basin 7 side by side, between every two isoplanar micropins 1, with pad, separates.Multi-disc isoplanar micropin 1 is assembled into different plane microneedle array side by side.With the lateral opening of groove link stopper 9 shutoff pouring basins 7, with fixing isoplanar micropin 1.At the interior cast of pouring basin 7 PDMS liquid, be the mixed liquor of PDMS performed polymer and cross-linking agent, concordant with substrate 2 upper surfaces to liquid level, then under the environment of 50-100 ℃, heat 3-5 hour, make PDMS liquid curing.Just a plurality of isoplanars micropin 1 has been assembled into different plane microneedle array thus.
As Fig. 7, shown in 8 and 9, the 4th scheme that isoplanar micropin 1 is assembled on substrate 2 is:
Substrate 2 adopts curable liquid baseplate material fixedly to form, and isoplanar micropin 1 is implanted before liquid baseplate material solidifies, and by curing mode, isoplanar micropin 1 is assembled on substrate 2 thereafter.
The concrete grammar that isoplanar micropin 1 is implanted before liquid baseplate material solidifies is:
1) make the transhipment template 11 of isoplanar micropin 1, in transhipment template 11, there is notch cuttype groove 12, notch cuttype groove 12 comprise for hold isoplanar micropin 1 needle body part inside groove and for holding the base portion water jacket of isoplanar micropin 1, the every corresponding notch cuttype groove 12 of isoplanar micropin 1, notch cuttype groove 12 is enough to hold needle body part, and can make over half the exposing of base transport template 11, notch cuttype groove 12 is arranged side by side;
2) by downward being upside down in the notch cuttype groove 12 of transporting template 11 of the needle point of isoplanar micropin 1;
3) liquid baseplate material is cast in transhipment template 11, and exerts pressure and liquid baseplate material is flowed and be deep in the gap between base, make the base of liquid baseplate material and isoplanar micropin 1 completely bonding;
4) solidify liquid baseplate material;
5) transhipment template 11, by solidifying the substrate 2 and the isoplanar micropin 1 that form, from transhipment template 11, peel off.
The embodiment of a scheme 4 is provided below:
Transhipment template 11 also adopts laser ablation lucite to make, and the groove depth 0.2～1.5mm of the inside groove of notch cuttype groove 12, depends on that the pin of micropin is long.The notch cuttype groove 12 of transhipment template 11 is placed upward, respectively the isoplanar micropin 1 of the SU-8 material of monolithic is oppositely placed in step trough, and base exposes 0.5mm.Then on transhipment template 11 surfaces, drip the mixing material of PDMS performed polymer and cross-linking agent, standing 10min makes its levelling, and thickness is about 1mm.Then its integral body is dried to 10min at 100 ℃ and make PDMS liquid curing, PDMS is solidified to the substrate 2 forming and peel off from transhipment template 11 together with the isoplanar micropin 1 of implanting, both obtained the different plane microneedle array of implanted.
In scheme 4, transhipment template 11 also can adopt elastomeric cushion material, as soft rubber.The effect elastic buffer cushion block 19 of the transhipment template 11 of quality of rubber materials is identical.Notch cuttype groove 12 in the transhipment template 11 of elastomeric cushion material connects, and can make the syringe needle of micropin expose, and the substrate of the isoplanar micropin 1 of implanting need to not peeled off from transhipment template 11.The needle point of isoplanar micropin 1 can protrude the surface of transhipment template 11, as shown in Figure 8, or maintain an equal level with the surface of transhipment template 11, or the surface lower than transhipment template 11, when the needle point of isoplanar micropin 1 protrudes transhipment template 11 surperficial, the mode of pad cushion block is passed through in transhipment template 11 belows, or by reserving the mode of groove on the platform placing transhipment template 11, to protruding the needle point of transhipment template 11, steps down.
As shown in FIG. 10 and 11, a kind of manufacture method of different plane microneedle array, utilize scheme 1,2,3 and 4 to obtain different plane microneedle array as main mould, utilize reverse mould technique to prepare reusable female mold 13, and then prepare different plane microneedle array by reverse mould technique.
The concrete grammar that forms female mold 13 by reverse mould technique is: liquid mold materials is poured into the needle body surface of main mould under soft state, under certain vacuum or pressure environment, make liquid mold materials infilter the space between needle body, separated with main mould after liquid mold materials solidifies, obtain female mold 13;
The concrete grammar of preparing different plane microneedle array by reverse mould technique is: liquid micropin material is poured into female mold 13 under softening state, under certain vacuum or pressure environment, make liquid micropin material infilter and fill aciculiform groove, separated with female mold 13 after liquid micropin material cured, obtain different plane microneedle array.
This main mould and female mold 13 can be reused, and are conducive to reduce costs.
An embodiment is provided below:
Utilize scheme 1,2,3 and 4 to obtain different plane microneedle array as main mould, main mould is put into open containers, and evaporation one deck glycerol thin film on different plane microneedle array, with the PDMS releasing process of aid in later.The mixing material of cast PDMS performed polymer and cross-linking agent, standing 10min makes its levelling, is heated to 100 ℃ and keep 10min that it is solidified.Curing PDMS is slowly peeled off to different plane microneedle array, then reduce useless marginal portion, form different female mold 13 for plane microneedle array.
Lucite (PMMA) is positioned over to female mold 13 upper surfaces, and evacuation is heated to 160 ℃, keeps 30min, and the PMMA liquid melting is flowed in the micropin groove of female mold 13 smoothly.Cool to room temperature with the furnace, slowly peel off female mold 13, prune useless marginal portion, obtain the different plane microneedle array of PMMA.
With reverse mould technique prepare different plane microneedle array liquid micropin material can adopt the mixture that contains skin care item or medicament effective ingredient, make different plane microneedle array both as piercing through the needle point of skin, again as medicine.
Claims (16)
1. a different plane microneedle array, it is characterized in that: comprise isoplanar micropin (1) and substrate (2), described isoplanar micropin (1) comprises more than one and one needle point and the base that is connected needle point, needle point and base are in same plane, and two above isoplanar micropins (1) are assembled on substrate (2).
2. different plane microneedle array according to claim 1, is characterized in that: elastic buffer cushion block (19) is set between isoplanar micropin (1).
3. different plane microneedle array according to claim 1, is characterized in that: the manufacture method of described isoplanar micropin (1) is:
1) draw two-dimentional micropin figure, make mask plate (14);
2) at the upper sputter layer of metal chromium (16) of substrate of glass (15);
3) subsequently at the upper spin coating one deck eurymeric photoresist (17) of crome metal (16), with the mask plate (14) that step 1 is made, expose, use subsequently developing liquid developing, dry and obtain patterned photoresist mask;
4) then use corrosive liquid corroding metal chromium (16), remove subsequently photoresist mask, obtain crome metal mask plate;
5) SU-8 photoresist (18) is spun in substrate of glass (15);
6) dry after SU-8 photoresist (18) from substrate of glass (15) back-exposure, use subsequently developing liquid developing, obtain isoplanar microneedle configuration;
7) isoplanar micropin (1) is peeled off from substrate of glass (15).
4. different plane microneedle array according to claim 2, it is characterized in that: on described substrate (2), have the groove (3) that matches with base and coordinate, the base of isoplanar micropin (1) and elastic buffer cushion block (19) are assembled on substrate (2) by embedding the mounting means of groove (3).
5. different plane microneedle array according to claim 4, is characterized in that: filling adhesive between the groove (3) of described base and substrate (2).
6. different plane microneedle array according to claim 1, it is characterized in that: described substrate (2) is the substrate (2) of band jig (4), comprise substrate body and jig (4), in substrate body, there are at least two positioning convex strips (5), on jig (4), have and positioning convex strip (5) draw-in groove of corresponding matching one by one, jig (4) is arranged in substrate body, positioning convex strip (5) is embedded in draw-in groove, draw-in groove and positioning convex strip leave clamping gap between (5), the base of isoplanar micropin (1) is placed in clamping gap, between jig (4) and substrate body, arrange and promote jig (4) to the elastic component (6) that dwindles a side translation in clamping gap, to clamp the base of isoplanar micropin (1).
7. different plane microneedle array according to claim 6, is characterized in that: described positioning convex strip (5) is elastic buffer cushion block (19).
8. according to the different plane microneedle array described in claim 6 or 7, it is characterized in that: described isoplanar micropin (1) is the isoplanar micropin (1) of wedge shape, the isoplanar micropin (1) of wedge shape narrows to needle point one side, one of them side of two sides in described formation clamping gap is vertical, the inclined plane that agree with for the isoplanar micropin (1) with wedge shape another side.
9. different plane microneedle array according to claim 1, it is characterized in that: in described substrate (2), there is pouring basin (7), the base of isoplanar micropin (1) is placed in pouring basin (7), between isoplanar micropin (1), by cushion block (8), be spaced from each other and locate, the degree of depth of pouring basin (7) is greater than the height of the base of isoplanar micropin (1), pouring liquid castable in being fit into the pouring basin (7) of isoplanar micropin (1) becomes one isoplanar micropin (1) and substrate (2) after castable is solidified.
10. different plane microneedle array according to claim 9, is characterized in that: described cushion block is elastic buffer cushion block (19).
11. according to the different plane microneedle array described in claim 9 or 10, it is characterized in that: described pouring basin (7) has the lateral opening of being convenient to put into from the side of substrate (2) isoplanar micropin (1) and cushion block (8) in the side of substrate (2), lateral opening carries out shutoff by groove link stopper (9).
12. according to the different plane microneedle array described in claim 9 or 10, it is characterized in that: the locating dowel (10) of extending to lateral opening in described pouring basin (7), on the base of isoplanar micropin (1) and cushion block (8), have the locating hole coordinating with locating dowel (10), the base of isoplanar micropin (1) and cushion block (8) are set in locating dowel (10).
13. different plane microneedle arrays according to claim 1, it is characterized in that: described substrate (2) adopts curable liquid baseplate material fixedly to form, isoplanar micropin (1) is implanted before liquid baseplate material solidifies, and by curing mode, isoplanar micropin (1) is assembled on substrate (2) thereafter.
14. different plane microneedle arrays according to claim 13, is characterized in that: the concrete grammar that described isoplanar micropin (1) is implanted before liquid baseplate material solidifies is:
1) make the transhipment template (11) of isoplanar micropin (1), in transhipment template (11), there is notch cuttype groove (12), notch cuttype groove (12) comprise for hold isoplanar micropin (1) needle body part inside groove and for holding the base portion water jacket of isoplanar micropin (1), the corresponding notch cuttype groove (12) of every isoplanar micropin (1);
2) by downward being upside down in the notch cuttype groove (12) of transporting template (11) of the needle point of isoplanar micropin (1);
3) liquid baseplate material is cast in transhipment template (11);
4) solidify liquid baseplate material;
5) transhipment template (11), by solidifying the substrate (2) and the isoplanar micropin (1) that form, from transhipment template (11), peel off.
15. different plane microneedle arrays according to claim 13, is characterized in that: the concrete grammar that described isoplanar micropin (1) is implanted before liquid baseplate material solidifies is:
1) make the transhipment template (11) of isoplanar micropin (1), transhipment template (11) adopts elastomeric cushion material, in transhipment template (11), there is notch cuttype groove (12), notch cuttype groove (12) comprise for hold isoplanar micropin (1) needle body part inside groove and for holding the base portion water jacket of isoplanar micropin (1), the corresponding notch cuttype groove (12) of every isoplanar micropin (1), notch cuttype groove (12) in the transhipment template (11) of elastomeric cushion material connects before and after being, makes the syringe needle of micropin can expose transhipment template (11);
2) by downward being upside down in the notch cuttype groove (12) of transporting template (11) of the needle point of isoplanar micropin (1), the needle point of isoplanar micropin (1) protrudes the surface of transhipment template (11), or maintain an equal level with the surface of transhipment template (11), or the surface lower than transhipment template (11), when the needle point of isoplanar micropin (1) protrudes transhipment template (11) surperficial, transhipment template (11) below is by the mode of pad cushion block, or by the mode of reserved groove on the platform placing transhipment template (11), to protruding the needle point of transhipment template (11), step down;
3) liquid baseplate material is cast in transhipment template (11);
4) solidify liquid baseplate material, can obtain different plane microneedle array.
The manufacture method of 16. 1 kinds of different plane microneedle arrays, it is characterized in that: utilize different plane microneedle array described in claim 1,3,6,9,13 or 14 as main mould, utilize reverse mould technique to prepare reusable female mold (13), and then prepare different plane microneedle array by reverse mould technique.
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| CN106512199A (en) | 2017-03-22 |
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