CN104307097B - A kind of manufacture method of flexible substrates metal micro-needle array - Google Patents
A kind of manufacture method of flexible substrates metal micro-needle array Download PDFInfo
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- CN104307097B CN104307097B CN201410585413.0A CN201410585413A CN104307097B CN 104307097 B CN104307097 B CN 104307097B CN 201410585413 A CN201410585413 A CN 201410585413A CN 104307097 B CN104307097 B CN 104307097B
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- flexible substrates
- array
- needle
- solidifiable
- metal micro
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
-
- 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
- A61M2037/0023—Drug applicators 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
- A61M2037/0053—Methods for producing microneedles
Abstract
The present invention relates to a kind of technical field of biomedical engineering method, more particularly, to a kind of manufacture method of flexible substrates metal micro-needle array.The making of flexible substrates metal micro-needle array includes that a. makes solidifiable ferromagnetic fluids；B. flexible substrates are prepared；C., the drop of solidifiable ferromagnetic fluids is arranged the assembly for forming solidifiable ferromagnetic fluids droplet array and flexible substrates on a flexible substrate in array-like；D. " assemblys of solidifiable ferromagnetic fluids droplet array and flexible substrates " that obtain in step c are placed in magnetic field, make each drop be changing into needle-like, then solidify which, form the microneedle array structure of stable, solidification；E. in the one layer of homogeneous metal of microneedle array body structure surface vacuum splashing and plating obtained by step d, form metal micro-needle array.Microneedle array structure is formed by ferromagnetic fluids droplet interaction of the magnetic field with the ferromagnetic particle of level containing magnetic Nano.
Description
Technical field
The present invention relates to the technical field of biomedical engineering method, micro- more particularly, to a kind of flexible substrates metal
The manufacture method of pin array.
Background technology
The improvement of administering mode is a basic and important problem in medical field.
Its traditional approach mainly has oral and injection.Although the former is convenient and easy, as the interference of digestive system is caused
The inefficiency of medicine；Though and the oral curative effect shortcoming that the latter avoids, often can bring more pain to patient.Additionally,
It is above-mentioned that both wait to improve at the aspect of medicament slow release.
Currently, emerging administering mode mainly has transdermal administration and drug administration by injection.The former relies on the infiltration of pharmaceutical through skin
To carry out medicine transmission, due to the obstruction of skin, efficiency is still relatively low；And a kind of the latter's minimally invasive means then for relative efficiency,
Had concurrently efficiency high, damage it is low, can the three advantages such as slow release.Although micropin medicine-feeding technology has many advantages, such as, good
The making of micropin is but a great problem.The characteristics of having scaled fine small due to micropin, with traditional handicraft processing micropin very
It is difficult.
Early stage micropin is mainly silicon materials, is currently being difficult to promote because easy brittle failure and biocompatibility fail to understand.And be polymerized
Thing micropin is good in the above performance but is difficult to.Relatively, metal micro-needle is showed in mechanical performance well, some conjunctions
The biocompatibility of gold is good, processed technology maturation, it is adaptable to which micropin is produced.
Based on MEMS（MEMS technology）LIGA technologies provide effective way for the processing of metal micro-needle array.
But due to synchronous X-ray costly and fabrication cycle is long, the cost of LIGA fabrication techniques micropins is very high, and process is complicated not
Easy to control, metal working process limits the exploitation of metal micro-needle and promotes.
The content of the invention
It is an object of the invention to overcome the deficiencies in the prior art, there is provided a kind of making of flexible substrates metal micro-needle array
Method, which is simple to operate, and fabrication cycle is short.
To solve above-mentioned technical problem, the technical solution used in the present invention is：
A kind of manufacture method of flexible substrates metal micro-needle array, the flexible substrates metal micro-needle array include flexible base
Bottom 1, microneedle array 2, wherein microneedle array 2 are fixed in flexible substrates 1；
The manufacture method of the flexible substrates metal micro-needle array comprises the following steps：
A. solidifiable ferromagnetic fluids are made；
B. flexible substrates 1 are prepared；
C. the drop of solidifiable ferromagnetic fluids is arranged in flexible substrates 1 in array-like, forms solidifiable ferromagnetic
Property fluid drop array and flexible substrates assembly 7；
D. the assembly 7 by the solidifiable ferromagnetic fluids droplet array obtained in step c with flexible substrates is placed in magnetic field
In, make each drop be changing into needle-like, then solidify which, form the microneedle array structure of stable, solidification；
E. in the microneedle array body structure surface vacuum splashing and plating layer of metal obtained by step d, form flexible substrates metal micro-needle
Array.
The manufacture method of flexible substrates metal micro-needle array of the present invention, by the action of a magnetic field in arranging on a flexible substrate
Solidifiable ferromagnetic fluids droplet array, makes drop that the needle-like in point in bottom width is deformed under magneticaction, treats its solidification
Afterwards in microneedle array body structure surface vacuum splashing and plating layer of metal, metal micro-needle array structure is formed, the manufacture method is simple, be easy to
Operation, make efficiency is high can effectively to reduce production cost simultaneously.The complicated technical process of MEMS technology can be avoided, is facilitated implementation and is criticized
Amount is produced, and economic benefit and social benefit are notable.
As the further improvement of the manufacture method of above-mentioned flexible substrates metal micro-needle array of the invention, to make solidifiable ferrum
Magnetic flow has preferable magnetic and mobility and is easy to solidification, and the solidifiable ferromagnetic fluids include：Magnetic Nano is micro-
Rice grain, macromolecular material and firming agent.
As the further improvement of the manufacture method of above-mentioned flexible substrates metal micro-needle array of the invention, to make flexible substrates
With enough flexibilities, the material of the flexible substrates is preferably macromolecular material, such as：PDMS, rubber, epoxy resin, silica gel,
One or more combination in terylene and cotton etc..
It is as the further improvement of the manufacture method of above-mentioned flexible substrates metal micro-needle array of the invention, described " to coagulate
Gu the drop of ferromagnetic fluids is arranged in flexible substrates 1 in array-like ground " method can be arbitrary in several ways
Kind：The 1st, casement 5 is close to be placed on the upper surface of flexible substrates 1, then in the upper surface brushing solidifiable ferromagnetism stream of casement 5
Body, then removes casement 5 and unnecessary solidifiable ferromagnetic fluids thereon, leaves droplet array in the upper surface of flexible substrates 1；
2nd, solidifiable ferromagnetic fluids are loaded in the cavity of casement 5 and piston and barrel composition, being caused by piston applying pressure can
Solidification ferromagnetic fluids are flowed out from the aperture of casement 5, and are attached in flexible substrates 1 and are formed droplet array；3rd, adopt hollow needle
Mould 6, forms droplet array in the way of outpouring to flexible substrates 1；4th, using solid needle mould 6, dipped with solid needle mould 6 appropriate
Solidifiable ferromagnetic fluids simultaneously attach it to generate droplet array in flexible substrates 1.Above-mentioned several method can it is convenient, fast,
The droplet array of solidifiable ferromagnetic fluids is formed accurately.
As the further improvement of the manufacture method of above-mentioned flexible substrates metal micro-needle array of the invention, to make magnetic fluid
The solidification of granule is uniform, quick, stable, and curing mode is preferably：Using be heating and curing or light irradiation solidification.
As the further improvement of the manufacture method of above-mentioned flexible substrates metal micro-needle array of the invention, it is heating and curing and can adopts
Heating film 4 is set used in 1 bottom of flexible substrates, is heating and curing using heating film 4.By mixing to substrate to heating film 4
Thing solution is heated, and is accelerated epoxy resin cure, that is, is accelerated the solidification of microneedle array structure.Further, it is to improve electric heating to turn
Efficiency high is changed, increased the service life, improved fatigue durability and avoid magnetic field from being affected, heating film 4 can select carbon fiber to add
Hotting mask.
Description of the drawings
Fig. 1 is " casement " thin-slab structure schematic diagram.
Fig. 2 is " needle mould " overall structure diagram.
Fig. 3 is " assemblys of solidifiable ferromagnetic fluids droplet array and flexible substrates " schematic diagram.
Fig. 4 is the structural representation of the microneedle array making apparatus based on the magnetic fluid drop in flexible substrates.
Fig. 5 is the model of action schematic diagram of " casement " to flexible substrates.
Fig. 6 is the model of action schematic diagram of " needle mould " to flexible substrates.
Fig. 7 is " extrusion type casement " schematic configuration diagram.
Specific embodiment
With reference to specific embodiment, the present invention is further illustrated.Wherein, being for illustration only property of accompanying drawing explanation,
What is represented is only schematic diagram, rather than pictorial diagram, it is impossible to be interpreted as the restriction to this patent；In order to the reality of the present invention is better described
Apply example, accompanying drawing some parts have omission, zoom in or out, and do not represent the size of actual product；To those skilled in the art
For, some known features and its explanation in accompanying drawing may be omitted and be will be understood by.
The corresponding same or analogous part of same or analogous label in the accompanying drawing of the embodiment of the present invention；In retouching for the present invention
In stating, it is to be understood that if having term " on ", D score, the orientation of the instruction such as "left", "right" or position relationship be based on accompanying drawing
Shown orientation or position relationship, are for only for ease of the description present invention and simplify description, rather than indicate or imply indication
Device or element must have specific orientation, with specific azimuth configuration and operation, therefore position relationship described in accompanying drawing
Term being for illustration only property explanation, it is impossible to be interpreted as the restriction to this patent, for the ordinary skill in the art, can
To understand the concrete meaning of above-mentioned term as the case may be.
Embodiment one：
A kind of manufacture method of flexible substrates metal micro-needle array, the flexible substrates metal micro-needle array include flexible base
Bottom 1, microneedle array 2, wherein microneedle array 2 are fixed in flexible substrates 1；
The manufacture method of the flexible substrates metal micro-needle array comprises the following steps：
A. " solidifiable ferromagnetic fluids " are made：The solidifiable ferromagnetic fluids include magnetic Nano or micron particle,
Macromolecular material and firming agent, according to performance requirement, mix according to suitable ratio.The present embodiment selects magnetic Nano
Grain, and epoxy resin is selected as macromolecular material, select epoxy curing agent as firming agent, its ratio is：Magnetic is received
Rice grain：Epoxy resin：Epoxy curing agent=5:3:2；
B. according to predetermined design, soft solid matter is fabricated to into laminar flexible substrates 1, for carrying micropin battle array
Row, its material have various available selections, generally macromolecular material, such as PDMS, epoxy resin, rubber, silica gel, terylene and cotton
In one or more of combination etc., which makes, moulding process for respective material usual technique, the present embodiment selected with silica gel
As the material for making flexible substrates 1；
C. the assembly 7 of solidifiable ferromagnetic fluids droplet array and flexible substrates is made, casement 5 is closely covered and is placed on
The upper surface of flexible substrates 1, constitutes the combination as shown in " Fig. 5 ", wherein, then the roomy surface horizontal positioned of casement 5 may be used
Solidification ferromagnetic fluids are equably painted on above pore membrane 5, until aperture fully, is equably full of by liquid.Then, edge
Vertical direction（Parallel and direction in contrast to gravity）Casement is separated from the upper surface of flexible substrates 1, then in the hole in casement 5
Some is stayed on the upper surface of flexible substrates 1 by liquid, will constitute solidifiable ferromagnetic fluids drop as shown in the figure 3
The assembly 7 of array and flexible substrates；
D. aciculiform is produced：Assembly 7 of the above-mentioned solidifiable ferromagnetic fluids droplet array with flexible substrates is inserted into magnetic field
Generating meanss 3（The border schematic diagram of the upper limit end face edge of cylindrical magnetic field areas of the device 3 by utilizing, does not represent real
The structure of border equipment）Magnetic field in certain hour, magnetic field intensity is about 0.4T, and the drop on the assembly 7 will be subject to magnetic field
Effect becomes needle-like（The shape of point in bottom width）, as shown in 2 in " Fig. 4 ".Then solidify：Start advance place mat soft in magnetic field
Property substrate 1 below carbon fiber heating film 4, make liquid needle-like array applicator solidify, heating-up temperature be 90-130 degree Celsius between.
（In the case of using other conditions of cure, heating film 4 also can be replaced other equipment, such as using light（Infrared light）Gu
In the case of change, change is used into light source-providing device.）After 4-5 hours, microneedle array solidification is completed, and obtains micropin battle array
Array structure；
E. in the microneedle array body structure surface vacuum splashing and plating layer of metal obtained by step d, form metal micro-needle array.
Embodiment two：
The present embodiment is similar with embodiment one, and institute's difference is, in the present embodiment " by solidifiable ferromagnetic fluids
Drop in array-like be arranged in flexible substrates 1 " method be：Solidifiable ferromagnetic fluids are loaded into casement 5 and piston
And in the cavity of barrel composition, pressure is applied by piston solidifiable ferromagnetic fluids are flowed out from the aperture of casement 5, and it is attached
Droplet array is formed in flexible substrates 1.
Embodiment three：
The present embodiment is similar with embodiment one, and institute's difference is, in the present embodiment " by solidifiable ferromagnetic fluids
Drop in array-like be arranged in flexible substrates 1 " method be：Using hollow needle mould 6, with what is outpoured to flexible substrates 1
Mode forms droplet array.
Example IV：
The present embodiment is similar with embodiment one, and institute's difference is, in the present embodiment " by solidifiable ferromagnetic fluids
Drop in array-like be arranged in flexible substrates 1 " method be：Using solid needle mould 6, dipped in right amount with solid needle mould 6
Solidifiable ferromagnetic fluids and attach it to generate droplet array in flexible substrates 1.
Obviously, the above embodiment of the present invention is only intended to clearly illustrate example of the present invention, and is not right
The restriction of embodiments of the present invention.For those of ordinary skill in the field, may be used also on the basis of the above description
To make other changes in different forms.There is no need to be exhaustive to all of embodiment.It is all this
Any modification, equivalent and improvement made within the spirit and principle of invention etc., should be included in the claims in the present invention
Protection domain within.
Claims (10)
1. a kind of manufacture method of flexible substrates metal micro-needle array, the flexible substrates metal micro-needle array include flexible substrates
（1）, microneedle array（2）, wherein microneedle array（2）It is fixed on flexible substrates（1）On；
Characterized in that, the manufacture method of the flexible substrates metal micro-needle array comprises the following steps：
A. solidifiable ferromagnetic fluids are made；
B. flexible substrates are prepared（1）；
C. the drop of solidifiable ferromagnetic fluids is arranged in into flexible substrates in array-like（1）On, form solidifiable ferromagnetism
The assembly of fluid drop array and flexible substrates（7）；
D. by the solidifiable ferromagnetic fluids droplet array obtained in step c and the assembly of flexible substrates（7）It is placed in magnetic field,
Make each drop be changing into needle-like, then solidify which, form the microneedle array structure of stable, solidification；
E. in the microneedle array body structure surface vacuum splashing and plating layer of metal obtained by step d, form flexible substrates metal micro-needle array.
2. the manufacture method of flexible substrates metal micro-needle array according to claim 1, it is characterised in that the solidifiable
Ferromagnetic fluids include：Magnetic Nano or micron particle, macromolecular material and firming agent.
3. the manufacture method of flexible substrates metal micro-needle array according to claim 1, it is characterised in that the flexible base
The material at bottom is the combination of one or more in PDMS, rubber, epoxy resin, terylene and cotton.
4. the manufacture method of flexible substrates metal micro-needle array according to claim 1, it is characterised in that it is described " can
The drop of solidification ferromagnetic fluids is arranged in flexible substrates in array-like（1）On " method be：By casement（5）It is close to place
In flexible substrates（1）Upper surface, then in casement（5）Upper surface brushing solidifiable ferromagnetic fluids, remove casement afterwards
（5）And unnecessary solidifiable ferromagnetic fluids thereon, in flexible substrates（1）Upper surface leave droplet array.
5. the manufacture method of flexible substrates metal micro-needle array according to claim 1, it is characterised in that it is described " can
The drop of solidification ferromagnetic fluids is arranged in flexible substrates in array-like（1）On " method be：By solidifiable ferromagnetic fluids
Load casement（5）In the cavity constituted with piston and barrel, pressure is applied by piston and solidifiable ferromagnetic fluids is caused from hole
Mould（5）Aperture flow out, and be attached to flexible substrates（1）Upper formation droplet array.
6. the manufacture method of flexible substrates metal micro-needle array according to claim 1, it is characterised in that it is described " can
The drop of solidification ferromagnetic fluids is arranged in flexible substrates in array-like（1）On " method be：Using hollow needle mould（6）, with
To flexible substrates（1）The mode for outpouring forms droplet array.
7. the manufacture method of flexible substrates metal micro-needle array according to claim 1, it is characterised in that it is described " can
The drop of solidification ferromagnetic fluids is arranged in flexible substrates in array-like（1）On " method be：Using solid needle mould（6）, with
Solid needle mould（6）Dip appropriate solidifiable ferromagnetic fluids and attach it to flexible substrates（1）Upper generation droplet array.
8. the manufacture method of flexible substrates metal micro-needle array according to claim 1, it is characterised in that step d
In be cured as：Using be heating and curing or light irradiation solidification.
9. the manufacture method of flexible substrates metal micro-needle array according to claim 8, it is characterised in that the heating is solid
Turn to：In flexible substrates（1）Bottom arranges heating film（4）, using heating film（4）It is heating and curing.
10. the manufacture method of flexible substrates metal micro-needle array according to claim 9, it is characterised in that the heating
Film（4）For carbon fiber heating film.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104707240B (en) * | 2015-03-06 | 2017-09-22 | 中山大学 | The preparation method that magnetic guides the connected porous microneedle array of nanometer |
| CN105169552B (en) * | 2015-08-25 | 2019-01-04 | 中山大学 | The production method for the metal-polymer microneedle array that magnetic field stretches |
| CN105498081A (en) * | 2015-09-04 | 2016-04-20 | 李媚 | Sterile microstructure body and preparation method thereof |
| WO2017177971A1 (en) * | 2016-04-14 | 2017-10-19 | 中国科学院苏州纳米技术与纳米仿生研究所 | Magnetic microchip having graphic coding, preparation method therefor, and applications thereof |
| CN106983507A (en) * | 2017-02-21 | 2017-07-28 | 中山大学 | A kind of flexible microelectrode arrays measured for body electrical signals and preparation method |
| CN110811598A (en) * | 2019-11-14 | 2020-02-21 | 深圳先进技术研究院 | Wrist strap type biological signal acquisition equipment and manufacturing method thereof |
| CN115646562B (en) * | 2022-09-27 | 2023-08-11 | 郑州大学 | Micro-magnetic effect-based control chip, detection assembly, detection system and method |
| CN115684580B (en) * | 2022-09-27 | 2023-08-25 | 郑州大学 | Microsphere array chip based on magnetic control, detection assembly, detection system and method |
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