CN2786625Y - Micro sensor based on antibody-antigen method for examining liver fibrosis - Google Patents
Micro sensor based on antibody-antigen method for examining liver fibrosis Download PDFInfo
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- CN2786625Y CN2786625Y CN 200520041035 CN200520041035U CN2786625Y CN 2786625 Y CN2786625 Y CN 2786625Y CN 200520041035 CN200520041035 CN 200520041035 CN 200520041035 U CN200520041035 U CN 200520041035U CN 2786625 Y CN2786625 Y CN 2786625Y
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Abstract
The utility model belongs to the technical field of silicon micro machine and electrochemistry, particularly a minitype sensor based on an antibody-antigen method for examining liver fibrosis. The utility model is composed of a working electrode, a reference electrode, a counter electrode and a base plate, wherein the working electrode which forms a circular shape or which is similar to a circular shape is symmetrically arranged. The reference electrode forms a U shape and is arranged in the middle of the working electrode. The counter electrode forms a strip shape and is arranged in the middle of the reference electrode. The base plate is compositely formed by a silicon filling layer and a silicon dioxide layer. The number of the working electrode is from 4 to 8. The electrodes and the silicon dioxide layer are adhered by a titanium adhesion layer. The electrodes can be made by adopting conventional film-forming technology in IC technology. The minitype sensor of the utility model has the advantages of small volume, low cost and high detecting reliability. The utility model can quantitatively detect the antigen concentration in the blood serum and can detect a plurality of indicators of the blood serum simultaneously so as to reduce the consumption of the blood serum.
Description
Technical field
The utility model belongs to silicon micro mechanical and technical field of electrochemistry, is specifically related to a kind of microsensor based on antibody antigen method detection liver fibrosis of silicon micro mechanical processing.
Background technology
Liver fibrosis is meant that liver cell necroses and during inflammatory stimulus, the paraplasm pathologic process of fibrous connective tissue in the liver, and it is a chronic gradual process.The chronic liver disease overwhelming majority has liver fibrosis, and wherein 25%-40% finally develops into cirrhosis and even liver cancer.Therefore, the most important pathological characters of chronic liver disease is not only in liver fibrosis, also is the major reason that chronic hepatitis, cirrhosis etc. further develop, worsen.So find that early liver fibrosis is significant to the hepatopath.
At present the diagnostic method that adopts mainly comprises three kinds of imaging diagnosis, pathological diagnosis and serodiagnosises, and wherein serodiagnosis is because of the convenience of drawing materials, and is cheap, but and early diagnosis become the method that is most widely used at present.The antibody antigen method is one of most important method in the serum diagnostics.
The combination of antigen and antibody has the specificity and the sensitivity of height, the general requirement of making based on the classic method of this principle of sensor has bigger sample size (serum), and disposable use cost is too high, recycles cross pollution to make testing result unreliable.Thereby how to reduce the volume of sensor and reduce the problem demanding prompt solution that its cost becomes industrial production.
Summary of the invention
The purpose of this utility model is to provide the microsensor based on antibody antigen method detection liver fibrosis that a kind of volume is little, cost is low, detecting reliability is high.
The utility model design detect the microsensor of liver fibrosis based on the anti-source of antibody method, by working electrode, contrast electrode, electrode and substrate are formed, its structure is as depicted in figs. 1 and 2.Wherein, working electrode 3 is circle or sub-circular, 4-8 altogether, divide two rows to be symmetricly set in the substrate both sides, contrast electrode 1 is the U font, be arranged among two row's working electrodes 3 between, elongated to electrode 2, be arranged at the centre of U font contrast electrode 1; Substrate is composited by silicon substrate 5 and silicon dioxide layer 6, between each electrode and the silicon dioxide layer 6 titanium adhesion layer 7 is arranged.Adopt silicon dioxide layer, can make each electrode insulation effectively, do adhesion layer with titanium, not only can increase the adhesion strength of gold, silver electrode and silicon dioxide layer, also can make its partial oxygen that is exposed to electrode edge change into titania, and titania insulation and chemical inertness can not cause interference to measurement.
In the utility model, the diameter of working electrode 3 is 0.6-1.2mm, and mutual spacing is the 100-300 micron; The circular shape that the circle with working electrode 3 matches also can be made in the U font limit of contrast electrode 1, and contrast electrode 1 is the 100-300 micron with the spacing of each working electrode 3; Strip also can make the akin curve arc of inboard arc with contrast electrode 1 to electrode 2, with the distance on two limits of contrast electrode 1 be the 100-300 micron.
In the utility model, working electrode 3 can adopt gold electrode, covers the semi-insulating film 9 that different antibodies polymerization that one deck is used to detect forms above.Working electrode 1 is connected with contact (pin) 4 by lead-in wire.Contrast electrode 1 can adopt silver electrode, also covers one deck silver chloride 8 on it, makes the silver can be oxidized in air or sulfuration.Electrode 2 is adopted platinum electrode or gold electrode.
The microsensor of the utility model design when measuring with voltammetry, can make contrast electrode and working electrode and contrast electrode and more even to the electric current distribution between the electrode, thereby reduce measuring error.This size sensor is very little, but includes 4-6 working electrode, if the different antibody of polymerization just can be measured a plurality of indexs of serum simultaneously on each electrode, and only needs about 50 microlitre serum.
The utility model can adopt the conventional film-forming process (as evaporation, sputter etc.) in the IC technology to prepare various electrode films, and made electrode film is even, fine and close.Use photoetching process to make electrode forming, thereby electrode shape height unanimity, measuring error reduced.It not only can be qualitative, and the concentration of antigen in can detection by quantitative serum, thereby can estimate patient's the patient's condition better.Because manufacture craft is complete and the IC process compatible, can produce in enormous quantities easily, cost reduces greatly, thereby can disposablely use, and has avoided cross pollution, and accuracy rate is improved greatly.
Use the microsensor of the utility model design to detect three indexs of liver fibrosis, its response curve is seen Fig. 3-shown in Figure 6.Wherein use cyclic voltammetry copolymerization o-phenylenediamine (10mM) and hyaluronic acid binding protein (HABP), before the polymerization and the volt-ampere curve after the polymerization be respectively two closed curves, see shown in Figure 3.This sensor is to the response of the hyaluronic acid (HA) of variable concentrations, and along with concentration rises (from 20ng/ml-60ng/ml), the curve rule descends (seeing shown in Figure 4), shows that the antibody antigen reaction sends a telegraph resistance and increase.Sensor is to the response of variable concentrations IV collagen type (IV-C), and along with concentration rises (0.99ng/ml-9.65ng/ml), the curve rule descends (seeing shown in Figure 5), shows that the antibody antigen reaction sends a telegraph resistance and increase.Sensor is to the response of different depth and laminin (LN), and along with concentration rises (9.9ng/ml-107.1ng/ml), curve is rule and descends (seeing shown in Figure 6), shows that the antibody antigen reaction sends a telegraph resistance and increase.
Description of drawings
Fig. 1 is used for the sensor front schematic view that liver fibrosis detects.
Fig. 2 is used for the sensor diagrammatic cross-section that liver fibrosis detects.
Fig. 3 to Fig. 6 is the response curve with three indexs of this sensor liver fibrosis.
Fig. 3 is cyclic voltammetry copolymerization o-phenylenediamine (10mM) and hyaluronic acid binding protein (HABP), and two closed curves are respectively before the polymerization and the volt-ampere curve after the polymerization.
Fig. 4 is the response curve of sensor to variable concentrations hyaluronic acid (HA).
Fig. 5 is the response curve of sensor to variable concentrations IV collagen type (IV-C).
Fig. 6 is the response curve of sensor to variable concentrations and laminin (LN).
Number in the figure: 1 is contrast electrode, and 2 is to electrode, and 3 is working electrode, 4 is pressure welding point (pin), and 5 is silicon substrate, and 6 is silicon dioxide layer, 7 is the titanium adhesion layer, and 8 is silver chloride layer, and 9 for facing the semi-insulating film of phenylenediamine and liver fibrosis mark antibody with the cyclic voltammetry copolymerization.
Embodiment
Further describe the utility model below by embodiment.
Adopt evaporation back lift-off method to make this microsensor (electrode is also used gold electrode).Also can adopt replacement evaporations such as sputter, etch replaces lift-off to prepare.
A. with No. one, No. two liquid cleaning silicon chip successively and use deionized water rinsing, dry.
B. the SiO of hot growth 300nm
2
C. make the working electrode that needs by lithography and to electrode pattern, as depicted in figs. 1 and 2.Working electrode 3 is 6, the both sides symmetric offset spread, and diameter is 1mm, and spacing is 200 microns, and working electrode 3 is 200 microns with the spacing of contrast electrode 1, and contrast electrode 1 also is 200 microns with spacing to electrode 2.
D. evaporate titanium layer, the about 20nm of thickness evaporates gold subsequently, thickness 300nm.
E.lift-off gets needed working electrode and to electrode pattern.
F. make the contrast electrode figure that needs by lithography.
G. evaporate titanium layer, the about 20nm of thickness, evaporation subsequently is silver-colored, thickness 400nm.
H.lift-off gets needed working electrode and to electrode pattern.
I. encapsulation.
J. in NaCl solution, the anodizing about 200nm silver chloride layer 8 of one deck of on contrast electrode 1, growing.
K. the antibody (different antibodies is aggregated in the different operating electrode) of cyclic voltammetry copolymerization o-phenylenediamine (10mM) and hyaluronic acid binding protein (HABP) and other kind needs.
Promptly can be used for the measurement of serum index (about liver fibrosis) after finishing.
Claims (3)
1, a kind of microsensor that detects liver fibrosis based on the antibody antigen method, it is characterized in that by working electrode, contrast electrode, electrode and substrate are formed, wherein, working electrode 3 is circle or sub-circular, 4-8 altogether, divides two rows to be symmetricly set in the substrate both sides, contrast electrode (1) is the U font, between being arranged among two rows working electrodes (3), elongated to electrode (2), be arranged at the centre of U font contrast electrode (1); Substrate is composited by silicon substrate (5) and silicon dioxide layer (6), and titanium adhesion layer (7) is arranged between each electrode and the silicon dioxide layer (6).
2, microsensor according to claim 1, the diameter that it is characterized in that working electrode 3 is 0.6-1.2mm, mutual spacing is the 100-300 micron; The circular shape that the circle with working electrode 3 matches is made on the U font limit of contrast electrode (1), and contrast electrode (1) is the 100-300 micron with the spacing of each working electrode (3); Strip electrode (2) is made the akin curve arc of inboard arc with contrast electrode (1), with the distance on two limits of contrast electrode (1) be the 100-300 micron.
3, microsensor according to claim 1 is characterized in that working electrode (3) adopts gold electrode, covers the semi-insulating film of one deck (9) above; Contrast electrode (1) adopts silver electrode, covers one deck silver chloride (8) on it, and electrode (2) is adopted platinum electrode or gold electrode.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200520041035 CN2786625Y (en) | 2005-04-21 | 2005-04-21 | Micro sensor based on antibody-antigen method for examining liver fibrosis |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200520041035 CN2786625Y (en) | 2005-04-21 | 2005-04-21 | Micro sensor based on antibody-antigen method for examining liver fibrosis |
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| CN2786625Y true CN2786625Y (en) | 2006-06-07 |
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| CN 200520041035 Expired - Fee Related CN2786625Y (en) | 2005-04-21 | 2005-04-21 | Micro sensor based on antibody-antigen method for examining liver fibrosis |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100373157C (en) * | 2005-04-21 | 2008-03-05 | 复旦大学 | Micro sensor for detecting hepatic fibrosis based on method of antibody and antigen |
| CN106537130A (en) * | 2014-05-27 | 2017-03-22 | 卡斯西部储备大学 | Electrochemical sensor for analyte detection |
-
2005
- 2005-04-21 CN CN 200520041035 patent/CN2786625Y/en not_active Expired - Fee Related
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100373157C (en) * | 2005-04-21 | 2008-03-05 | 复旦大学 | Micro sensor for detecting hepatic fibrosis based on method of antibody and antigen |
| CN106537130A (en) * | 2014-05-27 | 2017-03-22 | 卡斯西部储备大学 | Electrochemical sensor for analyte detection |
| CN106537130B (en) * | 2014-05-27 | 2020-01-14 | 卡斯西部储备大学 | Electrochemical sensor for analyte detection |
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Legal Events
| Date | Code | Title | Description |
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| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C19 | Lapse of patent right due to non-payment of the annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |