CN104056346B - Isoplanar microneedle array and manufacturing method thereof - Google Patents
Isoplanar microneedle array and manufacturing method thereof Download PDFInfo
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- CN104056346B CN104056346B CN201410266984.8A CN201410266984A CN104056346B CN 104056346 B CN104056346 B CN 104056346B CN 201410266984 A CN201410266984 A CN 201410266984A CN 104056346 B CN104056346 B CN 104056346B
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
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- 230000009286 beneficial effect Effects 0.000 abstract description 2
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- 239000011521 glass Substances 0.000 description 13
- 238000004987 plasma desorption mass spectroscopy Methods 0.000 description 13
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 13
- CXQXSVUQTKDNFP-UHFFFAOYSA-N octamethyltrisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)O[Si](C)(C)C CXQXSVUQTKDNFP-UHFFFAOYSA-N 0.000 description 11
- 229920001486 SU-8 photoresist Polymers 0.000 description 10
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- 239000000243 solution Substances 0.000 description 9
- 229910052751 metal Inorganic materials 0.000 description 8
- 239000002184 metal Substances 0.000 description 8
- 229920005479 Lucite® Polymers 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000012545 processing Methods 0.000 description 6
- 239000003814 drug Substances 0.000 description 5
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- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 230000003796 beauty Effects 0.000 description 2
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- 240000007594 Oryza sativa Species 0.000 description 1
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- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- 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
- A61M2037/0046—Solid microneedles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
- A61M2037/0053—Methods for producing microneedles
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- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Anesthesiology (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Dermatology (AREA)
- Medical Informatics (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Media Introduction/Drainage Providing Device (AREA)
- Microelectronics & Electronic Packaging (AREA)
- Manufacturing & Machinery (AREA)
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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 medicine injection micropin technical field, particularly a kind of different plane micropin battle array
Row and preparation method thereof.
Background technology
Microneedle cutaneous is a kind of emerging medicine-feeding technology, is produced in keratodermatitis and epidermal area by pressing micropin
A large amount of micron-sized ducts, medicine are penetrated to the skin by these ducts in a large amount of blood vessels in skin corium, so as to realize transdermal
Administration.Micropin be capable of achieving over the course for the treatment of it is integrated, portable, painless and accurate, the features such as be efficiently administered, control in diabetes
The aspects such as treatment, chemotherapy, vaccination have unrivaled advantage.Further, since micropin needle point is sharp, size is little, give
Pain and bleeding will not be produced during medicine, the minimally invasive aperture of row can heal quickly, be very suitable for for beauty treatment fields.
Conventional machining methods are difficult to the micropin for making micro-meter scale, and current microneedle configuration is mostly based on microelectron-mechanical
Technique (MEMS) makes., used as a kind of device for penetrating percutaneous drug delivery, its needle point is less, density is higher, concordance for micropin
More strong better, its manufacturing process is simpler, yield rate is higher, cost is more low better.Microneedle array is a kind of typical advanced wide
The three dimensional structure of ratio, MEMS technology are developed from the IC techniques of plane, and the microneedle array for making high-aspect-ratio still has
Certain difficulty.
According to the difference of structure, micropin is divided into coplanar micropin and different plane micropin.The diameter parallel of coplanar micropin in
Base plane, the axis of different plane micropin is perpendicular to base plane.The advantage of coplanar micropin is that processing technology is simple, aciculiform,
With precise control, needle point, pin length can have the disadvantage that micropin number is less.Different plane micropin is then on the contrary, micropin number is more but high
Degree is restricted, and technics comparing is complicated.Current research emphasis be directly processed using various complex techniques it is different
Plane micropin, but think while obtain excellent aciculiform, needle point, pin length and high density, it is unavoidable using complicated technique and costliness
Equipment, be unfavorable for reduces cost, yield rate also is difficult to ensure.
The content of the invention
The technical problem to be solved is：Existing different plane micropin tip height is restricted, and makes
Complex process.
The technical solution adopted for the present invention to solve the technical problems is：A kind of different plane microneedle array, including it is coplanar
Micropin and substrate, coplanar micropin include the base of and more than one needle point and connection needle point, needle point and base same
In plane, coplanar micropin more than two panels is assembled on substrate.
Further limit, elastic buffer cushion block is set between coplanar micropin.
Further limit, the manufacture method of coplanar micropin is：
1) two-dimentional micropin figure is drawn, mask plate is made；
2) layer of metal chromium is sputtered on the glass substrate；
3) subsequent one layer of positive photo glue of spin coating on crome metal, the mask plate made of step 1 are exposed, subsequently use
Developing liquid developing, drying obtain patterned photoresist mask；
4) and then with corrosion corrosion crome metal, photoresist mask is subsequently removed, crome metal mask plate is obtained；
5) SU-8 photoresists are spun in substrate of glass；
6) coplanar micropin is obtained from substrate of glass back-exposure subsequently with developing liquid developing after drying SU-8 photoresists
Structure；
7) coplanar micropin is peeled off from substrate of glass.
The first string coplanar micropin being assembled on substrate is：
With the groove that cooperation is engaged with base on substrate, the base and elastic buffer cushion block of coplanar micropin is by embedding
The mounting means for entering groove is assembled on substrate.
Further limit, filling adhesive between base and the groove of substrate.
By second scheme that coplanar micropin is assembled on substrate it is：
Substrate is the substrate with fixture, including substrate body and fixture, has at least two positioning convex strips in substrate body,
With the draw-in groove that cooperation is corresponded with positioning convex strip on fixture, fixture is arranged in substrate body, and positioning convex strip is embedded in draw-in groove
It is interior, clamping gap is left between draw-in groove and positioning convex strip, the base of coplanar micropin is placed in clamping gap, in fixture and base
The elastic component that fixture is promoted to the side translation for reducing clamping gap is set between plate body, to clamp the bottom of coplanar micropin
Seat.
Further limit, positioning convex strip is elastic buffer cushion block.
Further limit, coplanar micropin of the coplanar micropin for wedge shape, the coplanar micropin of wedge shape are received to needle point side
Narrow, one of side of described two sides for constituting clamping gap is vertical, and another side is same with wedge shape
The inclined plane that plane micropin agrees with.
By the 3rd scheme that coplanar micropin is assembled on substrate it is：
There is in substrate pouring basin, the base of coplanar micropin is placed in pouring basin, by pad between coplanar micropin
Block is spaced from each other and positions, and the depth of pouring basin is being installed into coplanar micropin more than the height of the base of coplanar micropin
Pouring liquid castable in pouring basin, is integrally formed coplanar micropin and substrate after castable solidification.
Further limit, cushion block is elastic buffer cushion block.
For convenience of the assembling of coplanar micropin, further limit, pouring basin has in the side of substrate to be easy to from substrate
Side is put into the lateral opening of coplanar micropin and cushion block, and lateral opening is blocked by groove link stopper.
Further limit, with the locating dowel extended to lateral opening, the base and cushion block of coplanar micropin in pouring basin
On be set in locating dowel with the location hole coordinated with locating dowel, the base and cushion block of coplanar micropin.
By the 4th scheme that coplanar micropin is assembled on substrate it is：
Substrate is fixed using curable liquid baseplate material and is formed, and coplanar micropin solidifies planting in advance in liquid baseplate material
Enter, coplanar micropin is assembled on substrate thereafter by the mode of solidification.
Further limit, the concrete grammar that coplanar micropin is implanted into before the solidification of liquid baseplate material is：
1) the transhipment template of coplanar micropin is made, there is in transhipment template notch cuttype groove, notch cuttype groove includes using
Base portion water jacket in the inside groove of the body sections for accommodating coplanar micropin and for accommodating coplanar micropin, it is coplanar per piece
Micropin one notch cuttype groove of correspondence；
2) needle point of coplanar micropin downward is upside down in the notch cuttype groove of transhipment template；
3) liquid baseplate material is cast in micropin transhipment template；
4) solidify liquid baseplate material；
5) substrate and coplanar micropin of solidification are peeled off from transhipment template from transhipment template.
Further limit, the concrete grammar that coplanar micropin is implanted into before the solidification of liquid baseplate material is：
1) the transhipment template of coplanar micropin is made, transhipment template adopts elastomeric cushion material, has rank in transhipment template
Ladder type groove, notch cuttype groove include for accommodate coplanar micropin body sections inside groove and for accommodating coplanar micropin
Base portion water jacket, one notch cuttype groove of coplanar micropin correspondence, the rank in the transhipment template of elastomeric cushion material per piece
Ladder type groove is before and after's insertion, makes the syringe needle of micropin expose transhipment template；
2) needle point of coplanar micropin downward is upside down in the notch cuttype groove of transhipment template, the pin of coplanar micropin
The surface of point protrusion transhipment template, or maintain an equal level with the surface of transhipment template, or less than the surface of transhipment template, when coplanar
During the surface of the needle point protrusion transhipment template of micropin, below transhipment template by way of padding cushion block, or by turning in placement
The mode of groove is reserved on the platform of fortune template, the needle point of protrusion transhipment template is stepped down；
3) liquid baseplate material is cast in transhipment template；
4) solidify liquid baseplate material, you can obtain different plane microneedle array.
A kind of manufacture method of different plane microneedle array, by the use of above-mentioned different plane microneedle array as master mold, utilizes
Reverse mould technique prepares reusable female mold, then prepares different plane microneedle array with reverse mould technique again.
The invention has the beneficial effects as follows：The needlepoint form of coplanar micropin is easily controlled, and tips quality is good, same using multi-disc
Plane micropin assembled side-by-side into microneedle array both can guarantee that needle point, aciculiform, pin were long, micropin density requirements can be met again.
Coplanar micropin processing technology used in microneedle array manufacturing process, substrate, template machining, female mold are fallen
The techniques such as mould are all more ripe, and cost is relatively low, easily realize, if for producing in batches, the different plane micropin battle array of assembled side-by-side
Row are only used for the master mold that reverse mould makes female mold, and access times are few, can ensure micropin yield rate, reduce microneedle array and make
Cost.
Description of the drawings
The present invention is further described with reference to the accompanying drawings and examples；
Fig. 1 is the manufacturing process schematic diagram of the coplanar micropin of the present invention；
Fig. 2 is the structural representation of the different plane microneedle array in the solution of the present invention 1；
Fig. 3 is the sectional 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 of the elastic buffer cushion block used 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 the structural representation of the different plane microneedle array of one of which in the solution of the present invention 4；
Fig. 9 is the structural representation of another kind of different plane microneedle array in the solution of the present invention 4；
The structural representation for making the female mold of different plane microneedle array of Figure 10 present invention；
The structural representation that the different plane microneedle array to be formed is prepared by reverse mould of Figure 11 present invention；In figure, 1. with flat
Face micropin, 2. substrate, 3. groove, 4. fixture, 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 molds, 14. mask plates, 15. substrate of glass, 16. crome metals,
17. positive photo glue, 18.SU-8 photoresists, 19. elastic buffer cushion blocks.
Specific embodiment
A kind of different plane microneedle array, including coplanar micropin 1 and substrate 2, coplanar micropin 1 include one and one with
In the same plane, coplanar micropin 1 more than two panels is assembled in substrate for the base of upper needle point and connection needle point, needle point and base
On 2, elastic buffer cushion block 19 is set between coplanar micropin 1.
Elastic buffer cushion block 19 has following effect：First, can isolate and control the distance between coplanar micropin 1；2nd, in note
Play a part of to buffer and adjust during penetrating to be pierced into skin depth, the different pressing dynamics of control can be passed through and adjust elastic buffer
The degree of deformation of cushion block 19, and then the length of micropin needle body protrusion elastic buffer cushion block 19 is controlled, adjustment is pierced into the depth of skin.
The invention is intended to merge the advantage of coplanar micropin and different plane micropin, and conjugated polymer micropin technique low cost
Advantage.
Coplanar micropin 1 can be made using existing processing technology, such as dry etching silicon, plating metal processing technology.
Coplanar micropin 1 can also be made using method below, as shown in Figure 1, there is provided one is made with photoetching process
The embodiment of the coplanar micropin 1 of SU-8 materials：
1) two-dimentional micropin figure is drawn with AUTOCAD, make mask plate 14.Needle body is high 300 μm, wide 200 μm, 500 μ of gap
M, the coplanar micropin 1 of monolithic include 10 needle bodies, the high 2mm of base.
2) prepare a piece of K9 glass wafers as substrate of glass 15, the thick gold of one layer of 300nm is sputtered in substrate of glass 15
Category chromium 16；
3) the BP212-37s positive photos glue 17 of subsequent one layer 2 microns thick of spin coating, the mask plate 14 made of step 1 enter
Row exposure, with 0.5% sodium hydroxide developing liquid developing, 100 DEG C of after bake 5min obtain patterned photoresist mask；
4) and then with CR-14 corrosion corrosions crome metal 16, subsequently photoresist is removed with acetone and obtain chromium mask plate, so as to
The chromium mask plate of photoetching SU-8 is transferred in substrate of glass 15, CR-14 corrosive liquids by 5g ammonium ceric nitrates, 20mL acetic acid and
100mL water is formulated；
5) SU-8 photoresists 18 are spun in substrate of glass 15, thickness is 100 μm；
6) from 15 back-exposure of substrate of glass after 90 DEG C of drying；Developing liquid developing is used after drying, coplanar micropin knot is obtained
Structure；
7) coplanar microneedle configuration is placed in 20% sodium hydroxide solution, by coplanar micropin 1 from substrate of glass
Peel off on 15.
Effect is penetrated to improve needle point, when the SU-8 photoresists 18 of coplanar micropin 1 to SU-8 materials expose, from
The back side canted exposure of substrate of glass 15, inclination angle are 70 °, form inclined needle point, to increase the acutance of needle point.
As shown in Fig. 2 by the first string that coplanar micropin 1 is assembled on a substrate 2 being：
With the groove 3 that cooperation is engaged with base on substrate 2, fill in groove 3 for the viscous of bonding micropin base
Knot agent, the groove 3 on substrate 2 are consistent with the base shape of coplanar micropin 1, and 3 depth of groove is slightly above base.By existing
The coplanar micropin 1 that processing technology makes generally comprises dozens of needle body, and base length may be designed as micro- up to several millimeters, depth
Rice magnitude.Groove 3 on substrate 2 can be with the realization of the MEMS processing technique of traditional machining or lower accuracy, Duo Paitong
Plane micropin 1 is assembled on a substrate 2 by the mounting means that base is vertically embedded into groove 3, obtains different plane microneedle array.
The embodiment of a scheme 1 is provided below：
Groove 3 corresponding with the base shape of micropin is made using being laser-ablated on lucite (PMMA) surface, is made
To connect the substrate 2 of coplanar micropin 1.2 surface of substrate drop on as bonding micropin base binding agent PDMS performed polymers
With the mixing liquid of cross-linking agent and smoothen, standing 5min makes part PDMS bonding agents penetrate into groove 3, then dries the PDMS of remnants
Bonding agent.The base of the coplanar micropins of SU-8 1 of monolithic is gripped with tweezers, groove 3 is respectively put into, and is compressed base portion.Entirely
After coplanar 1 installation of micropin in portion, 100 DEG C of drying 10min solidify PDMS bonding agents, obtain Embedded different plane side by side
Microneedle array.
As shown in Figures 3 and 4, by second scheme that coplanar micropin 1 is assembled on a substrate 2 it is：
Substrate 2 is the substrate 2 with fixture 4, including substrate body and fixture 4, is positioned with least two in substrate body
Raised line 5, with the draw-in groove that cooperation is corresponded with positioning convex strip 5 on fixture 4, fixture 4 is arranged in substrate body, positioning convex strip
5 are embedded in draw-in groove, and clamping gap is left between draw-in groove and positioning convex strip 5, and the base of coplanar micropin 1 is placed on clamping gap
It is interior, the elastic component 6 for promoting fixture 4 to the side translation for reducing clamping gap is set between fixture 4 and substrate body, to clamp
The base of coplanar micropin 1.
When coplanar micropin 1 is narrowed to needle point side for the coplanar micropin 1 of wedge shape, and the coplanar micropin 1 of wedge shape,
The one of side for constituting two sides in clamping gap is vertical, and another side is the coplanar micropin 1 with wedge shape
The inclined plane agreed with.
The embodiment of a scheme 2 is provided below：
Fixture 4 is made with lucite, and fixture 4 and spring are arranged in substrate body, fixture 4 is shifted onto between clamping
The maximum direction of gap, is put into the base of coplanar micropin 1 in clamping gap one by one, unclamps fixture 4, spring automatic impaction micropin
Base, forms different plane microneedle array.
As shown in figure 5, by the 3rd scheme that coplanar micropin 1 is assembled on a substrate 2 being：
There is in substrate 2 pouring basin 7, the base of coplanar micropin 1 is placed in pouring basin 7, is led between coplanar micropin 1
Cross cushion block 8 to be spaced from each other and position, the depth of pouring basin 7 is being installed into coplanar more than the height of the base of coplanar micropin 1
Pouring liquid castable in the pouring basin 7 of micropin 1, is integrally formed coplanar micropin 1 and substrate 2 after castable solidification.For
Facilitate the assembling of coplanar micropin 1, pouring basin 7 has in the side of substrate 2 to be easy to coplanar micropin is put into from the side of substrate 2
1 and the lateral opening of cushion block 8, lateral opening is blocked by groove link stopper 9.With extending to lateral opening in pouring basin 7
Locating dowel 10, with the location hole coordinated with locating dowel 10, the bottom of coplanar micropin 1 on the base and cushion block 8 of coplanar micropin 1
Seat and cushion block 8 are set in locating dowel 10.
As shown in fig. 6, cushion block 8 alternatively protrudes the elastic buffer cushion block 19 of 2 plane of substrate, the material of elastic buffer cushion block 19
Matter is flexible rubber.
The embodiment of a scheme 3 is provided below：
Substrate 2 is made with lucite, substrate 2 is poured with pouring basin 7 corresponding with the base shape of coplanar micropin 1
Note groove 7 has in the side of substrate 2 to be easy to be put into the lateral opening of coplanar micropin 1 and cushion block 8 from the side of substrate 2, and
Locating dowel corresponding with the location hole of base 10 is installed in pouring basin 7.7 depth of pouring basin is slightly above the height of base, to pour into a mould
The liquid pouring material of one layer of fixation.Pad is made with metal or lucite, the base one of gasket shape and coplanar micropin 1
Cause, thickness is consistent with the spacing of coplanar micropin 1 or is determined by micropin density.Coplanar micropin 1 is inserted into into pouring basin 7 side by side
In, separated with pad between coplanar micropin 1 per two panels.Coplanar 1 assembled side-by-side of micropin of multi-disc is into different plane microneedle array.With
Groove link stopper 9 blocks the lateral opening of pouring basin 7, with fixed coplanar micropin 1.It is PDMS in pouring basin 7 to pour into a mould PDMS liquid
The mixed liquor of performed polymer and cross-linking agent, it is concordant with 2 upper surface of substrate to liquid level, 3-5 is then heated in the environment of 50-100 DEG C
Hour, make PDMS liquid curings.Thus multiple coplanar micropins 1 different plane microneedle array has been assembled into into just.
As shown in Fig. 7,8 and 9, by the 4th scheme that coplanar micropin 1 is assembled on a substrate 2 it is：
Substrate 2 is fixed using curable liquid baseplate material and is formed, and coplanar micropin 1 is before the solidification of liquid baseplate material
Implantation, makes coplanar micropin 1 assemble on a substrate 2 thereafter by the mode of solidification.
Coplanar micropin 1 liquid baseplate material solidification before implantation concrete grammar be：
1) the transhipment template 11 of coplanar micropin 1 is made, there is notch cuttype groove 12, notch cuttype groove in transhipment template 11
12 include for accommodate coplanar micropin 1 body sections inside groove and base portion water jacket for accommodating coplanar micropin 1,
One notch cuttype groove 12 of the correspondence of coplanar micropin 1 per piece, notch cuttype groove 12 be enough to accommodate body sections, and can make base
More than half exposes transhipment template 11, and notch cuttype groove 12 is arranged side by side；
2) needle point of coplanar micropin 1 downward is upside down in the notch cuttype groove 12 of transhipment template 11；
3) liquid baseplate material is cast in transhipment template 11, and applying pressure makes liquid baseplate material flow and go deep into
To in the gap between base, liquid baseplate material and the base of coplanar micropin 1 is made to bond completely；
4) solidify liquid baseplate material；
5) substrate 2 and coplanar micropin 1 of solidification are peeled off from transhipment template 11 from transhipment template 11.
The embodiment of a scheme 4 is provided below：
Transhipment template 11 also using the making of laser ablation lucite, the groove depth 0.2 of the inside groove of notch cuttype groove 12～
1.5mm, it is long depending on the pin of micropin.The notch cuttype groove 12 of transhipment template 11 is placed upward, respectively by the SU-8 materials of monolithic
Coplanar micropin 1 it is oppositely positioned in step trough, base exposes 0.5mm.Then it is pre- PDMS to be dripped on 11 surface of transhipment template
The mixing liquid of aggressiveness and cross-linking agent, standing 10min makes its levelling, thickness be about 1mm.Then its entirety is dried at 100 DEG C
10min makes PDMS liquid curings, and the substrate 2 that PDMS is solidified is together with the coplanar micropin 1 being implanted into from transhipment template 11
Peel off, both obtained the different plane microneedle array of implanted.
In scheme 4, transhipment template 11 may also be employed elastomeric cushion material, such as soft rubber.The transhipment of quality of rubber materials
The effect elastic buffer cushion block 19 of template 11 is identical.Notch cuttype groove 12 in the transhipment template 11 of elastomeric cushion material is insertion
, expose can the syringe needle of micropin, and the substrate of the coplanar micropin 1 being implanted into need not be peeled off from transhipment template 11.
The needle point of coplanar micropin 1 can protrude the surface of transhipment template 11, as shown in figure 8, or holding with the surface of transhipment template 11
It is flat, or less than the surface of transhipment template 11, when the surface of the needle point protrusion transhipment template 11 of coplanar micropin 1, transport mould
Below plate 11 by way of padding cushion block, or by way of reserving groove on the platform for placing transhipment template 11, to convex
The needle point for going out to transport template 11 is stepped down.
As shown in FIG. 10 and 11, a kind of manufacture method of different plane microneedle array, Utilization plan 1,2,3 and 4 obtain different flat
Face microneedle array prepares reusable female mold 13 using reverse mould technique as master mold, then uses reverse mould technique again
Prepare different plane microneedle array.
With reverse mould technique formed female mold 13 concrete grammar be：Liquid mold materials are poured into main mould under soft state
The needle body surface of tool, under certain vacuum or pressure environment, makes liquid mold materials infilter the space between needle body, treats liquid mould
Separate with master mold after tool material solidification, obtain female mold 13；
The concrete grammar that different plane microneedle array is prepared with reverse mould technique is：Liquid micropin material is poured in the state of softening
Note to female mold 13, under certain vacuum or pressure environment, make liquid micropin material infilter and fill aciculiform groove, treat that liquid is micro-
Separate with female mold 13 after needle material solidification, obtain different plane microneedle array.
The master mold and female mold 13 can be reused, and advantageously reduce cost.
One embodiment is provided below：
Utilization plan 1,2,3 and 4 obtains different plane microneedle array as master mold, and master mold is put in open containers,
One layer of glycerol thin film is deposited with different plane microneedle array, to aid in follow-up PDMS releasing processes.Cast PDMS performed polymers and friendship
The mixing liquid of connection agent, standing 10min makes its levelling, is heated to 100 DEG C and keeps 10min to solidify which.By the PDMS of solidification
Different plane microneedle array is slowly peeled off, then is reduced useless marginal portion, is formed different plane microneedle array female mold 13.
Lucite (PMMA) is positioned over into 13 upper surface of female mold, evacuation is heated to 160 DEG C, keeps 30min, make to melt
The PMMA liquid of change is smoothly flowed in the micropin groove of female mold 13.Cool to room temperature with the furnace, it is slow to peel off female mold 13, prune
Useless marginal portion, that is, obtain the different plane microneedle arrays of PMMA.
The liquid micropin material that different plane microneedle array is prepared with reverse mould technique can be using containing skin care item or medicament
The mixture of effective ingredient, makes different plane microneedle array both as the needle point for piercing through skin, and as medicine.
Claims (2)
1. a kind of different plane microneedle array, is characterized in that：Including coplanar micropin (1) and substrate (2), described coplanar micropin
(1) including one and the base of more than one needle point and connection needle point, needle point and base are in the same plane, more than two panels same
Plane micropin (1) is assembled on substrate (2),
Described substrate (2) is fixed using curable liquid baseplate material and is formed, and coplanar micropin (1) is in liquid baseplate material
Implantation before solidification, makes coplanar micropin (1) be assembled on substrate (2) thereafter by the mode of solidification,
Described coplanar micropin (1) liquid baseplate material solidification before implantation concrete grammar be：
1) the transhipment template (11) of coplanar micropin (1) is made, there is in transhipment template (11) notch cuttype groove (12), notch cuttype
Groove (12) include for accommodate coplanar micropin (1) body sections inside groove and for accommodating the bottom of coplanar micropin (1)
Seating portion water jacket, one notch cuttype groove (12) of coplanar micropin (1) correspondence per piece；
2) needle point of coplanar micropin (1) downward is upside down in the notch cuttype groove (12) of transhipment template (11)；
3) liquid baseplate material is cast in transhipment template (11)；
4) solidify liquid baseplate material；
5) substrate (2) and coplanar micropin (1) of solidification are peeled off from transhipment template (11) from transhipment template (11),
Or, the concrete grammar that coplanar micropin (1) is implanted into before the solidification of liquid baseplate material is：
1) the transhipment template (11) of coplanar micropin (1) is made, transhipment template (11) adopts elastomeric cushion material, transports template
(11) there is on notch cuttype groove (12), notch cuttype groove (12) is included for accommodating the body sections of coplanar micropin (1)
Inside groove and the base portion water jacket for accommodating coplanar micropin (1), one notch cuttype groove of coplanar micropin (1) correspondence per piece
(12), the notch cuttype groove (12) in the transhipment template (11) of elastomeric cushion material is before and after's insertion, makes the syringe needle of micropin can
Expose transhipment template (11)；
2) needle point of coplanar micropin (1) downward is upside down in the notch cuttype groove (12) of transhipment template (11), it is coplanar
The surface of needle point protrusion transhipment template (11) of micropin (1), or maintain an equal level with the surface of transhipment template (11), or less than transhipment
The surface of template (11), when the surface of needle point protrusion transhipment template (11) of coplanar micropin (1), transports below template (11)
By way of padding cushion block, or by way of reserving groove on the platform for placing transhipment template (11), to protrusion transhipment
The needle point of template (11) is stepped down；
3) liquid baseplate material is cast in transhipment template (11)；
4) solidify liquid baseplate material, you can obtain different plane microneedle array.
2. a kind of manufacture method of different plane microneedle array, is characterized in that：Using the different plane microneedle array described in claim 1
As master mold, reusable female mold (13) is prepared using reverse mould technique, then prepared with reverse mould technique again different flat
Face microneedle array.
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| JP6411395B2 (en) * | 2015-03-10 | 2018-10-24 | 富士フイルム株式会社 | Method for producing transdermal absorption sheet |
| CN106426729A (en) * | 2016-11-09 | 2017-02-22 | 江苏信息职业技术学院 | Semiconductor microneedle assembly based on gene therapy, manufacturing method and manufacturing mold |
| WO2018181700A1 (en) * | 2017-03-31 | 2018-10-04 | 凸版印刷株式会社 | Percutaneous administration device |
| CN109531884A (en) * | 2019-01-11 | 2019-03-29 | 江苏熙美生物科技有限公司 | The forming method of micropin mold and micropin mold |
| WO2020227895A1 (en) * | 2019-05-13 | 2020-11-19 | 大连理工大学 | Planar metal micro-needle array and preparation method therefor |
| CN110153651B (en) * | 2019-05-13 | 2021-05-11 | 大连理工大学 | Large length-diameter ratio planar metal microneedle array, preparation method and clamping and puncturing auxiliary device thereof |
| WO2020227900A1 (en) * | 2019-05-13 | 2020-11-19 | 大连理工大学 | Planar metal microneedle array with large length-diameter ratio, and preparation method, clamping aiding device and insertion aiding device therefor |
| DE102020109157A1 (en) * | 2020-04-02 | 2021-10-07 | Lts Lohmann Therapie-Systeme Ag | Carrier element for microneedles as well as microneedle array device |
| CN112191964B (en) * | 2020-09-07 | 2021-11-19 | 大连理工大学 | Method for preparing three-dimensional metal microneedle array by directly utilizing razor blade |
| CN115227956A (en) * | 2022-07-26 | 2022-10-25 | 空芯微医疗科技(上海)有限责任公司 | Preparation method of hollow microneedle |
| CN115227957A (en) * | 2022-07-26 | 2022-10-25 | 空芯微医疗科技(上海)有限责任公司 | Method for preparing hollow microneedle and product thereof |
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| US6749575B2 (en) * | 2001-08-20 | 2004-06-15 | Alza Corporation | Method for transdermal nucleic acid sampling |
| US20030078549A1 (en) * | 2001-06-08 | 2003-04-24 | Stupar Philip Anthony | Microfabricated surgical devices and methods of making the same |
| WO2005069758A2 (en) * | 2004-01-09 | 2005-08-04 | Alza Corporation | Frequency assisted transdermal agent delivery method and system |
| KR100682534B1 (en) * | 2005-10-10 | 2007-02-15 | 한국과학기술원 | Method for manufacturing microneedle array |
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