CN109893754A - A kind of hollow structure microneedle array production method with outer layer - Google Patents
A kind of hollow structure microneedle array production method with outer layer Download PDFInfo
- Publication number
- CN109893754A CN109893754A CN201910323058.2A CN201910323058A CN109893754A CN 109893754 A CN109893754 A CN 109893754A CN 201910323058 A CN201910323058 A CN 201910323058A CN 109893754 A CN109893754 A CN 109893754A
- Authority
- CN
- China
- Prior art keywords
- pdms
- microneedle array
- outer layer
- mold
- mould
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Media Introduction/Drainage Providing Device (AREA)
Abstract
The hollow structure microneedle array production method with outer layer that the invention discloses a kind of, including following operating procedure: S1: original silicon mould is made；S2: by original silicon mould silanization, configuring PDMS solution by 10:1, and silicon wafer is pasted with double-sided adhesive and in culture dish, pours into configured PDMS solution, pumping bubble 25-35min；S3: by the original silicon mould in S2 step, heat cure 1-3h, demoulding obtain two pieces of aciculiform PDMS molds in 50 DEG C of -70 DEG C of baking ovens；S4: by the big aciculiform PDMS mould secondary revolving die of size, hole shape larger size PDMS mold is obtained；S5: filling larger size cheats shape PDMS mold, obtains microneedle array structure；S6: it is demoulded after being taken out after microneedle array structure abstraction bubble；S7: aperture is outputed below microneedle array structure.Through the above way, there are the hollow microneedle arrays of outer layer in the present invention, outer layer and hollow space size adjustable are whole, outer layer can be prepared as degradable, solid and hole structure according to demand, meet more scene application needs, the effective component of diversified forms can be filled to reach the requirement for meeting different application scene in hollow hole.
Description
Technical field
The present invention relates to a kind of microneedle arrays, more particularly to the hollow structure microneedle array production method for having outer layer.
Background technique
With the progress of micrometer-nanometer processing technology, the device of micron-submicron scale constantly obtains the favor of society, with micro-
The microneedle array of fining-off technology preparation is widely used in cutaneous penetration field due to Micro trauma, minimally invasive, micro- pain
Research.New delivering mode is provided for hydroaropic substance, macromolecular, protein-based, vaccine and targeted drug, it is slow in drug
It releases, controlled release, fine-grained management aspect have critical role.
It, can be in the neck such as tissue sampling, sensing, disease diagnosis and therapy, beauty with micropin prepared by biocompatible material
Domain application.
Based on solid, dissolvable and hollow microneedles, the preparation of hollow microneedles depends on complicated and high the type of micropin more
The repeatability of expensive process equipment, technique is poor.Stratiform micropin is mostly to pass through centrifugation protocol to be layered along micropin short transverse.
The preparation of empty micropin proposed by the present invention with outer layer, outer layer are selected along micropin horizontal direction by material,
Outer layer can be prepared as to dissolvable layer or runner is formed by cutting.
Summary of the invention
The present invention solves the technical problem of how to provide ni au hard rock microneedle array designed by one kind with nothing
Damage, high-intensitive, easy-operating advantage, Diamond tip help that quantum nanoparticles sensing is made to become more cost effective and practical
Property, it can also be used to carry out the hollow structure with outer layer of the highly sensitive nanometer measurement of such as electromagnetic field, temperature or stress
Microneedle array production method.
In order to solve the above technical problems, one technical scheme adopted by the invention is that: it provides a kind of with the hollow of outer layer
Structure microneedle array production method, the hollow structure microneedle array production method with outer layer include following operation step
It is rapid:
S1: original silicon mould is made；
S2: by original silicon mould silanization, configuring PDMS solution by 10:1, by silicon wafer with double-sided adhesive paste in culture dish,
Enter configured PDMS solution, pumping bubble 25-35min；
S3: by the original silicon mould in S2 step, heat cure 1-3h, demoulding obtain two pieces of aciculiforms in 50 DEG C of -70 DEG C of baking ovens
PDMS mold；
S4: by the big aciculiform PDMS mould secondary revolving die of size, hole shape larger size PDMS mold is obtained；
S5: using one of HA, PVA, PVP, PDMS or a variety of, filling larger size cheats shape PDMS mold respectively, uses alignment
Label finds alignment point, and selects proper height boss control back seat thickness degree and outer layer thickness, obtains microneedle array structure；
S6: extracting bubble for the microneedle array structure in S5 step, and keeps in 50 DEG C of -70 DEG C of baking ovens to drying, takes out
After demould；
S7: by cutting, laser boring and grinding technics, aperture is outputed below microneedle array structure.
In a specific embodiment, including following operating procedure:
S1: original silicon mould is made；
S2: by original silicon mould silanization, configuring PDMS solution by 10:1, by silicon wafer with double-sided adhesive paste in culture dish,
Enter configured PDMS solution, pumping bubble 30min；
S3: by the original silicon mould in S2 step, heat cure 2.5h, demoulding obtain two pieces of aciculiform PDMS moulds in 65 DEG C of baking ovens
Tool；
S4: by the big aciculiform PDMS mould secondary revolving die of size, hole shape larger size PDMS mold is obtained；
S5: using one of HA, PVA, PVP, PDMS or a variety of, filling larger size cheats shape PDMS mold respectively, uses alignment
Label finds alignment point, and selects proper height boss control back seat thickness degree and outer layer thickness, obtains microneedle array structure；
S6: extracting bubble for the microneedle array structure in S5 step, and keeps in 60 ° of baking ovens to drying, demoulds after taking-up；
S7: by cutting, laser boring and grinding technics, aperture is outputed below microneedle array structure.
In a specific embodiment, in step sl, the making step of original silicon mould is as follows:
A: two pieces of the work in coordination aciculiform used and hole shape molds are selected, the hollow microneedle arrays with outer layer are prepared；
B: in a, selecting crystal orientation is the silicon dioxide substrate of<100>, two-sided spin coating 5um photoresist；
C: in b, after silicon dioxide substrate mask, exposure, development, BOE solution etches window silicon dioxide layer, removal are used
5um photoresist；
D: in step c, using silicon dioxide layer surface residual positive photoetching rubber as exposure mask, etching liquid is buffered using BOE, etches dioxy
SiClx layer, after the completion hot pressing SU-8 dry film；
E: using the silicon dioxide layer etching depth in step instrument monitoring S4 step, until stop when silicon face,
F: removing photoresist using acetone, clean, drying；
The aciculiform and hole shape mold have alignment mark, with guarantee two pieces of molds can alignment correction, height can be placed between mold
Spend different boss.
In a specific embodiment, the microneedle array mold shape be cone, pyramid shape, triangular pyramid or
Cylindricality.
In a specific embodiment, the BOE buffers etching liquid KOH solution, in step d, prepares mass fraction
The KOH solution of 70-90%, maintains 80=90 degrees Celsius using magnetic heating stirrer, clamps silicon wafer using fixture, tilts 30-
50 °, etch 1.5-2.5h.
In a specific embodiment, the BOE buffers etching liquid KOH solution, in step d, prepares mass fraction
80% KOH solution, maintains 85 degrees Celsius using magnetic heating stirrer, clamps silicon wafer using fixture, tilts 45 °, etches 2h.
In a specific embodiment, after micro- sem observation confirms and obtains the cone hole that apex angle is 54.7 °, select SU-8 dry
Film, using heat-laminator press mold, front baking is connect except protective film.
In a specific embodiment, exposure parameter is determined by thickness using litho machine, and exposed using mask plate exposure mask
Light.
The beneficial effects of the present invention are: there is the hollow microneedle arrays of outer layer, outer layer and hollow space size adjustable are whole, outer layer
It can be prepared as degradable, solid and hole structure according to demand, meet more scene application needs, diversified forms can be filled in hollow hole
Effective component with up to meeting the requirement of different application scene.
Detailed description of the invention
To describe the technical solutions in the embodiments of the present invention more clearly, make required in being described below to embodiment
Attached drawing is briefly described, it should be apparent that, drawings in the following description are only some embodiments of the invention, for
For those of ordinary skill in the art, without creative efforts, it can also be obtained according to these attached drawings other
Attached drawing, in which:
Fig. 1 is original silicon mould of the present invention with a specific embodiment in the hollow structure microneedle array production method of outer layer；
Fig. 2 is that the band prepared of the present invention with a specific embodiment in the hollow structure microneedle array production method of outer layer is outer
The hollow microneedles structural schematic diagram of layer；
Fig. 3 is that the band prepared of the present invention with a specific embodiment in the hollow structure microneedle array production method of outer layer is outer
The hollow microneedles structural profile illustration of layer；
It is marked in tool as follows: 1, aciculiform mold；2, shape mold is cheated.
Specific embodiment
The technical scheme in the embodiments of the invention will be clearly and completely described below, it is clear that described implementation
Example is only a part of the embodiments of the present invention, instead of all the embodiments.Based on the embodiments of the present invention, this field is common
Technical staff's all other embodiment obtained without making creative work belongs to the model that the present invention protects
It encloses.
Attached drawing is please referred to, a kind of hollow structure micropin battle array with outer layer is provided in one particular embodiment of the present invention
Column production method,
Embodiment 1:
A kind of hollow structure microneedle array production method with outer layer, the hollow structure microneedle array system with outer layer
Include following operating procedure as method:
S1: original silicon mould is made；
S2: by original silicon mould silanization, configuring PDMS solution by 10:1, by silicon wafer with double-sided adhesive paste in culture dish,
Enter configured PDMS solution, pumping bubble 25-35min；
S3: by the original silicon mould in S2 step, heat cure 1-3h, demoulding obtain two pieces of aciculiforms in 50 DEG C of -70 DEG C of baking ovens
PDMS mold；
S4: by the big aciculiform PDMS mould secondary revolving die of size, hole shape larger size PDMS mold is obtained；
S5: using one of HA, PVA, PVP, PDMS or a variety of, filling larger size cheats shape PDMS mold respectively, uses alignment
Label finds alignment point, and selects proper height boss control back seat thickness degree and outer layer thickness, obtains microneedle array structure；
S6: extracting bubble for the microneedle array structure in S5 step, and keeps in 50 DEG C of -70 DEG C of baking ovens to drying, takes out
After demould；
S7: by cutting, laser boring and grinding technics, aperture is outputed below microneedle array structure.
Embodiment 2:
A kind of hollow structure microneedle array production method with outer layer, the hollow structure microneedle array system with outer layer
Include following operating procedure as method:
S1: original silicon mould is made；
S2: by original silicon mould silanization, configuring PDMS solution by 10:1, by silicon wafer with double-sided adhesive paste in culture dish,
Enter configured PDMS solution, pumping bubble 30min；
S3: by the original silicon mould in S2 step, heat cure 2.5h, demoulding obtain two pieces of aciculiform PDMS moulds in 65 DEG C of baking ovens
Tool；
S4: by the big aciculiform PDMS mould secondary revolving die of size, hole shape larger size PDMS mold is obtained；
S5: using one of HA, PVA, PVP, PDMS or a variety of, filling larger size cheats shape PDMS mold respectively, uses alignment
Label finds alignment point, and selects proper height boss control back seat thickness degree and outer layer thickness, obtains microneedle array structure；
S6: extracting bubble for the microneedle array structure in S5 step, and keeps in 60 ° of baking ovens to drying, demoulds after taking-up；
S7: by cutting, laser boring and grinding technics, aperture is outputed below microneedle array structure.
Embodiment 3:
A kind of hollow structure microneedle array production method with outer layer, the hollow structure microneedle array system with outer layer
Include following operating procedure as method:
S1: original silicon mould is made；
S2: by original silicon mould silanization, configuring PDMS solution by 10:1, by silicon wafer with double-sided adhesive paste in culture dish,
Enter configured PDMS solution, pumping bubble 30min；
S3: by the original silicon mould in S2 step, heat cure 2.5h, demoulding obtain two pieces of aciculiform PDMS moulds in 65 DEG C of baking ovens
Tool；
S4: by the big aciculiform PDMS mould secondary revolving die of size, hole shape larger size PDMS mold is obtained；
S5: using one of HA, PVA, PVP, PDMS or a variety of, filling larger size cheats shape PDMS mold respectively, uses alignment
Label finds alignment point, and selects proper height boss control back seat thickness degree and outer layer thickness, obtains microneedle array structure；
S6: extracting bubble for the microneedle array structure in S5 step, and keeps in 60 ° of baking ovens to drying, demoulds after taking-up；
S7: by cutting, laser boring and grinding technics, aperture is outputed below microneedle array structure.
In step sl, the making step of original silicon mould is as follows:
A: two pieces of the work in coordination aciculiform used and hole shape molds are selected, the hollow microneedle arrays with outer layer are prepared；
B: in a, selecting crystal orientation is the silicon dioxide substrate of<100>, two-sided spin coating 5um photoresist；
C: in b, after silicon dioxide substrate mask, exposure, development, BOE solution etches window silicon dioxide layer, removal are used
5um photoresist；
D: in step c, using silicon dioxide layer surface residual positive photoetching rubber as exposure mask, etching liquid is buffered using BOE, etches dioxy
SiClx layer, after the completion hot pressing SU-8 dry film；
E: using the silicon dioxide layer etching depth in step instrument monitoring S4 step, until stop when silicon face,
F: removing photoresist using acetone, clean, drying；
The aciculiform and hole shape mold have alignment mark, with guarantee two pieces of molds can alignment correction, height can be placed between mold
Spend different boss.
Embodiment 4:
A kind of hollow structure microneedle array production method with outer layer, the hollow structure microneedle array system with outer layer
Include following operating procedure as method:
S1: original silicon mould is made；
S2: by original silicon mould silanization, configuring PDMS solution by 10:1, by silicon wafer with double-sided adhesive paste in culture dish,
Enter configured PDMS solution, pumping bubble 30min；
S3: by the original silicon mould in S2 step, heat cure 2.5h, demoulding obtain two pieces of aciculiform PDMS moulds in 65 DEG C of baking ovens
Tool；
S4: by the big aciculiform PDMS mould secondary revolving die of size, hole shape larger size PDMS mold is obtained；
S5: using one of HA, PVA, PVP, PDMS or a variety of, filling larger size cheats shape PDMS mold respectively, uses alignment
Label finds alignment point, and selects proper height boss control back seat thickness degree and outer layer thickness, obtains microneedle array structure；
S6: extracting bubble for the microneedle array structure in S5 step, and keeps in 60 ° of baking ovens to drying, demoulds after taking-up；
S7: by cutting, laser boring and grinding technics, aperture is outputed below microneedle array structure.
In step sl, the making step of original silicon mould is as follows:
A: two pieces of the work in coordination aciculiform used and hole shape molds are selected, the hollow microneedle arrays with outer layer are prepared；
B: in a, selecting crystal orientation is the silicon dioxide substrate of<100>, two-sided spin coating 5um photoresist；
C: in b, after silicon dioxide substrate mask, exposure, development, BOE solution etches window silicon dioxide layer, removal are used
5um photoresist；
D: in step c, using silicon dioxide layer surface residual positive photoetching rubber as exposure mask, etching liquid is buffered using BOE, etches dioxy
SiClx layer, after the completion hot pressing SU-8 dry film；
E: using the silicon dioxide layer etching depth in step instrument monitoring S4 step, until stop when silicon face,
F: removing photoresist using acetone, clean, drying；
The aciculiform and hole shape mold have alignment mark, with guarantee two pieces of molds can alignment correction, height can be placed between mold
Spend different boss.
The microneedle array mold shape is cone, pyramid shape, triangular pyramid or cylindricality.
Embodiment 5:
A kind of hollow structure microneedle array production method with outer layer, the hollow structure microneedle array system with outer layer
Include following operating procedure as method:
S1: original silicon mould is made；
S2: by original silicon mould silanization, configuring PDMS solution by 10:1, by silicon wafer with double-sided adhesive paste in culture dish,
Enter configured PDMS solution, pumping bubble 30min；
S3: by the original silicon mould in S2 step, heat cure 2.5h, demoulding obtain two pieces of aciculiform PDMS moulds in 65 DEG C of baking ovens
Tool；
S4: by the big aciculiform PDMS mould secondary revolving die of size, hole shape larger size PDMS mold is obtained；
S5: using one of HA, PVA, PVP, PDMS or a variety of, filling larger size cheats shape PDMS mold respectively, uses alignment
Label finds alignment point, and selects proper height boss control back seat thickness degree and outer layer thickness, obtains microneedle array structure；
S6: extracting bubble for the microneedle array structure in S5 step, and keeps in 60 ° of baking ovens to drying, demoulds after taking-up；
S7: by cutting, laser boring and grinding technics, aperture is outputed below microneedle array structure.
In step sl, the making step of original silicon mould is as follows:
A: two pieces of the work in coordination aciculiform used and hole shape molds are selected, the hollow microneedle arrays with outer layer are prepared；
B: in a, selecting crystal orientation is the silicon dioxide substrate of<100>, two-sided spin coating 5um photoresist；
C: in b, after silicon dioxide substrate mask, exposure, development, BOE solution etches window silicon dioxide layer, removal are used
5um photoresist；
D: in step c, using silicon dioxide layer surface residual positive photoetching rubber as exposure mask, etching liquid is buffered using BOE, etches dioxy
SiClx layer, after the completion hot pressing SU-8 dry film；
E: using the silicon dioxide layer etching depth in step instrument monitoring S4 step, until stop when silicon face,
F: removing photoresist using acetone, clean, drying；
The aciculiform and hole shape mold have alignment mark, with guarantee two pieces of molds can alignment correction, height can be placed between mold
Spend different boss.
The microneedle array mold shape is cone, pyramid shape, triangular pyramid or cylindricality.
The BOE buffers etching liquid KOH solution, in step d, prepares the KOH solution of mass fraction 70-90%, uses
Magnetic heating stirrer maintains 80=90 degrees Celsius, clamps silicon wafer using fixture, tilts 30-50 °, etches 1.5-2.5h.
Embodiment 6:
A kind of hollow structure microneedle array production method with outer layer, the hollow structure microneedle array system with outer layer
Include following operating procedure as method:
S1: original silicon mould is made；
S2: by original silicon mould silanization, configuring PDMS solution by 10:1, by silicon wafer with double-sided adhesive paste in culture dish,
Enter configured PDMS solution, pumping bubble 30min；
S3: by the original silicon mould in S2 step, heat cure 2.5h, demoulding obtain two pieces of aciculiform PDMS moulds in 65 DEG C of baking ovens
Tool；
S4: by the big aciculiform PDMS mould secondary revolving die of size, hole shape larger size PDMS mold is obtained；
S5: using one of HA, PVA, PVP, PDMS or a variety of, filling larger size cheats shape PDMS mold respectively, uses alignment
Label finds alignment point, and selects proper height boss control back seat thickness degree and outer layer thickness, obtains microneedle array structure；
S6: extracting bubble for the microneedle array structure in S5 step, and keeps in 60 ° of baking ovens to drying, demoulds after taking-up；
S7: by cutting, laser boring and grinding technics, aperture is outputed below microneedle array structure.
In step sl, the making step of original silicon mould is as follows:
A: two pieces of the work in coordination aciculiform used and hole shape molds are selected, the hollow microneedle arrays with outer layer are prepared；
B: in a, selecting crystal orientation is the silicon dioxide substrate of<100>, two-sided spin coating 5um photoresist；
C: in b, after silicon dioxide substrate mask, exposure, development, BOE solution etches window silicon dioxide layer, removal are used
5um photoresist；
D: in step c, using silicon dioxide layer surface residual positive photoetching rubber as exposure mask, etching liquid is buffered using BOE, etches dioxy
SiClx layer, after the completion hot pressing SU-8 dry film；
E: using the silicon dioxide layer etching depth in step instrument monitoring S4 step, until stop when silicon face,
F: removing photoresist using acetone, clean, drying；
The aciculiform and hole shape mold have alignment mark, with guarantee two pieces of molds can alignment correction, height can be placed between mold
Spend different boss.
The microneedle array mold shape is cone, pyramid shape, triangular pyramid or cylindricality.
The BOE buffers etching liquid KOH solution, in step d, prepares the KOH solution of mass fraction 70-90%, uses
Magnetic heating stirrer maintains 80=90 degrees Celsius, clamps silicon wafer using fixture, tilts 30-50 °, etches 1.5-2.5h.
The BOE buffers etching liquid KOH solution, in step d, prepares the KOH solution of mass fraction 80%, uses magnetic
Power heating stirrer maintains 85 degrees Celsius, clamps silicon wafer using fixture, tilts 45 °, etches 2h.
Embodiment 7:
A kind of hollow structure microneedle array production method with outer layer, the hollow structure microneedle array system with outer layer
Include following operating procedure as method:
S1: original silicon mould is made；
S2: by original silicon mould silanization, configuring PDMS solution by 10:1, by silicon wafer with double-sided adhesive paste in culture dish,
Enter configured PDMS solution, pumping bubble 30min；
S3: by the original silicon mould in S2 step, heat cure 2.5h, demoulding obtain two pieces of aciculiform PDMS moulds in 65 DEG C of baking ovens
Tool；
S4: by the big aciculiform PDMS mould secondary revolving die of size, hole shape larger size PDMS mold is obtained；
S5: using one of HA, PVA, PVP, PDMS or a variety of, filling larger size cheats shape PDMS mold respectively, uses alignment
Label finds alignment point, and selects proper height boss control back seat thickness degree and outer layer thickness, obtains microneedle array structure；
S6: extracting bubble for the microneedle array structure in S5 step, and keeps in 60 ° of baking ovens to drying, demoulds after taking-up；
S7: by cutting, laser boring and grinding technics, aperture is outputed below microneedle array structure.
In step sl, the making step of original silicon mould is as follows:
A: two pieces of the work in coordination aciculiform used and hole shape molds are selected, the hollow microneedle arrays with outer layer are prepared；
B: in a, selecting crystal orientation is the silicon dioxide substrate of<100>, two-sided spin coating 5um photoresist；
C: in b, after silicon dioxide substrate mask, exposure, development, BOE solution etches window silicon dioxide layer, removal are used
5um photoresist；
D: in step c, using silicon dioxide layer surface residual positive photoetching rubber as exposure mask, etching liquid is buffered using BOE, etches dioxy
SiClx layer, after the completion hot pressing SU-8 dry film；
E: using the silicon dioxide layer etching depth in step instrument monitoring S4 step, until stop when silicon face,
F: removing photoresist using acetone, clean, drying；
The aciculiform and hole shape mold have alignment mark, with guarantee two pieces of molds can alignment correction, height can be placed between mold
Spend different boss.
The microneedle array mold shape is cone, pyramid shape, triangular pyramid or cylindricality.
The BOE buffers etching liquid KOH solution, in step d, prepares the KOH solution of mass fraction 70-90%, uses
Magnetic heating stirrer maintains 80=90 degrees Celsius, clamps silicon wafer using fixture, tilts 30-50 °, etches 1.5-2.5h.
The BOE buffers etching liquid KOH solution, in step d, prepares the KOH solution of mass fraction 80%, uses magnetic
Power heating stirrer maintains 85 degrees Celsius, clamps silicon wafer using fixture, tilts 45 °, etches 2h.
After micro- sem observation confirms and obtains the cone hole that apex angle is 54.7 °, SU-8 dry film is selected, heat-laminator pressure is used
Film, front baking connect except protective film.
Embodiment 8:
A kind of hollow structure microneedle array production method with outer layer, the hollow structure microneedle array system with outer layer
Include following operating procedure as method:
S1: original silicon mould is made；
S2: by original silicon mould silanization, configuring PDMS solution by 10:1, by silicon wafer with double-sided adhesive paste in culture dish,
Enter configured PDMS solution, pumping bubble 30min；
S3: by the original silicon mould in S2 step, heat cure 2.5h, demoulding obtain two pieces of aciculiform PDMS moulds in 65 DEG C of baking ovens
Tool；
S4: by the big aciculiform PDMS mould secondary revolving die of size, hole shape larger size PDMS mold is obtained；
S5: using one of HA, PVA, PVP, PDMS or a variety of, filling larger size cheats shape PDMS mold respectively, uses alignment
Label finds alignment point, and selects proper height boss control back seat thickness degree and outer layer thickness, obtains microneedle array structure；
S6: extracting bubble for the microneedle array structure in S5 step, and keeps in 60 ° of baking ovens to drying, demoulds after taking-up；
S7: by cutting, laser boring and grinding technics, aperture is outputed below microneedle array structure.
In step sl, the making step of original silicon mould is as follows:
A: two pieces of the work in coordination aciculiform used and hole shape molds are selected, the hollow microneedle arrays with outer layer are prepared；
B: in a, selecting crystal orientation is the silicon dioxide substrate of<100>, two-sided spin coating 5um photoresist；
C: in b, after silicon dioxide substrate mask, exposure, development, BOE solution etches window silicon dioxide layer, removal are used
5um photoresist；
D: in step c, using silicon dioxide layer surface residual positive photoetching rubber as exposure mask, etching liquid is buffered using BOE, etches dioxy
SiClx layer, after the completion hot pressing SU-8 dry film；
E: using the silicon dioxide layer etching depth in step instrument monitoring S4 step, until stop when silicon face,
F: removing photoresist using acetone, clean, drying；
The aciculiform and hole shape mold have alignment mark, with guarantee two pieces of molds can alignment correction, height can be placed between mold
Spend different boss.
The microneedle array mold shape is cone, pyramid shape, triangular pyramid or cylindricality.
The BOE buffers etching liquid KOH solution, in step d, prepares the KOH solution of mass fraction 70-90%, uses
Magnetic heating stirrer maintains 80=90 degrees Celsius, clamps silicon wafer using fixture, tilts 30-50 °, etches 1.5-2.5h.
The BOE buffers etching liquid KOH solution, in step d, prepares the KOH solution of mass fraction 80%, uses magnetic
Power heating stirrer maintains 85 degrees Celsius, clamps silicon wafer using fixture, tilts 45 °, etches 2h.
After micro- sem observation confirms and obtains the cone hole that apex angle is 54.7 °, SU-8 dry film is selected, heat-laminator pressure is used
Film, front baking connect except protective film.
Exposure parameter is determined by thickness using litho machine, and uses mask plate mask exposure.
In above-described embodiment, the hole shape larger size PDMS mold is hole shape mold.
In the specific implementation process, it can be aligned using two pieces, micropin mold preparation of different sizes is with dissolvable outer
The production method of the microneedle array of layer and hollow space.Through exposure mask, development, wet etching two in two pieces of silicon silicon dioxide substrates
The techniques such as silica, wet etching silicon form the different cone hole of side length, rear to select SU-8 dry film material attachment above silicon substrate,
The SU-8 glue in development removal cone hole, forms two pieces of pit type female molds after ultraviolet photolithographic machine photoetching.PDMS is poured into rear mold, is taken out
The bubble in mould pit shape structure, heat cure molding is removed in vacuo, demoulding obtains micropin pin arrays, chooses larger-size needle
Shape array mold uses heat cure forming method again, obtains the biggish hole shape PDMS of shape after surface silanization is handled
(dimethyl silicone polymer) mold.The aciculiform mold compared with hollow place PDMS mold and smaller size is selected, utilizes what is reserved when photoetching
Alignment mark, can using heat cure drying and moulding method by the big hole shape permutation of the small pin arrays alignment insertion size of size
Form the micro array structure with regular aciculiform hollow structure.It is filled using materials such as Sodium Hyaluronate, polylactic acid, chitosans,
So that hollow structure outer layer has resolvability.
The production method uses physical alignment mode, can effectively prepare the hollow microneedle arrays with layer structure, utilizes
Different material liquid phase principle, can be filled in the hollow structure of microneedle array liquid and solid and other packing forms it is effective at
Point.
A kind of preparation method of the hollow structure microneedle array with outer layer, specifically comprises the following steps:
(1), two pieces of the work in coordination aciculiform used and hole shape molds, have alignment mark, to guarantee that two pieces of molds can be directed at school
Just, between mold can the different boss of placing height to adjust the depth dimensions of hollow structure prepare the hollow microneedles battle array with outer layer
Column.The implementation of this method is such as conical to common microneedle array mold shape not by the constraint of the mold shape of shape, and four
Pyramid, triangular pyramid, cylindricality etc. have versatility.
It (2) is the silicon dioxide substrate of<100>, two-sided spin coating using crystal orientation for the preparation method of mold in step (1)
5um photoresist after mask, exposure, development, using BOE solution etches window silicon dioxide layer, removes 5um photoresist, with residue
Silicon dioxide layer is exposure mask, can be silicon using 80% KOH solution and cheats, after the completion hot pressing SU-8 dry film, uses litho machine, alignment
Photoetching, it is rear to dry, develop, complete the preparation of original mould.
(3) for outer layer in step (1), it is divided into resolvability in an implementation, solidity can be by additionally applying cutting, swashing
The forms such as the technical solutions apertures such as light punching, grinding.
Purpose of the present invention preparation has the hollow microneedle arrays of outer layer, solves to repeat asking for preparation the type micropin
Topic.
A kind of hollow microneedle arrays production method with outer layer provided by the invention, specifically comprises the following steps:
(1), two pieces of silicon dioxide substrates, crystal orientation<100>, thickness 3um, silicon dioxide layer thickness 300nm, two-sided spin coating are selected
5um positive photoetching rubber, after front baking, mask exposure is rear to dry development；
(2) using surface residual positive photoetching rubber as exposure mask, etching liquid is buffered using BOE, etching silicon dioxide layer is supervised using step instrument
Etching depth is surveyed, until stopping when silicon face, photoresist is removed using acetone, cleans, drying；
(3) KOH solution for preparing mass fraction 80%, maintains 85 degrees Celsius using magnetic heating stirrer, clamps silicon using fixture
Piece tilts 45 °, etches 2h, because the crystal orientation reason etching has self-stopping technology；
(4) after micro- sem observation confirms and obtains the cone hole that apex angle is 54.7 °, SU-8 dry film is selected, using heat-laminator press mold,
Front baking, connects except protective film, determines exposure parameter by thickness using litho machine, rear to dry using mask plate mask exposure, and development is hard
Film；
(5) by original silicon mould silanization, configure PDMS solution by 10:1, by silicon wafer with double-sided adhesive paste in culture dish,
Enter PDMS, pumping bubble 30min, the heat cure 2.5h in 65 DEG C of baking ovens, demoulding obtains two pieces of aciculiform PDMS molds；Size is big
Aciculiform PDMS mould secondary revolving die, obtain hole shape larger size PDMS mold；
(6) using materials such as HA, PVA, PVP, PDMS etc., filling larger size cheats shape PDMS mold respectively, is sought using alignment mark
Alignment point is looked for, and selects proper height boss control back seat thickness degree and outer layer thickness；
(7) bubble is extracted, is kept in 60 ° of baking ovens to drying, is demoulded after taking-up；
(8) by cutting, laser boring and grinding technics, the aperture of needs can be just outputed under this structure.
The above method obtains the hollow microneedle arrays for having outer layer, and outer layer and hollow space size adjustable are whole, and outer layer is according to need
Degradable, solid and hole structure can be prepared as by asking, and meet more scene application needs.The effective of diversified forms can be filled in hollow hole
Ingredient meets the requirement of different application scene to reach.
A kind of hollow microneedle arrays production method with outer layer, specifically comprises the following steps:
(1), using the micropin mold of two pieces of cones (or other Common Shapes), it is directed at and is adjusted height, to prepare band
There are the hollow microneedle arrays of conical outer layer；
(2), it replaces dry film to obtain shape described in the invention using liquid SU-8 glue or other negative photoresists, and is obtained with this
Obtain the hollow microneedle arrays with the shape outer layer；
In conclusion a kind of hollow microneedle arrays production method with outer layer of the invention, since preparation process only passes through pair
On schedule with adjusting height, the hollow structure micropin of dimension adjustable can be prepared on the mold foundation of acquirement.Therefore its system
The features such as standby simple process, low manufacture cost, short preparation period.
Therefore, the invention has the following advantages that the fast development of micromachine, so that the market of micropin becomes wide, it is micro-
Needle is expected to become painless, hygienic syringe substitute.But there is the mechanical property requirements micropin of micropin strength to penetrate skin
Barrier is without being broken, moreover, the reason of outer diameter of micropin has proved to be pain caused by insertion skin.The present invention
There are the hollow microneedle arrays of outer layer, outer layer and hollow space size adjustable are whole, and outer layer can be prepared as degradable, solid according to demand
And hole structure, meet more scene application needs, hollow hole can be filled the effective component of diversified forms and meet different application to reach
The requirement of scene.
The above description is only an embodiment of the present invention, is not intended to limit the scope of the invention, all to utilize this hair
Equivalent structure or equivalent flow shift made by bright description is applied directly or indirectly in other relevant technology necks
Domain is included within the scope of the present invention.
Claims (8)
1. a kind of hollow structure microneedle array production method with outer layer, which is characterized in that including following operating procedure:
S1: original silicon mould is made；
S2: by original silicon mould silanization, configuring PDMS solution by 10:1, by silicon wafer with double-sided adhesive paste in culture dish,
Enter configured PDMS solution, pumping bubble 25-35min；
S3: by the original silicon mould in S2 step, heat cure 1-3h, demoulding obtain two pieces of aciculiforms in 50 DEG C of -70 DEG C of baking ovens
PDMS mold；
S4: by the big aciculiform PDMS mould secondary revolving die of size, hole shape larger size PDMS mold is obtained；
S5: using one of HA, PVA, PVP, PDMS or a variety of, filling larger size cheats shape PDMS mold respectively, uses alignment
Label finds alignment point, and selects proper height boss control back seat thickness degree and outer layer thickness, obtains microneedle array structure；
S6: extracting bubble for the microneedle array structure in S5 step, and keeps in 50 DEG C of -70 DEG C of baking ovens to drying, takes out
After demould；
S7: by cutting, laser boring and grinding technics, aperture is outputed below microneedle array structure.
2. the hollow structure microneedle array production method according to claim 1 with outer layer, which is characterized in that including with
Lower operating procedure:
S1: original silicon mould is made；
S2: by original silicon mould silanization, configuring PDMS solution by 10:1, by silicon wafer with double-sided adhesive paste in culture dish,
Enter configured PDMS solution, pumping bubble 30min；
S3: by the original silicon mould in S2 step, heat cure 2.5h, demoulding obtain two pieces of aciculiform PDMS moulds in 65 DEG C of baking ovens
Tool；
S4: by the big aciculiform PDMS mould secondary revolving die of size, hole shape larger size PDMS mold is obtained；
S5: using one of HA, PVA, PVP, PDMS or a variety of, filling larger size cheats shape PDMS mold respectively, uses alignment
Label finds alignment point, and selects proper height boss control back seat thickness degree and outer layer thickness, obtains microneedle array structure；
S6: extracting bubble for the microneedle array structure in S5 step, and keeps in 60 ° of baking ovens to drying, demoulds after taking-up；
S7: by cutting, laser boring and grinding technics, aperture is outputed below microneedle array structure.
3. the hollow structure microneedle array production method according to claim 1 or 2 with outer layer, which is characterized in that
In step S1, the making step of original silicon mould is as follows:
A: two pieces of the work in coordination aciculiform used and hole shape molds are selected, the hollow microneedle arrays with outer layer are prepared；
B: in a, selecting crystal orientation is the silicon dioxide substrate of<100>, two-sided spin coating 5um photoresist；
C: in b, after silicon dioxide substrate mask, exposure, development, BOE solution etches window silicon dioxide layer, removal are used
5um photoresist；
D: in step c, using silicon dioxide layer surface residual positive photoetching rubber as exposure mask, etching liquid is buffered using BOE, etches dioxy
SiClx layer, after the completion hot pressing SU-8 dry film；
E: using the silicon dioxide layer etching depth in step instrument monitoring S4 step, until stop when silicon face,
F: removing photoresist using acetone, clean, drying；
The aciculiform and hole shape mold have alignment mark, with guarantee two pieces of molds can alignment correction, height can be placed between mold
Spend different boss.
4. the hollow structure microneedle array production method according to claim 3 with outer layer, which is characterized in that described
Microneedle array mold shape is cone, pyramid shape, triangular pyramid or cylindricality.
5. the hollow structure microneedle array production method according to claim 3 with outer layer, which is characterized in that described
BOE buffers etching liquid KOH solution, in step d, prepares the KOH solution of mass fraction 70-90%, uses magnetic heating stirrer
80=90 degrees Celsius are maintained, silicon wafer is clamped using fixture, tilts 30-50 °, etch 1.5-2.5h.
6. the hollow structure microneedle array production method according to claim 3 with outer layer, which is characterized in that described
BOE buffers etching liquid KOH solution, in step d, prepares the KOH solution of mass fraction 80%, is tieed up using magnetic heating stirrer
85 degrees Celsius are held, silicon wafer is clamped using fixture, tilts 45 °, etch 2h.
7. the hollow structure microneedle array production method according to claim 3 with outer layer, which is characterized in that through micro-
After sem observation confirmation obtains the cone hole that apex angle is 54.7 °, SU-8 dry film is selected, using heat-laminator press mold, front baking is connect except protection
Film.
8. the hollow structure microneedle array production method according to claim 3 with outer layer, which is characterized in that use light
Quarter, machine by thickness determined exposure parameter, and used mask plate mask exposure.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910323058.2A CN109893754A (en) | 2019-04-22 | 2019-04-22 | A kind of hollow structure microneedle array production method with outer layer |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910323058.2A CN109893754A (en) | 2019-04-22 | 2019-04-22 | A kind of hollow structure microneedle array production method with outer layer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109893754A true CN109893754A (en) | 2019-06-18 |
Family
ID=66956133
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910323058.2A Pending CN109893754A (en) | 2019-04-22 | 2019-04-22 | A kind of hollow structure microneedle array production method with outer layer |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109893754A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111317911A (en) * | 2020-02-28 | 2020-06-23 | 广东工业大学 | Novel microneedle and manufacturing method thereof |
| CN112618945A (en) * | 2020-12-14 | 2021-04-09 | 北京航空航天大学 | Hollow closed type microneedle, preparation method thereof and operating device comprising microneedle |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1562402A (en) * | 2004-03-31 | 2005-01-12 | 中国科学院理化技术研究所 | Metal micro needles array chip and preparation method, and usage |
| CN101799422A (en) * | 2009-02-10 | 2010-08-11 | 三星电子株式会社 | Microarray reaches the method that obtains the light data from microarray with substrate, microarray method for making |
| US20130096532A1 (en) * | 2011-10-17 | 2013-04-18 | Rutgers, The State University Of New Jersey | Polymer-Based Micro-Needle Array Designs, Fabrication Processes, and Methods of Use Thereof for Drug Delivery |
| CN104057564A (en) * | 2014-06-06 | 2014-09-24 | 游学秋 | Micro-needle making method based on inclined casting mould |
| CN104117137A (en) * | 2014-07-08 | 2014-10-29 | 清华大学 | Capsule type hollow medicine loading micro-needle array and producing method thereof |
| CN106730309A (en) * | 2016-12-19 | 2017-05-31 | 山东元旭光电股份有限公司 | A kind of silicon micropin substrate and preparation method thereof |
| US20170246440A1 (en) * | 2016-02-29 | 2017-08-31 | EP Technologies LLC | Apparatuses and methods for plasmaporation using microneedles |
-
2019
- 2019-04-22 CN CN201910323058.2A patent/CN109893754A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1562402A (en) * | 2004-03-31 | 2005-01-12 | 中国科学院理化技术研究所 | Metal micro needles array chip and preparation method, and usage |
| CN101799422A (en) * | 2009-02-10 | 2010-08-11 | 三星电子株式会社 | Microarray reaches the method that obtains the light data from microarray with substrate, microarray method for making |
| US20130096532A1 (en) * | 2011-10-17 | 2013-04-18 | Rutgers, The State University Of New Jersey | Polymer-Based Micro-Needle Array Designs, Fabrication Processes, and Methods of Use Thereof for Drug Delivery |
| CN104057564A (en) * | 2014-06-06 | 2014-09-24 | 游学秋 | Micro-needle making method based on inclined casting mould |
| CN104117137A (en) * | 2014-07-08 | 2014-10-29 | 清华大学 | Capsule type hollow medicine loading micro-needle array and producing method thereof |
| US20170246440A1 (en) * | 2016-02-29 | 2017-08-31 | EP Technologies LLC | Apparatuses and methods for plasmaporation using microneedles |
| CN106730309A (en) * | 2016-12-19 | 2017-05-31 | 山东元旭光电股份有限公司 | A kind of silicon micropin substrate and preparation method thereof |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111317911A (en) * | 2020-02-28 | 2020-06-23 | 广东工业大学 | Novel microneedle and manufacturing method thereof |
| CN112618945A (en) * | 2020-12-14 | 2021-04-09 | 北京航空航天大学 | Hollow closed type microneedle, preparation method thereof and operating device comprising microneedle |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104780966B (en) | The manufacture method of molded product and percutaneous absorbtion piece | |
| JP6600689B2 (en) | Pattern sheet manufacturing method | |
| CN103568160B (en) | A kind of preparation method of polymer material micro-needle array patch | |
| KR102074603B1 (en) | Manufacturing method of mold, manufacturing method of pattern sheet, manufacturing method of electroforming mold, and manufacturing method of mold using electroforming mold | |
| US10814118B2 (en) | Transdermal absorption sheet | |
| CN109893754A (en) | A kind of hollow structure microneedle array production method with outer layer | |
| Mishra et al. | Development of SU-8 hollow microneedles on a silicon substrate with microfluidic interconnects for transdermal drug delivery | |
| CN103889499B (en) | The manufacture method of hollow spicule and hollow spicule | |
| JP2011083387A (en) | Method of manufacturing needle-shaped body, needle-shaped body and needle-shaped body holding sheet | |
| US10195768B2 (en) | Method of manufacturing mold and method of manufacturing pattern sheet | |
| JP2009082206A (en) | Method of manufacturing functional film | |
| JP2009241357A (en) | Method for producing functional sheet | |
| JP2011245055A (en) | Method for manufacturing needle sheet | |
| EP3153291B1 (en) | Method of manufacturing mold and method of manufacturing pattern sheet | |
| CN109278219A (en) | A kind of microneedles template and the preparation method and application thereof | |
| US10870223B2 (en) | Method of manufacturing needle-like array sheet | |
| Yan et al. | Hollow metallic microneedles fabricated by combining bulk silicon micromachining and UV–LIGA technology | |
| JP2009083125A (en) | Method and apparatus for producing functional film | |
| JP6432316B2 (en) | Manufacturing method of needle-shaped body | |
| JP2017213171A (en) | Recessed pattern mold, method of manufacturing recessed pattern mold, and method of manufacturing pattern sheet | |
| Larrañeta et al. | Microneedle manufacturing and testing | |
| CA3111688A1 (en) | Hollow microneedle for transdermal delivery of active molecules and/or for the sampling of biological fluids and manufacturing method of such hollow microneedle | |
| JP2018042677A (en) | Concave pattern mold and manufacturing method of pattern sheet | |
| CN114225210A (en) | Novel transdermal drug delivery micro-nano structure and preparation method thereof | |
| JP2015208922A (en) | Method for producing acicular body |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| AD01 | Patent right deemed abandoned | ||
| AD01 | Patent right deemed abandoned |
Effective date of abandoning: 20220114 |