CN1321706C - An array type microneedle soft substrate structure and its manufacturing method - Google Patents
An array type microneedle soft substrate structure and its manufacturing method Download PDFInfo
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- CN1321706C CN1321706C CNB031370276A CN03137027A CN1321706C CN 1321706 C CN1321706 C CN 1321706C CN B031370276 A CNB031370276 A CN B031370276A CN 03137027 A CN03137027 A CN 03137027A CN 1321706 C CN1321706 C CN 1321706C
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- needle
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- spicule
- soft substrate
- sidewall
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- 239000000758 substrate Substances 0.000 title claims abstract description 45
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 22
- 239000000463 material Substances 0.000 claims abstract description 66
- 238000000034 method Methods 0.000 claims abstract description 21
- 229920002120 photoresistant polymer Polymers 0.000 claims description 17
- 239000011248 coating agent Substances 0.000 claims description 9
- 238000000576 coating method Methods 0.000 claims description 9
- -1 polydimethylsiloxane Polymers 0.000 claims description 9
- 238000005530 etching Methods 0.000 claims description 8
- 239000004698 Polyethylene Substances 0.000 claims description 4
- 239000004743 Polypropylene Substances 0.000 claims description 4
- 239000004205 dimethyl polysiloxane Substances 0.000 claims description 4
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 claims description 4
- 229920000573 polyethylene Polymers 0.000 claims description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 3
- 229920001155 polypropylene Polymers 0.000 claims description 3
- 239000000741 silica gel Substances 0.000 claims description 3
- 229910002027 silica gel Inorganic materials 0.000 claims description 3
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims 2
- 239000003292 glue Substances 0.000 claims 2
- 238000007740 vapor deposition Methods 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 14
- 238000005516 engineering process Methods 0.000 description 13
- 239000000126 substance Substances 0.000 description 8
- 229940079593 drug Drugs 0.000 description 6
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 4
- 229910052710 silicon Inorganic materials 0.000 description 3
- 239000010703 silicon Substances 0.000 description 3
- 239000004744 fabric Substances 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000007779 soft material Substances 0.000 description 2
- 239000003522 acrylic cement Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000004020 conductor Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000005291 magnetic effect Effects 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910021421 monocrystalline silicon Inorganic materials 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 239000004065 semiconductor Substances 0.000 description 1
- SBEQWOXEGHQIMW-UHFFFAOYSA-N silicon Chemical compound [Si].[Si] SBEQWOXEGHQIMW-UHFFFAOYSA-N 0.000 description 1
- 239000002210 silicon-based material Substances 0.000 description 1
- 229920002379 silicone rubber Polymers 0.000 description 1
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Abstract
A structure of a soft substrate of a plurality of micro-needles and a method for manufacturing the same, the structure mainly comprises needles and a soft substrate. Wherein the needle structure has a tip, a sidewall, and a base. And at the same time, the soft substrate is tightly wound on the side wall of the needle-shaped object and covers the surface of the needle-shaped object base opposite to the top end of the needle-shaped object. Because the structure uses the needle-shaped object matched with the soft base material, the sticking property is increased, the release of the back medicine is more facilitated, and the characteristic of large-area manufacture can be fully exerted.
Description
Invention field
The invention relates to a kind of array microneedle configuration and manufacture method thereof, particularly about a kind of array microneedle configuration and manufacture method thereof of using soft base material.
Background technology
MEMS is the emerging field that actively get involved countries in the world at present, so the definition of each department is all not quite identical, be called microsystems technology (Micro-system Technology in Europe, MST), its system that is defined as an intelligent microminiaturization comprises functions such as sensing, processing or actuating, comprises two or more electronics, machinery, optics, chemistry, biology, magnetics or other character and is incorporated on the single or multicore sheet.Be referred to as MEMS (Micro-electromechanical Systems in the U.S., MEMS), micromodule or system that it is defined as integration comprise the electronics and the machine components that utilize the compatible lots processed technology of IC to make, and the size of this assembly or system is from the micron to the millimeter.Then be called micromechanics (Micro-machines) in Japan, it is very little and can carry out the assembly of complicated small work, tool functional features to be defined as volume.
The present invention then is at proposing with the produced array type microneedle configuration of micro-electromechanical technology.And present so-called array type micropin is by certain technology the spicule array type to be arranged at structure on the hard substrate.Owing on each spicule, can be provided with perforate, or the spicule top layer is a conductive material, therefore often is applied to administering pharmaceutical substances paster or the little signal detecting of human body etc.
Therefore, known array declines needle construction promptly as described above, for mainly spicule being arranged on hard substrate, on silicon (silicon) or glass (glass), though existing micro-electromechanical technology can be with array type micropin size Control between 5～500 microns height, the known array structure that needle set has a hard substrate that declines has many puzzlements in utilization.
Please refer to Figure 1A, Figure 1A is the array type microneedle configuration figure of No. 20020082543, U.S. patent application case.In Figure 1A, the spicule 142 of array type microneedle configuration 100 promptly is arranged on (spicule 142 itself also is the silicon material usually) on the base material 132 that material is a silicon (silicon).Because this array type microneedle configuration 100 for using the base material 132 of hard, therefore when array type microneedle configuration 100 is used as the administering pharmaceutical substances paster, can cause medicine effectively to implant in the skin.
Its reason please refer to Figure 1B, and what Figure 1B illustrated is the rough schematic of array type microneedle configuration paster and contact skin.In Figure 1B, because the hard substrate 132 of array type microneedle configuration paster 100 fails to fit in fully on uneven skin 150 surfaces, and can't make that the entrained medicine of each spicule 142 top perforate (not shown) is all effectively implanted in the skin 150 on the base material 132.
Yet, use the array type microneedle configuration of hard substrate, bear uneven surface except being not suitable for pasting, also because of hard substrate relation own, cause inappropriate in other utilization.
Please refer to Fig. 2 A, Fig. 2 A is the microdevice rough schematic of No. 20020082545, U.S. patent application case.Microdevice 210 among Fig. 2 A is a kind of devices that medicine can be implanted in the skin 256.Wherein, be formed with a groove 240 on the base material 230, medicine can be inserted in the groove 240, and the top cover 220 of groove 240 be a kind of plastic materials, and have fingerstall 250 on the top cover 220.Therefore, when desire uses this microdevice 210 to implant medicine in the skin 256, need finger 264 stretched in the fingerstall 250 and exert pressure, force drug flow to cross the open-work 260 of 262 of base material 230 and spicules in spicule 262 top end openings 258 implantation skins 256 to point 264 pairs of top covers 220.
And in this microdevice 210, the open-work 260 that base material 230 and spicule are 262 forms and is not easy.When its reason was that spicule 262 is formed on the base material 230, spicule 262 syringe needle parts own can have perforate via micro electronmechanical technology, but spicule 262 perforates also need additional technique to form open-work with base material 230.Therefore, the open-work 260 that base material 230 and spicule are 262 forms and is not easy, and success rate is not high.
In addition, when 264 pairs of top covers 220 of finger were exerted pressure, except top cover 220 is subjected to the external force, base material 230 also was subjected to external force.Please refer to Fig. 2 B, Fig. 2 B illustrates is the rough schematic of Fig. 2 A base material 230 when being subjected to external force.Because in the micro electronmechanical technology of array type microneedle configuration, 230 silicon of often selecting for use of base material are a kind of crisp materials that belong to monocrystal silicon structure, so base material 230 is easy to be subjected to external impacts and destroys.And simultaneously,, will make base material 230 seem fragile more if microdevice 210 uses large-area base material 230.
Therefore, use the array type microneedle configuration of hard substrate to have following shortcoming really:
1. hard substrate can't have preferable pasting property.
2. be difficult for forming open-work between hard substrate and spicule.
3. hard substrate is subjected to external impacts and embrittlement easily.
4. hard substrate can't be applied on the large tracts of land because of fragile.
In view of this, the present invention proposes a kind of array type micropin soft base material structure and manufacture method thereof, except that the increase of pasting property, more helps drug release behind and can give full play to the characteristic of large-area manufacturing.
Summary of the invention
Main purpose of the present invention provides a kind of array type micropin soft base material structure, and it mainly comprises spicule and flexible substrate.Wherein said spicule structure has top, sidewall and base.And described flexible substrate is tightly around the sidewall setting of spicule and be covered on this spicule susceptor surface relative with the spicule top.
Provide to of the present invention syllabus another kind of array type micropin soft base material structure, also mainly comprise spicule and soft base material.But the spicule surface has the conductive layer that extends to the spicule base along the spicule sidewall, and flexible substrate is tightly around the sidewall setting of spicule and be covered on the spicule susceptor surface relative with the spicule top, and the distribution mode of flexible substrate just can make the conductive layer two ends expose with the conduction message.
In preferred embodiment of the present invention, array type micropin soft base material structure can specifically be selected different materials for use because of the difference utilization.The act spicule is an example, when array type micropin soft base material structure is used for administering pharmaceutical substances, can select for use the top to have the spicule of opening.
The last purpose of the present invention is to provide a kind of manufacture method of array type micropin soft base material structure, and it mainly comprises earlier on the spicule top, sidewall areas and carry out ion near the spicule base area of spicule sidewall and arrange.On the surface of spicule base relative and partial sidewall, be coated with flexible substrate then, so that flexible substrate tightly is distributed on the spicule base around the spicule sidewall with the spicule top.At last, the etching spicule is so that near being coated with flexible substrate on spicule sidewall and the spicule susceptor surface relative with the spicule top.
In preferred embodiment of the present invention, this manufacture method more is included in carries out before the ion layout, surface at the spicule sidewall, and the surface of the spicule base relative with the spicule top plates a conductive layer, is beneficial to signal is conducted to via the conductive layer on the spicule sidewall conductive layer of spicule base.
And the method that ion is arranged comprises coating one deck photoresist layer on spicule top, sidewall areas and base area surface earlier.The lip-deep photoresist of spicule base area to spicule top, sidewall areas and close spicule sidewall exposes then.At last the lip-deep photoresist of spicule top, sidewall areas and base area is developed, arrange to carry out ion.
Wherein, the method for photoresist coating also comprise utilize light shield definition spicule top, sidewall areas and near this spicule base area of this spicule sidewall so that the photoresist on a little region surface is exposed.
Carrying out the postpone of ion cloth as for this manufacture method, more comprising again to coating one deck photoresist on spicule top, sidewall areas and the close spicule base area surface of spicule sidewall.Then the lip-deep photoresist of spicule base area is exposed, develops, on the spicule base area surface relative, to be coated with flexible substrate with the spicule top.
Concrete ion involved in the present invention is arranged, etching technique all is conventional techniques of this area, and this paper is not described in detail at this point.
Comprehensively above-mentioned, the present invention proposes a kind of array type micropin soft base material structure and manufacture method thereof, by combining of spicule and flexible material substrate, except that can increasing its pasting property, more help drug release behind and can give full play to the characteristic of large-area manufacturing.
Description of drawings
Figure 1A is the array type microneedle configuration figure of No. 20020082543, U.S. patent application case;
Figure 1B is the rough schematic of array type microneedle configuration paster and contact skin;
Fig. 2 A is the microdevice rough schematic of No. 20020082545, U.S. patent application case;
Fig. 2 B is the rough schematic of Fig. 2 A base material 230 when being subjected to external force;
Fig. 3 A, Fig. 3 B are respectively the rough schematic and the simple application figure of the array micropin soft base material structure in the preferred embodiment of the present invention; And
Fig. 4 A～I is preferred embodiment of the present invention, can help the rough schematic of the array type micropin soft base material structural manufacturing process flow process of behind drug release and human body signal measurement simultaneously.
The figure number explanation: 142,262,310,400: spicule 132,230,320: base material 100,300,490: array type microneedle configuration 150,256: skin 210: microdevice 240: groove 220: top cover 250: fingerstall 260,495: open-work 258,405: the spicule top opens 264: finger 330: uneven surperficial 403: spicule top 410: spicule sidewall 430: spicule base 455: light shield 450,460: photoresist 465: conductive layer 467: flexible material.
The specific embodiment
The present invention is described in detail with instantiation below in conjunction with accompanying drawing, so that the present invention is had more deep understanding.
The present invention is based on the selected single crystal silicon substrate of present array type microneedle configuration and belong to crisp material, except that being easy to because of the impact of external force the embrittlement, and this array type micropin hard substrate structure applications has the puzzlement that pasting property is not good, open-work is difficult for formation, large-area manufacturing is difficult for when patch system.In addition, the patch system of pin row micropin hard substrate structure is aspect administering pharmaceutical substances, and for medicine being put into perforate inside, spicule top reaching administering pharmaceutical substances, but its type of drive and capacity also are difficult technology.Therefore the present invention's conception is with the base material of flexible material as the array type microneedle configuration, by combining of spicule and flexible substrate, provides back side administering pharmaceutical substances or health check-up collection to reach, and for the application of array type microneedle configuration greater room arranged.
Please also refer to Fig. 3 A and Fig. 3 B, Fig. 3 A, Fig. 3 B are respectively the rough schematic and the simple application figure of the array micropin soft base material structure in the preferred embodiment of the present invention.When array type microneedle configuration 300 among Fig. 3 A spicule 310 is arranged on soft base material 320 as silica gel (Silicon Rubber), acryl glue (PMMA), polydimethylsiloxane (PDMS), polyethylene (PE), polypropylene polymeric materials such as (PP) on the time, because pin row microneedle configuration 300 freely deformables, therefore array type microneedle configuration 300 can be covered on the picture skin uneven surperficial 330 shown in Fig. 3 B easily.
The present invention can adopt different spicule structure collocation soft base materials because of different demands except the base material of main use soft material as the array type microneedle configuration.For instance, be used for the array type micropin soft base material structure of administering pharmaceutical substances behind, its spicule structure is for having the mouth of doing, so that medicine is seen through behind by base material and discharges through the spicule opening on its top.Again for instance, if be used for the array type micropin soft base material structure that the human body signal is measured, its spicule structure is for to be coated with conductive layer on its sidewall and susceptor surface, so that the human body signal can conduct to the output of spicule base via the spicule sidewall.
Therefore, the present invention is except different with the array type microneedle configuration of known use hard substrate, and array type microneedle configuration of the present invention uses the technology of soft base material also different along with demand.
Please refer to Fig. 4 A～I, Fig. 4 A～I is preferred embodiment of the present invention, can help the rough schematic of the array type micropin soft base material structural manufacturing process flow process of behind drug release and human body signal measurement simultaneously.At first shown in Fig. 4 A, 403 spicule 400 surfaces with opening 405 plate conductive layer 465 in the evaporation mode on the top, as metal level.And conductive layer 465 is extended on the surface 440 of spicule 400 bases 430 by spicule 400 sidewalls 410 surfaces 420, so that the human body signal in the future can be via the two ends conduction of conductive layer 465 on the spicule 400.
Afterwards, prepare on spicule 400 tops 403, sidewall 410 zones and carry out ion near spicule base 430 zones of spicule sidewalls 410 and arrange, to form spicule 400 outward appearance after a while.
Be familiar with this skill person as can be known, this regional ion arranges, can through as last photoresist, exposure in the semiconductor technology, develop, go step such as photoresist to finish.Therefore, can be shown in Fig. 4 B, coating one deck photoresist 450 on spicule 400 surfaces utilizes light shield 455 to limit the post-exposure of ion layout area then earlier.To the left next structure in the back of exposing, shown in Fig. 4 C, carry out ion and arrange again.And the photoresist on the spicule 400 is removed in the postpone of ion cloth, and promptly shown in Fig. 4 D, spicule 400 is only accepted ion and arranged in top 403, sidewall 410 zones and close base 430 zones of sidewall 410.
Then, coating one deck flexible material and manages to make flexible material tightly to distribute around the conductive layer on spicule 400 sidewalls as base material on spicule 400 bases 430 surfaces relative with spicule 400 tops 403 and on this surperficial conductive layer.This practice also can be firmly attached on the spicule 400 for making flexible material as spicule 400 base materials simultaneously.For finishing this technology, shown in Fig. 4 E, can utilize mode earlier as Fig. 4 C, on spicule 403 zones, 400 tops and sidewall 410 subregions, form one deck photoresist 460.For another example shown in Fig. 4 F, on spicule 400 bases 430 surfaces (comprise this surperficial conductive layer) relative with spicule 400 tops 403 and partial sidewall 410 conductive layers 465 surfaces go up coating one deck flexible materials 467 as base material, and after a while photoresist 460 is removed from spicule 400, to form shape shown in Fig. 4 G.
At last, when the tight conductive layer 465 and when being distributed on the base 430 on sidewall 410 subregions of the flexible material on the spicule 400, spicule 400 is carried out etching.Since 400 of spicules in the top 403, sidewall 410 zones and have ion near base 430 zones of sidewalls 410 and arrange, therefore when spicule 400 itself is carried out etching, there is the ion layout area different etch-rates just to be arranged in spicule 400 bases 430 with no ion layout area.Be to have the etch-rate of ion layout area slower in spicule 400 bases 430, and the etch-rate of no ion layout area is very fast in spicule 400 bases 430.
And after spicule 400 etchings finish, the zone that no ion is arranged in spicule 400 bases 430 is by etching fully, only stay the zone that ion is arranged, and shown in Fig. 4 h, form the array type micropin soft base material structure 490 that the last institute of preferred embodiment of the present invention desire forms.
Therefore, these array type micropin soft base material structure 490 characteristics in the preferred embodiment of the present invention are:
1. this array type micropin soft base material structure 490 is mainly combining of spicule 400 and soft base material 467, applicable to various surface.
2. has conductive layer 465 on the spicule, and the two ends of spicule 400 conductive layers are exposed to respectively between spicule 400 sidewalls 410 and flexible substrate 467 and the base 430, and the two ends of conductive layer 465 can be respectively applied for detecting and derive as the signal of human body etc. and with signal.
3. if increase the etching period of Fig. 4 G, can form shown in Fig. 4 I, form open-work 495, to finish administering pharmaceutical substances behind on spicule 400 tops 403 and 430 of bases.
4. because the present invention uses soft material as base material, so the present invention is when being made as large tracts of land, and the situation that does not have easy embrittlement takes place.
Comprehensively above-mentioned, the present invention proposes a kind of array type micropin soft base material structure and manufacture method thereof, use soft base material combine with spicule, except that its pasting property of increase, more help the behind drug release and can give full play to the characteristic of large-area manufacturing to form the array microneedle configuration.
The above only is preferred embodiment of the present invention, and when not limiting scope of the invention process, all equalizations of doing according to claim of the present invention change and modify, and all should still belong to protection scope of the present invention.
Claims (10)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031370276A CN1321706C (en) | 2003-05-29 | 2003-05-29 | An array type microneedle soft substrate structure and its manufacturing method |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031370276A CN1321706C (en) | 2003-05-29 | 2003-05-29 | An array type microneedle soft substrate structure and its manufacturing method |
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| Publication Number | Publication Date |
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| CN1552476A CN1552476A (en) | 2004-12-08 |
| CN1321706C true CN1321706C (en) | 2007-06-20 |
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| CN108784670B (en) * | 2018-06-08 | 2019-09-20 | 清华大学 | Flexible adsorption device and manufacturing method thereof |
| CN111298280B (en) * | 2018-12-11 | 2024-04-12 | 尹忠 | Soft back microneedle and manufacturing method thereof |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000074765A1 (en) * | 1999-06-09 | 2000-12-14 | The Procter & Gamble Company | Intracutaneous microneedle array apparatus |
| CN1281377A (en) * | 1997-12-11 | 2001-01-24 | 阿尔扎有限公司 | Device for enhancing transdermal agent flux |
| US20020082543A1 (en) * | 2000-12-14 | 2002-06-27 | Jung-Hwan Park | Microneedle devices and production thereof |
| JP2002239014A (en) * | 2001-02-19 | 2002-08-27 | Sumitomo Precision Prod Co Ltd | Needle-like body and method for manufacturing needle- like body |
| US20020133129A1 (en) * | 2001-03-14 | 2002-09-19 | Francisco Arias | Method of manufacturing microneedle structures using soft lithography and photolithography |
| EP1287847A1 (en) * | 2001-07-09 | 2003-03-05 | Lifescan, Inc. | Improved micro-needles and methods of manufacture and use thereof |
-
2003
- 2003-05-29 CN CNB031370276A patent/CN1321706C/en not_active Expired - Fee Related
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1281377A (en) * | 1997-12-11 | 2001-01-24 | 阿尔扎有限公司 | Device for enhancing transdermal agent flux |
| WO2000074765A1 (en) * | 1999-06-09 | 2000-12-14 | The Procter & Gamble Company | Intracutaneous microneedle array apparatus |
| US20020082543A1 (en) * | 2000-12-14 | 2002-06-27 | Jung-Hwan Park | Microneedle devices and production thereof |
| JP2002239014A (en) * | 2001-02-19 | 2002-08-27 | Sumitomo Precision Prod Co Ltd | Needle-like body and method for manufacturing needle- like body |
| US20020133129A1 (en) * | 2001-03-14 | 2002-09-19 | Francisco Arias | Method of manufacturing microneedle structures using soft lithography and photolithography |
| EP1287847A1 (en) * | 2001-07-09 | 2003-03-05 | Lifescan, Inc. | Improved micro-needles and methods of manufacture and use thereof |
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| CN1552476A (en) | 2004-12-08 |
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