CN109141570A - A kind of temperature control type flexible capacitive sensor and preparation method for drug release - Google Patents
A kind of temperature control type flexible capacitive sensor and preparation method for drug release Download PDFInfo
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- CN109141570A CN109141570A CN201811092026.8A CN201811092026A CN109141570A CN 109141570 A CN109141570 A CN 109141570A CN 201811092026 A CN201811092026 A CN 201811092026A CN 109141570 A CN109141570 A CN 109141570A
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- 229940079593 drug Drugs 0.000 title claims abstract description 66
- 230000009975 flexible effect Effects 0.000 title claims abstract description 51
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- 239000010409 thin film Substances 0.000 claims abstract description 41
- 239000000017 hydrogel Substances 0.000 claims abstract description 39
- 108010022355 Fibroins Proteins 0.000 claims abstract description 34
- 239000010408 film Substances 0.000 claims abstract description 33
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 31
- 229910021389 graphene Inorganic materials 0.000 claims abstract description 31
- 239000000758 substrate Substances 0.000 claims abstract description 23
- QNILTEGFHQSKFF-UHFFFAOYSA-N n-propan-2-ylprop-2-enamide Chemical compound CC(C)NC(=O)C=C QNILTEGFHQSKFF-UHFFFAOYSA-N 0.000 claims abstract description 16
- 238000000034 method Methods 0.000 claims description 9
- 239000000463 material Substances 0.000 claims description 6
- 239000004205 dimethyl polysiloxane Substances 0.000 claims description 5
- 235000013870 dimethyl polysiloxane Nutrition 0.000 claims description 5
- CXQXSVUQTKDNFP-UHFFFAOYSA-N octamethyltrisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)O[Si](C)(C)C CXQXSVUQTKDNFP-UHFFFAOYSA-N 0.000 claims description 5
- 238000004987 plasma desorption mass spectroscopy Methods 0.000 claims description 5
- 238000001020 plasma etching Methods 0.000 claims description 5
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 claims description 5
- -1 graphite Alkene Chemical class 0.000 claims description 4
- 239000011248 coating agent Substances 0.000 claims description 3
- 238000000576 coating method Methods 0.000 claims description 3
- 238000005553 drilling Methods 0.000 claims description 3
- 238000005266 casting Methods 0.000 claims description 2
- 238000010276 construction Methods 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000005611 electricity Effects 0.000 claims 1
- 239000000499 gel Substances 0.000 claims 1
- 229910002804 graphite Inorganic materials 0.000 claims 1
- 239000010439 graphite Substances 0.000 claims 1
- 239000003990 capacitor Substances 0.000 abstract 2
- 238000005229 chemical vapour deposition Methods 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 238000011160 research Methods 0.000 description 4
- 230000008961 swelling Effects 0.000 description 4
- 238000009792 diffusion process Methods 0.000 description 3
- 238000012377 drug delivery Methods 0.000 description 3
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- 230000008602 contraction Effects 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 229910010272 inorganic material Inorganic materials 0.000 description 2
- 239000011147 inorganic material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 238000004377 microelectronic Methods 0.000 description 2
- 229920003213 poly(N-isopropyl acrylamide) Polymers 0.000 description 2
- 229920003207 poly(ethylene-2,6-naphthalate) Polymers 0.000 description 2
- 239000011112 polyethylene naphthalate Substances 0.000 description 2
- 229920000139 polyethylene terephthalate Polymers 0.000 description 2
- 239000005020 polyethylene terephthalate Substances 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- 239000004642 Polyimide Substances 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000002390 adhesive tape Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
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- 238000011161 development Methods 0.000 description 1
- 238000011982 device technology Methods 0.000 description 1
- 125000004386 diacrylate group Chemical group 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 108010025899 gelatin film Proteins 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 230000010355 oscillation Effects 0.000 description 1
- 238000000059 patterning Methods 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 230000007096 poisonous effect Effects 0.000 description 1
- 229920001721 polyimide Polymers 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 229920005573 silicon-containing polymer Polymers 0.000 description 1
- 238000009450 smart packaging Methods 0.000 description 1
- 238000004528 spin coating Methods 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
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Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01F—MEASURING VOLUME, VOLUME FLOW, MASS FLOW OR LIQUID LEVEL; METERING BY VOLUME
- G01F22/00—Methods or apparatus for measuring volume of fluids or fluent solid material, not otherwise provided for
Landscapes
- Physics & Mathematics (AREA)
- Fluid Mechanics (AREA)
- General Physics & Mathematics (AREA)
- Medicinal Preparation (AREA)
Abstract
A kind of temperature control type flexible capacitive sensor and preparation method for drug release, the capacitance sensor include the first pole plate, the second pole plate and temperature control type drug release hydrogel thin film positioned there between；First pole plate and the second pole plate includes: flexible substrates, the fibroin albumen film layer in the flexible substrates and the Graphene electrodes layer in the fibroin albumen film layer；The temperature control type drug release hydrogel thin film is the temperature sensitive film of poly-N-isopropyl acrylamide.The present invention provides a kind of temperature control type flexible capacitive sensor for drug release, when variation of ambient temperature, drug release is adjusted using the contractility of temperature control type drug release hydrogel thin film, and then capacitor the two poles of the earth plate spacing changes, is presented as that capacitor changes.
Description
Technical field
The present invention relates to temperature control type drug delivery technologies fields, and in particular to a kind of temperature control type for drug release is flexible
Capacitance sensor and preparation method thereof.
Background technique
In dosing system, optimal administration mode is drug fixed point, timing, quantitative release, to remain normal
Blood concentration, do not cause drug accumulation to be poisoned, while reducing poisonous side effect of medicine.Biosensor based on MEMS technology and
Microfluidic system is largely paid close attention to, and strong tool is provided for the research and exploration of life science, in biomedicine
It is used widely in the fields such as engineering.Currently, the sensor majority for drug release is integrated in single core using MEMS technology
Piece, but MEMS integrated device technology is complex, at high cost, environmental pollution is serious.Had in more than 10 years of past to solution
The research and development of machine and inorganic material, especially hydrogel have expedited the emergence of the application study of various flexible intelligent devices.Solution has
Machine and inorganic material making devices are different from microelectronic, and maximum feature is that any material is deposited in a manner of increasing material manufacturing
On, prepare the flexible device of large area, flexibility, low cost.Flexible sensor structure type is versatile and flexible, can be according to measurement item
The requirement of part is arbitrarily arranged, easily can carry out accurate quick measurement, these novel flexibles to particular surroundings and signal
Sensor plays an important role in biological medicine, electronic skin, wearable electronic product and intelligent packaging field.Using temperature control type medicine
Object discharges sensitive membrane of the hydrogel thin film as sensor, and release amount of medicine is restricted by temperature, and release is in temperature oscillation
Existing " faster slower " response characteristic.When 32 DEG C of temperature <, poly-N-isopropyl acrylamide hydrogel thin film is in the state of swelling,
Drug molecule dissolves diffusion rate very little in a solvent.When 32 DEG C of temperature >, poly-N-isopropyl acrylamide hydrogel thin film
Sudden contraction, moisture and drug inside hydrogel discharge outward.Expanded using temperature-sensitive hydrogel film with temperature and
It shrinks and then causes the principle of volume change to make and become spacing type capacitance sensor as worldwide research hotspot.It is also
Biomedical microelectronics research field realizes that drug effectively controls and the important channel discharged and research hotspot.
Summary of the invention
Present invention aim to address in the existing biosensor based on MEMS technology and micro-fluidic drug delivery system
Existing subproblem provides a kind of temperature control type flexible capacitive sensor and preparation method thereof for drug release.
The purpose of the present invention is what is be achieved through the following technical solutions:
A kind of temperature control type flexible capacitive sensor for drug release, including the first pole plate, the second pole plate and be located at two
Temperature control type drug release hydrogel thin film between person；First pole plate and the second pole plate include: flexible substrates, described soft
The Graphene electrodes layer in fibroin albumen film layer and the fibroin albumen film layer in property substrate；The temperature control type drug
Release hydrogel thin film is the temperature sensitive film of poly-N-isopropyl acrylamide.
Preferably, the material of the flexible substrates be PET (polyethylene terephthalate), PI (polyimides),
One of PVA (polyvinyl alcohol) and PEN (polyethylene naphthalate)；The fibroin albumen on the flexible substrates surface is thin
Film layer is as insulating layer.
Preferably, the flexible substrates surface is coated with the fibroin albumen film layer of one layer of 30nm-100nm thickness, then by it
It immerses in the silk fibroin solution of concentration 3%-8% (quality), taking out can be in flexible substrates surface system after being dried with 70 DEG C -200 DEG C
Obtain fibroin albumen film layer.
Preferably, the fibroin albumen thin film layer thickness being located in flexible substrates is 200nm-600nm, the stone
Black alkene electrode layer with a thickness of 50nm-150nm.
Preferably, the Graphene electrodes layer is that CVD graphene is first transferred to fibroin albumen thin-film surface, then
It is formed using reactive ion etching graphene pattern.
Preferably, first pole plate has 10 μm -100 μm of aperture.
Preferably, the temperature control type drug release hydrogel thin film is the poly-N-isopropyl third with a thickness of 5 μm -200 μm
The temperature sensitive film of acrylamide.
Preferably, the temperature sensitive film of the poly-N-isopropyl acrylamide, when 32 DEG C of temperature <, poly-N-isopropyl propylene
Amide hydrogel thin film is in solvent swelling state, and drug molecule diffusion rate very little is still in solvent.When 32 DEG C of temperature >,
Poly-N-isopropyl acrylamide hydrogel thin film is acutely shunk, and the moisture and drug inside hydrogel discharge outward.
Preferably, the temperature control type drug release hydrogel thin film is formed in the Graphene electrodes layer table of the second pole plate
Face.
Preferably, the stacking knot that first pole plate, temperature control type drug release hydrogel thin film and the second pole plate are formed
The side of structure is encapsulated using PDMS.
Another aspect of the invention is the preparation methods of the temperature control type flexible capacitive sensor for drug release, including such as
Lower step:
(1) the first pole plate and the second pole plate are prepared: preparing fibroin albumen film layer as insulating layer on flexible substrates surface,
CVD (chemical vapor deposition) graphene is transferred to fibroin albumen thin-film surface, then utilizes reactive ion etching graphene
Patterning obtains Graphene electrodes layer；10 μm -100 μm of aperture is bored on first pole plate using laser drilling processes to use
In drug release；
(2) the Graphene electrodes layer surface coating poly-N-isopropyl acrylamide using the method for coating in the second pole plate is cast
Film liquid forms temperature control type drug release hydrogel thin film；
(3) stacking of the first pole plate is set on the temperature control type drug release hydrogel thin film.
It is 200nm-600nm that the step (1), which is located at the fibroin albumen thin film layer thickness in flexible substrates,；The graphene
Electrode layer with a thickness of 50nm-250nm.
Preferably, the temperature control type drug release hydrogel thin film of the step (2) is with a thickness of 5 μm -200 μm.
Preferably, using PDMS (dimethyl silicone polymer) to first pole plate, temperature control type drug release hydrogel
The side for the stepped construction that film is formed with the second pole plate is packaged.
Beneficial effects of the present invention: the present invention provides a kind of temperature control type flexible capacitive sensor for drug release and
Preparation method can expand drug delivery system and vitro drug release behavior constructing plan.Fibroin albumen is as a kind of day
Right high molecular material has many advantages, such as excellent mechanical performance, excellent translucency, degradable, good biocompatibility, meets state
Family's strategy of sustainable development.Meanwhile the present invention mutually ties graphene, fibroin albumen in the application of biological field and sensory field
It closes, for developing new nuisanceless, fixed point, timing, dosing system have important practical significance.This is for drug release
Temperature control type flexible capacitive sensor principle is simple, flexible, biological safety is good, it is inexpensive, prepare material therefor rich reserves
And it is environmental-friendly, and make using simple instrument and equipment and conventional process flow and realize, have using of the invention
Promotion and application.
Detailed description of the invention
Fig. 1 is the structural schematic diagram obtained by embodiment 1 for the temperature control type flexible capacitive sensor of drug release.
Wherein, 1 is flexible substrates；2 be fibroin albumen film layer；3 be Graphene electrodes layer；4 be temperature control type drug release
Hydrogel thin film.
Specific embodiment
In order to better illustrate the present invention, with reference to the attached drawing in the embodiment of the present invention, in the embodiment of the present invention
Technical solution is further discussed in detail.
Embodiment 1
For the structure of the temperature control type flexible capacitive sensor of drug release as shown in Figure 1, including the obtained by the embodiment
One pole plate (such as in figure temperature control type drug release hydrogel thin film 4 top), the second pole plate (such as temperature control type drug release in figure
4 lower section of hydrogel thin film) and positioned at temperature control type drug release hydrogel thin film 4 between the two；First pole plate and the second pole plate
It can have identical layer structure, can specifically include: flexible substrates 1, fibroin albumen film layer 2 and Graphene electrodes layer 3；
Wherein, fibroin albumen film layer 2 is located in flexible substrates 1；The fibroin of flexible substrates 1 surface spin coating, one layer of 50nm thickness
Albumen film layer is then immersed in the silk fibroin solution of concentration 5% (quality), and taking out can be in flexible substrates after being dried with 75 DEG C
The fibroin albumen film layer 2 that a layer thickness is about 450nm is prepared in 1 surface, and fibroin albumen film layer 2 is used as insulating layer；
Graphene is prepared using CVD method, graphene prepared by CVD method is transferred to using heat release adhesive tape by above-mentioned fibroin egg
The graphene on 2 surface of fibroin albumen film layer is patterned to obtain by 2 surface of white film layer using reactive ion etching technology
Graphene electrodes layer 3, to obtain pole plate, wherein bore 10 μm -100 μm small on the first pole plate using laser drilling processes
Hole is used for drug release；
PVDF-g- is prepared into n-isopropyl acrylamide monomer, alkali process PVDF powder, azodiisobutyronitrile reaction
PNIPAAm lopping copolymer reacts 1 hour at 80 DEG C.The PVDF-g-PNIPAAm lopping copolymer of 15g is taken to be dissolved in 32ml DMF
It is reacted 3 hours for 60 DEG C in solvent, prepares poly-N-isopropyl acrylamide casting solution after deaeration is sufficiently stirred.0.5g is added simultaneously
Diacrylate -1,6- hexylene glycol ester for make in the drying process remain azodiisobutyronitrile carry out heat cross-linking, improve film
Intensity avoid simultaneously temperature control type drug release hydrogel thin film in swelling process repeatedly with graphene fibroin albumen membrane electrode
Layer is not combined closely.
It is coated on 3 surface of Graphene electrodes layer of the second pole plate of dried and clean again, being coated with out thickness is about 80 μm
Film, be put into coagulation forming in 25 DEG C of pure water at once and obtain temperature control type drug release hydrogel thin film 4.
The stacking knot that the first pole plate, temperature control type drug release hydrogel thin film and the second pole plate with microcellular structure are formed
The side (perpendicular to each face of the first pole plate and the second pole plate) of structure is encapsulated using PDMS.
Fibroin albumen film layer 2 in flexible substrates 1 with a thickness of 200nm-600nm, the thickness of Graphene electrodes layer 3
Degree is 50nm-150nm.
The temperature sensitive film of poly-N-isopropyl acrylamide therein, when 32 DEG C of temperature <, poly-N-isopropyl acrylamide water
Gel film is in the state of swelling, and drug molecule diffusion rate very little is still in solvent.When 32 DEG C of temperature >, poly- N-
Isopropylacrylamide hydrogel film sudden contraction, moisture and drug inside hydrogel discharge outward.
The above, preferable specific embodiment only of the invention, but scope of protection of the present invention is not limited thereto, appoints
Within the technical scope of the present disclosure, any changes or substitutions that can be easily thought of, all by what those familiar with the art
It should be included within the scope of the present invention.Therefore, protection scope of the present invention should be with the protection model of claims
Subject to enclosing.
Claims (10)
1. a kind of temperature control type flexible capacitive sensor for drug release, which is characterized in that including the first pole plate, the second pole plate
And temperature control type drug release hydrogel thin film positioned there between；First pole plate and the second pole plate includes: flexible base
The Graphene electrodes layer in fibroin albumen film layer and the fibroin albumen film layer on bottom, the flexible substrates；Described
Temperature control type drug release hydrogel thin film is the temperature sensitive film of poly-N-isopropyl acrylamide.
2. the temperature control type flexible capacitive sensor according to claim 1 for drug release, which is characterized in that described
The material of flexible substrates is one of PET, PI, PVA and PEN；The fibroin albumen film layer on the flexible substrates surface is made
For insulating layer.
3. the temperature control type flexible capacitive sensor according to claim 1 for drug release, which is characterized in that described
Graphene electrodes layer is that CVD graphene is first transferred to fibroin albumen thin-film surface, then utilizes reactive ion etching graphite
Alkene patterns；First pole plate has 10 μm -100 μm of aperture.
4. the temperature control type flexible capacitive sensor according to claim 1 for drug release, which is characterized in that described
Fibroin albumen thin film layer thickness in flexible substrates is 200nm-600nm, the Graphene electrodes layer with a thickness of
50nm-150nm。
5. the temperature control type flexible capacitive sensor according to claim 1 for drug release, which is characterized in that described
Temperature control type drug release hydrogel thin film is with a thickness of 5 μm -200 μm.
6. the temperature control type flexible capacitive sensor according to claim 1 for drug release, which is characterized in that described
The temperature sensitive film of poly-N-isopropyl acrylamide is pharmaceutical carrier, when the temperature increases, by poly N-isopropyl acrylamide gel
Network shrinks and discharges drug.
7. the temperature control type flexible capacitive sensor according to claim 1 for drug release, which is characterized in that described
Temperature control type drug release hydrogel thin film is formed in the Graphene electrodes layer surface of the second pole plate.
8. the temperature control type flexible capacitive sensor according to claim 1 for drug release, which is characterized in that described
The side for the stepped construction that first pole plate, temperature control type drug release hydrogel thin film and the second pole plate are formed is encapsulated using PDMS.
9. the preparation method of -8 any temperature control type flexible capacitive sensors for drug release according to claim 1,
It is characterized by comprising the following steps:
(1) the first pole plate and the second pole plate are prepared: preparing fibroin albumen film layer as insulating layer on flexible substrates surface, incites somebody to action
CVD graphene is transferred to fibroin albumen thin-film surface, then obtains graphene using reactive ion etching graphene pattern
Electrode layer；10 μm -100 μm of aperture is bored on first pole plate using laser drilling processes for drug release；
(2) the Graphene electrodes layer surface using the method for coating in the second pole plate is coated with poly-N-isopropyl acrylamide casting solution
Form temperature control type drug release hydrogel thin film；
(3) stacking of the first pole plate is set on the temperature control type drug release hydrogel thin film；
It is 200nm-600nm that the step (1), which is located at the fibroin albumen thin film layer thickness in flexible substrates, the graphene electricity
Pole layer with a thickness of 50nm-150nm, the temperature control type drug release hydrogel thin film of the step (2) is with a thickness of 5 μm -200 μm.
10. the preparation method of the temperature control type flexible capacitive sensor according to claim 9 for drug release, feature
It is, the stacking knot that first pole plate, temperature control type drug release hydrogel thin film and the second pole plate are formed using PDMS
The side of structure is packaged.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811092026.8A CN109141570B (en) | 2018-09-18 | 2018-09-18 | Temperature control type flexible capacitance sensor for drug release and preparation method |
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|---|---|---|---|
| CN201811092026.8A CN109141570B (en) | 2018-09-18 | 2018-09-18 | Temperature control type flexible capacitance sensor for drug release and preparation method |
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| CN109141570A true CN109141570A (en) | 2019-01-04 |
| CN109141570B CN109141570B (en) | 2020-04-07 |
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Cited By (3)
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| CN112442204A (en) * | 2020-11-13 | 2021-03-05 | 浙江理工大学 | Preparation method of flexible temperature sensor |
| CN113406154A (en) * | 2021-06-17 | 2021-09-17 | 哈尔滨工业大学 | Three-dimensional hydrogel-graphene-based biosensor and preparation method thereof |
| CN114873929A (en) * | 2022-05-18 | 2022-08-09 | 北京印刷学院 | Novel sensor material and preparation method thereof |
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| CN109141570B (en) | 2020-04-07 |
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