CN108845012A - A kind of conducting polymer microneedle electrodes and preparation method thereof for biomolecule detection - Google Patents

A kind of conducting polymer microneedle electrodes and preparation method thereof for biomolecule detection Download PDF

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CN108845012A
CN108845012A CN201810350383.3A CN201810350383A CN108845012A CN 108845012 A CN108845012 A CN 108845012A CN 201810350383 A CN201810350383 A CN 201810350383A CN 108845012 A CN108845012 A CN 108845012A
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micropin
conducting polymer
microneedle electrodes
biomolecule detection
solid
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郭新东
金旋
杨圆
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Beijing University of Chemical Technology
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Beijing University of Chemical Technology
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/28Electrolytic cell components
    • G01N27/30Electrodes, e.g. test electrodes; Half-cells
    • G01N27/327Biochemical electrodes, e.g. electrical or mechanical details for in vitro measurements
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/28Electrolytic cell components
    • G01N27/30Electrodes, e.g. test electrodes; Half-cells
    • G01N27/307Disposable laminated or multilayered electrodes

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Abstract

The conducting polymer microneedle electrodes and preparation method thereof that the present invention relates to a kind of for biomolecule detection.Conducting polymer microneedle electrodes for biomolecule detection are the integrated electrode products of electrode and micropin, are made of polymeric solid micropin, inert metal layer, the conductive polymer film for being fixed with bioactive molecule.One layer of conducting polymer film of electrochemical deposition on polymer micro needle is pierced into subcutaneously using micropin, realizes the acquisition of bioelectrical signals, have the characteristics that efficient, painless.Bioactive ingredients are fixed in conducting polymer film by the present invention, are carried out specific recognition to biomolecule to be detected, are greatly improved the sensitivity of electric signal.Conducting polymer microneedle electrodes preparation process of the present invention is simple, cheap, and after being pierced into skin, conducting polymer has good biocompatibility and insoluble in the continuous monitoring of real-time detection and long-time in vivo, being conducive to biomolecule.

Description

A kind of conducting polymer microneedle electrodes and preparation method thereof for biomolecule detection
Technical field
The invention belongs to bioelectrical signals detection technique field, it particularly relates to a kind of for biomolecule detection Conducting polymer microneedle electrodes and preparation method thereof, the electrode by polymeric solid micropin, inert metal layer, be fixed with biology The conducting polymer film layer of bioactive molecule is constituted.
Background technique
In recent years, with MEMS (MEMS:Micro-Electro-Mechanical Systems) technology is not Disconnected development and maturation, so that the application range of microsensor constantly expands, are widely used in the fields such as medicine, environment measuring, base It is also rapidly developed therewith in the research of the probe microelectrode of micro fabrication.
The difficult point that electrode currently used for biomolecule detection encounters in signal acquisition has (1) bioelectrical signals weak; (2) signal source impedance is high, and organism and interelectrode interface are complicated, and the unstable factors such as polarization, noise and interference are not easy to control. These difficult points how are solved, the sensitivity of bioelectrical signals is improved, improving signal-to-noise ratio and expanding its application range is bioelectricity The core of pole research field.
Thrust-type microneedle electrodes efficiently solve the problems, such as skin high impedance, realize the acquisition of bioelectrical signals, such as specially Sharp CN103263727, CN102727992A, US20100130940 and CN1415385A, mainly using metal micro-needle electricity Pole, mechanical property is good, easily pierces through the fine and close cuticula of skin, but metal material Electrode-biofilm compatibility is bad, long-term to be pierced into Skin can cause skin allergy, inflammation, and the rejection effect of body can promote leucocyte to be largely enriched in microneedle surface, influence The acquisition of bioelectrical signals, and preparation process is complicated, at high cost, structure design is low with the flexibility of application.
Therefore, it in order to overcome the problems, such as microneedle electrodes signal acquisition and electrode material biocompatibility, needs to prepare one kind Good biocompatibility, the microneedle electrodes of high sensitivity.Conducting polymer has good conductive property under dopant effect, will Bioactive molecule is fixed on conducting polymer, and bioactive molecule will not be denaturalized or inactivate, can specific recognition biology Molecule, the effective sensitivity for improving electric signal.Conducting polymer microneedle electrodes are the integration products of micropin and electrode, are utilized Micropin is pierced into skin, while realizing the acquisition of bioelectrical signals.
Summary of the invention
In order to solve the above technical problems, the present invention provides a kind of conducting polymer micropin electricity for biomolecule detection Pole and preparation method thereof.
A kind of conducting polymer microneedle electrodes for biomolecule detection, which is characterized in that including:Polymeric solid is micro- Needle, inert metal layer and the conductive polymer film layer for being fixed with bioactive molecule.Bioactivity in conducting polymer film Molecule can to biomolecule specific recognition to be detected, thus with sensitivity acquisition specific reaction during generate electric current, Collected signal is passed to information by external circuits and records processing system, to realize by voltage, inductance and electric quantity signal Detection and continuous monitoring to biomolecule content.
Preferably, the sensitivity of the microneedle electrodes be by change micropin material, micropin length, micropin base diameter, The distance between micropin draw ratio, micropin and one of conducting polymer film thickness a variety of are realized.
Preferably, the needle body of the polymeric solid micropin and pedestal are integrally melted by biodegradable high molecular material Type is made;The material of the polymeric solid micropin includes one of polylactic acid, l-lactic acid and polyglycolic acid or more Kind;The needle body length of the polymeric solid micropin is between 200-1000 microns;The bottom of the polymeric solid micropin Seat diameter is between 10-800 microns.
Preferably, the inert metal layer is prepared by one of sputtering, spraying, dip-coating and deposition method, is wrapped Include one of Au Ag Pt Pd, iridium and tin indium oxide or a variety of, the thickness of the inert metal layer between 1-10 microns, Production method is that one layer of exposure mask is covered on solid micropin pedestal, and only the unlapped region of exposure mask applies on micropin needle body and pedestal It is covered with inert metal layer, the inert metal layer being coated on micropin pedestal includes contact or the conduction for external circuits Route.
Preferably, the conductive polymer film for being fixed with bioactive molecule is made up of electrochemical polymerization, Bioactive molecule or bioactive molecule solution are directly added to the solution containing conductive high polymer monomer He its dopant In, the conductive polymer film for being fixed with bioactive molecule is obtained by the method one-step polymerization of electrochemical polymerization;The electricity Chemical polymerization process includes one of cyclic voltammetry, potentiostatic method, galvanostatic method, potentiodynamic method, impulse method or more Kind.
Preferably, the conductive polymer film layer is by polyphenylethylene, polyaniline, polypyrrole, polythiophene and its derivative One of object or a variety of compositions, thickness is between 1-200 microns.
Preferably, dopant used in the conductive polymer film is chloride ion, sulfate radical, nitrate anion, tetrafluoro boron One in acid group, tosilate, anthraquinone sulfonic acid, polyvinyl sulfuric acid salt, polyvinyl alcohol, benzene acid iodide and poly styrene sulfonate Kind is a variety of.
Preferably, the bioactive molecule is one of enzyme, protein, microorganism and DNA or a variety of.
Preferably, the micropin in the microneedle electrodes is one of single micropin, microneedle array and micropin combination pattern Or it is a variety of.
The preparation method of the conducting polymer microneedle electrodes of above-mentioned biomolecule detection, includes the following steps:
(1) the polymeric solid micropin or solid microneedle array of pedestal are had with template preparation;
(2) exposure mask with circuit pattern is overlying on micropin pedestal, using sputtering, spraying, dip-coating or deposition method solid Inert metal layer is covered on body micropin needle body and its pedestal, then thickness removes exposure mask between 1-10 microns;
(3) solution containing conductive high polymer monomer and dopant is prepared, by bioactive molecule or bioactive molecule Solution is added in prepared solution, is mixed and stirred for that uniformly, then uniformly mixed solution being added in electrolytic cell;
(4) the solid micropin with pedestal is completely immersed in electrolytic cell, working electrode is connected with inert metal layer, is adopted Electrochemical polymerization 20-1000min is carried out with cyclic voltammetry, potentiostatic method, galvanostatic method, potentiodynamic method or impulse method, Solid micropin is taken out from electrolytic cell later, the conducting polymer microneedle electrodes for being fixed with bioactive molecule can be obtained.
Conducting polymer microneedle electrodes provided by the present invention for biomolecule detection are that electrode is integrated with micropin Electrode product, one layer of conducting polymer film of electrochemical deposition on polymer micro needle are pierced into subcutaneous, realization bioelectricity using micropin The acquisition of signal has the characteristics that efficient, painless.Bioactive ingredients are fixed in conducting polymer film by the present invention, are treated It detects biomolecule and carries out specific recognition, greatly improve the sensitivity of electric signal.Conducting polymer of the present invention Microneedle electrodes preparation process is simple, cheap, and after being pierced into skin, conducting polymer has good biocompatibility and do not dissolve in In vivo, be conducive to the real-time detection and continuous monitoring for a long time of biomolecule.It is of the present invention for biomolecule detection Conducting polymer microneedle electrodes, good biocompatibility, high sensitivity do not dissolve in vivo, can be to biomolecule real-time detection or length Time Continuous monitoring.The poor biocompatibility that other microneedle electrodes are faced is efficiently solved, electrical signal collection is difficult, preparation Complex process, the high problem of cost.
Detailed description of the invention
Fig. 1 is conducting polymer microneedle electrodes schematic diagram of the present invention;
Fig. 2 is the macromolecule micropin with pedestal;
Fig. 3 is the macromolecule micropin that outer surface is covered with inert metal layer;
Fig. 4 is the electrochemical polymerization conducting polymer film schematic diagram in electrolytic cell;
Fig. 5 is the top view for being carved with circuit pattern exposure mask.
1. solid micropin needle body in figure, 2. solid micropin pedestals, 3. inert metal layers, 4. working electrodes, 5. pairs of electrodes, 6. Auxiliary electrode, 7. electrolytic cells, 8. are fixed with the electroconductive polymer layer of bioactive molecule, 9. exposure masks.
Specific embodiment
The present invention will be further described in the following with reference to the drawings and specific embodiments, but protection scope of the present invention and not only It is limited to this.
【Embodiment 1】
(1) by the polydimethylsiloxane prepolymer object and curing agent of liquid in mass ratio 10:1 mixing, takes out after mixing evenly Bubble therein is removed in vacuum, is then poured into horizontal positioned container, which is put into 60 DEG C of baking oven and is added Hot 5-10h can obtain the uniform dimethyl silicone polymer thin slice of thickness;Then the thin slice is taken out from container and is put into laser carving In quarter machine working bin, laser parameter is adjusted by required solid micropin geometric shape, micro-nano is carried out to dimethyl silicone polymer thin slice Meter Jia Gong, to prepare microneedles template;
(2) suitable polylactic acid solid particle is placed on microneedles template, is then put into template in 200 DEG C of baking oven Heating a period of time, template is taken out after polylactic acid sufficiently melts, compression molding when taking advantage of polylactic acid melting takes off after being cooled to room temperature The solid macromolecule micropin with pedestal can be obtained in mould;
(3) exposure mask for being carved with certain circuit pattern as shown in Figure 5 is covered on solid micropin pedestal, then using leaching Conductive silver glue is uniformly overlying on solid micropin outer surface, removes exposure mask after being dried at room temperature for 3h, obtain outer surface by the method for painting Be coated with the solid micropin (as shown in Figure 3) of conductive silver glue, wherein conductive silver glue with a thickness of 1-10 microns.
It (4) is 6 by mass ratio:4 polypyrrole monomer and sodium apolate is configured to 20mL solution, into acquired solution The glucose oxidase of 200 active units is added, is uniformly mixed;
(5) solution obtained by (4) is added in electrolytic cell, micropin obtained by (3) is connected with working electrode, then will It is totally immersed in electrolytic cell, will connect to electrode with auxiliary electrode correct rear using potentiostatic method progress electrochemical polymerization (as shown in Figure 4), wherein polymerization current potential is 0.8V, polymerization time 90min.Micropin is taken out after the completion of polymerization, is rushed with ultrapure water Gained micropin is washed 3-5 times to get the microneedle electrodes of conducting polymer film (being fixed with glucose oxidase) are covered with (such as Fig. 1 institute Show), wherein conducting polymer film with a thickness of 1-200 microns.
【Embodiment 2】
(1) by the polydimethylsiloxane prepolymer object and curing agent of liquid in mass ratio 10:1 mixing, takes out after mixing evenly Bubble therein is removed in vacuum, is then poured into horizontal positioned container, which is put into 60 DEG C of baking oven and is added Hot 5-10h can obtain the uniform dimethyl silicone polymer thin slice of thickness;Then the thin slice is taken out from container and is put into laser carving In quarter machine working bin, laser parameter is adjusted by required solid micropin geometric shape, micro-nano is carried out to dimethyl silicone polymer thin slice Meter Jia Gong, to prepare microneedles template;
(2) suitable polylactic acid solid particle is placed on microneedles template, is then put into template in 200 DEG C of baking oven Heating a period of time, template is taken out after polylactic acid sufficiently melts, compression molding when taking advantage of polylactic acid melting is cooled to room temperature to it The solid macromolecule micropin with pedestal can be obtained in demoulding afterwards;
(3) exposure mask for being carved with certain circuit pattern as shown in Figure 5 is covered on solid micropin pedestal, then with small-sized Ion sputtering instrument to solid microneedle surface carry out metal spraying processing, so that its surface is plated one layer of gold thin film, remove later exposure mask to get The solid macromolecule micropin of surface gold-plating.
It (4) is 6 by mass ratio:4 polypyrrole monomer and sodium apolate is configured to 20mL solution, into acquired solution The glucose oxidase of 200 active units is added, is uniformly mixed;
(5) solution obtained by (4) is added in electrolytic cell, micropin obtained by (3) is connected with working electrode, then will It is totally immersed in electrolytic cell, will connect to electrode with auxiliary electrode correct rear using galvanostatic method progress electrochemical polymerization (as shown in Figure 4), wherein polymerization electric current is 5mA, polymerization time 60min.Micropin is taken out after the completion of polymerization, uses ultrapure water Gained micropin 3-5 times to get the microneedle electrodes (as shown in Figure 1) for being covered with conducting polymer film (being fixed with glucose oxidase), Wherein conducting polymer film with a thickness of 1-200 microns.
The conducting polymer microneedle electrodes that can be used for detecting glucose content have been prepared according to the above method.
It is understood that the principle that embodiment of above is intended to be merely illustrative of the present and the exemplary implementation that uses Mode, however the present invention is not limited thereto.For those skilled in the art, essence of the invention is not being departed from In the case where mind and essence, various changes and modifications can be made therein, these variations and modifications are also considered as protection scope of the present invention.

Claims (10)

1. a kind of conducting polymer microneedle electrodes for biomolecule detection, which is characterized in that including:Polymeric solid is micro- Needle, inert metal layer and the conductive polymer film layer for being fixed with bioactive molecule.
2. the conducting polymer microneedle electrodes according to claim 1 for biomolecule detection, which is characterized in that described The sensitivity of microneedle electrodes is by between change micropin material, micropin length, micropin base diameter, micropin draw ratio, micropin Distance and one of conducting polymer film thickness or a variety of realize.
3. the conducting polymer microneedle electrodes according to claim 2 for biomolecule detection, which is characterized in that described The needle body and pedestal of polymeric solid micropin are made of biodegradable high molecular material integrated molding;The macromolecular solid The material of body micropin includes one of polylactic acid, l-lactic acid and polyglycolic acid or a variety of;The polymeric solid The needle body length of micropin is between 200-1000 microns;The base diameter of the polymeric solid micropin is in 10-800 micron Between.
4. the conducting polymer microneedle electrodes according to claim 3 for biomolecule detection, which is characterized in that described Inert metal layer is prepared by one of sputtering, spraying, dip-coating and deposition method, including Au Ag Pt Pd, iridium and oxygen Change one of indium tin or a variety of, for the thickness of the inert metal layer between 1-10 microns, production method is in solid micropin One layer of exposure mask is covered on pedestal, only the unlapped region coating of exposure mask has inert metal layer on micropin needle body and pedestal, described The inert metal layer being coated on micropin pedestal include contact or conducting wire for external circuits.
5. the conducting polymer microneedle electrodes according to claim 4 for biomolecule detection, which is characterized in that described The conductive polymer film for being fixed with bioactive molecule is made up of electrochemical polymerization, directly by bioactive molecule or Bioactive molecule solution is added in the solution containing conductive high polymer monomer and its dopant, passes through the side of electrochemical polymerization Method one-step polymerization obtains the conductive polymer film for being fixed with bioactive molecule;The electrochemical polymerization includes circulation volt One of An Fa, potentiostatic method, galvanostatic method, potentiodynamic method, impulse method are a variety of.
6. the conducting polymer microneedle electrodes according to claim 5 for biomolecule detection, which is characterized in that described Conductive polymer film layer is by one of polyphenylethylene, polyaniline, polypyrrole, polythiophene and its derivative or a variety of structures At thickness is between 1-200 microns.
7. the conducting polymer microneedle electrodes according to claim 6 for biomolecule detection, which is characterized in that described Dopant used in conductive polymer film is chloride ion, sulfate radical, nitrate anion, tetrafluoroborate, tosilate, anthracene One of quinone sulfonic acid, polyvinyl sulfuric acid salt, polyvinyl alcohol, benzene acid iodide and poly styrene sulfonate are a variety of.
8. the conducting polymer microneedle electrodes according to claim 7 for biomolecule detection, which is characterized in that described Bioactive molecule is one of enzyme, protein, microorganism and DNA or a variety of.
9. the conducting polymer microneedle electrodes according to claim 8 for biomolecule detection, which is characterized in that described Micropin in microneedle electrodes is one of single micropin, microneedle array and micropin combination pattern or a variety of.
10. a kind of preparation method of the conducting polymer microneedle electrodes for biomolecule detection, which is characterized in that including following Step:
(1) the polymeric solid micropin or solid microneedle array of pedestal are had with template preparation;
(2) exposure mask with circuit pattern is overlying on micropin pedestal, it is micro- in solid using sputtering, spraying, dip-coating or deposition method Inert metal layer is covered on needle needle body and its pedestal, then thickness removes exposure mask between 1-10 microns;
(3) solution containing conductive high polymer monomer and dopant is prepared, by bioactive molecule or bioactive molecule solution It is added in prepared solution, is mixed and stirred for that uniformly, then uniformly mixed solution being added in electrolytic cell;
(4) it will be completely immersed in electrolytic cell with the solid micropin of pedestal, working electrode be connected with inert metal layer, using following Ring voltammetry, potentiostatic method, galvanostatic method, potentiodynamic method or impulse method carry out electrochemical polymerization 20-1000min, later Solid micropin is taken out from electrolytic cell, and the conducting polymer microneedle electrodes for being fixed with bioactive molecule can be obtained.
CN201810350383.3A 2018-04-18 2018-04-18 A kind of conducting polymer microneedle electrodes and preparation method thereof for biomolecule detection Pending CN108845012A (en)

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CN110201296A (en) * 2019-05-20 2019-09-06 北京化工大学 A kind of conducting polymer microneedle patch and preparation method thereof for controlled drug release
CN110522460A (en) * 2019-09-29 2019-12-03 清华大学深圳国际研究生院 Multi-index detection sensor based on transdermal microneedle array and preparation method
CN113777145A (en) * 2021-09-14 2021-12-10 北京大学 Method for manufacturing micro-needle biosensor
CN113977829A (en) * 2021-09-08 2022-01-28 北京宝理泰科技有限公司 Preparation method of hollow microneedle array biosensor
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CN110522460A (en) * 2019-09-29 2019-12-03 清华大学深圳国际研究生院 Multi-index detection sensor based on transdermal microneedle array and preparation method
CN113977829A (en) * 2021-09-08 2022-01-28 北京宝理泰科技有限公司 Preparation method of hollow microneedle array biosensor
CN113777145A (en) * 2021-09-14 2021-12-10 北京大学 Method for manufacturing micro-needle biosensor
CN115092875A (en) * 2022-06-17 2022-09-23 上海烨映微电子科技股份有限公司 Microneedle chip and method for producing same

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Application publication date: 20181120