CN1192230C - Sensor capable of detecting several biological indexes simultaneously - Google Patents
Sensor capable of detecting several biological indexes simultaneously Download PDFInfo
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- CN1192230C CN1192230C CN 01132053 CN01132053A CN1192230C CN 1192230 C CN1192230 C CN 1192230C CN 01132053 CN01132053 CN 01132053 CN 01132053 A CN01132053 A CN 01132053A CN 1192230 C CN1192230 C CN 1192230C
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Abstract
The present invention relates to a capacitive sensor which is capable of simultaneously detecting various biologic indexes. The capacitive sensor of the present invention is composed of an insulating matrix and a microelectrode array with a plurality of metal electrodes, wherein the microelectrode array is fixed on the insulating matrix and is chemically modified. The present invention also discloses a preparation method of the microelectrodes and an application thereof. The dynamics processes of specific combination among biologic macromolecules are monitored by the capacitive sensor of the present invention according to real-time detection, so that the present invention has the advantages of high accuracy of disease detection, high safety and reliability and high flux, and can hugely satisfy the requirements of clinical diagnosis.
Description
Technical field
The present invention relates to technical field of biological.Be specifically related to a kind of sensor that can detect multiple Biological indicators simultaneously.
Background technology
Biology sensor is a kind of high-tech product that integrates modern biotechnology and advanced person's electronic technology, is a kind of new sensor technology that grows up in nearly decades.Someone calls the century of life science and the century of information science to 21 century.The cross discipline that biology sensor grows up between life science and information science just.In traditional sensor, the signal receptor is made up of non-living matter fully.And the difference of the maximum of biology sensor and traditional various physical sensors and chemical sensor is to contain living substance in the receptor of biology sensor.For example, certain vegetable cell or zooblast as perceptron, can be made various cell sensors; Can be made into tissus sensor (or being called tissue electrode) with biological tissue as receptor; The organelle that some are specific is separated as receptor in cell, can be made into cell organelle sensor; Microorganism be can be made into microbiological sensor as receptor; And with biomolecule such as protein, nucleic acid etc. as receptor, more become the main flow of contemporary biology sensor development.
But most biology sensors all can only detect the single creature index, can not detect a plurality of Biological indicators simultaneously.As glucose sensor, amperometric biosensor etc.In the clinical diagnosis field, the detection of single Biological indicators has little significance to medical diagnosis on disease, because nearly all single index all can not be corresponding with disease single-mindedly, so a plurality of indexs of correlation to disease detect, can improve the accuracy of diagnosis greatly, thereby make the doctor can in time take correct therapeutic scheme, propose to detect the pressing for of biology sensor of many indexs clinically.
Summary of the invention
Technical matters to be solved by this invention provides a kind of high flux, detects accurately, and is reliable, highly sensitive, can detect the capacitive transducer of multiple Biological indicators simultaneously.
Capacitive transducer of the present invention is made up of with being fixed on the dielectric substrate and through the microelectrode array with a plurality of metal electrodes of chemical modification dielectric substrate.
Wherein, chemical modification is meant and forms insulation course, crosslinking chemical layer and biological membrane successively on metal electrode.Insulation course is formed in conjunction with compounds containing thiol groups by surface of metal electrode; The crosslinking chemical layer is formed in conjunction with crosslinking chemical by surface of insulating layer, this crosslinking chemical not only can with insulation course on contain the compound covalent bond of sulfydryl, and can the covalent bond biomacromolecule; Biological membrane is to combine biomacromolecule and the unimolecular layer that forms at the crosslinking chemical laminar surface, and does not influence the biologically active of biomacromolecule.
Dielectric substrate of the present invention is preferably from epoxy resin board, plastic plate, polyvinyl chloride panel or glass carrier etc.
Metal electrode described in the present invention is conducting metals such as gold, silver.
Biomacromolecule described in the present invention on the biological membrane is selected from antigen, antibody or enzyme etc., and this biomacromolecule can produce specificity and combine with the predetermined substance in the human body fluid.
The detection principle of capacitive transducer of the present invention is to be based upon the theoretic a kind of sensing technology of electrostatic double layer.
Because the absorption of material and the change of surface charge all produce appreciable impact to double electrical layers, it is different that the material of variable concentrations is combined in the capacitance variations that causes on the electrode.So, material concentration in tested body fluid is not simultaneously, this material combines the capacitance variations situation that produces with biomacromolecule specificity on the electrode also inequality, and when material concentration within the specific limits the time, the rate of change of capacitance of this electrode becomes positive correlation with material concentration.So,, can learn the specific substance concentration of tested body fluid if utilize capacitor to detect rate of change of capacitance in real time.Because capacitive transducer of the present invention contains a plurality of electrodes, has all formed the unimolecular film of biomacromolecule on each electrode, so this capacitive transducer can be used for measuring simultaneously the concentration of multiple predetermined substance in the tested body fluid.
Another technical matters to be solved by this invention provides the preparation method of above-mentioned capacitive transducer.
The preparation method of capacitive transducer of the present invention comprises the following steps:
1) on dielectric substrate, plates a plurality of disjunct metal electrodes, form electrode microarray, and the plain conductor of each electrode is led to capacitor can survey the position with a definite sequence; (see figure 2)
2) be that room temperature was cleaned 3-10 minute in 7: 3 the 95% concentrated sulphuric acid-superoxol, anhydrous alcohol, secondary water in volume ratio successively with the dielectric substrate behind the plated electrode, and dry up;
3) add certain density compounds containing thiol groups solution on this dielectric substrate surface, liquor capacity enough soaks into all electrode surfaces, room temperature assembling 3-24 hour;
4) successively in anhydrous alcohol, secondary water room temperature cleaned 3-10 minute;
5) add certain density glutaraldehyde on this dielectric substrate surface, or 1-ethyl-3-(3-dimethylamino-propyl) carbodiimide solution, liquor capacity enough soaks into all electrode surfaces, room temperature assembling 3-24 hour;
6) successively in anhydrous alcohol, secondary water room temperature cleaned 3-10 minute;
7) add the different solution that contains excessive biomacromolecule at each electrode surface, 37 degree assemblings 3-24 hour;
8) adding the quality percent by volume on this dielectric substrate surface is the 0.05-0.5% bovine serum albumin solution, and liquor capacity enough soaks into all electrode surfaces, room temperature sealing 2 hours;
9) capacitive transducer for preparing being positioned over the 2-8 degree stores standby.
The preferred MUA of the compounds containing thiol groups that the present invention selects for use (11-mercaptoundecanoicacid) (11-sulfydryl undecanoic acid), sulfydryl ethylenediamine, amino thiophenol, hexadecane mercaptoalcohol etc.
A further object of the present invention is to disclose above-mentioned capacitive transducer to detect application in the multiple Biological indicators at the same time.
The disease that the detectable Biological indicators of capacitive transducer of the present invention relate to includes but not limited to immune disease, communicable disease, tumour.
Capacitive transducer of the present invention is realized disease detection by following manner:
1) prepares manyly simultaneously, make that each electrode in every pair of capacitive transducer is consistent with biomacromolecule kind, the quantity that its comparative electrode contains, every pair of capacitive transducer is put into a reaction vessel (see figure 1) identical capacitive transducer.
2) (annotate: this solution is the mixed solution of the material that can combine with biomacromolecule specificity on the electrode with the mixed solution of variable concentrations, and each material concentration is known) inject different reaction vessels respectively, liquor capacity is enough to make all electrode submergences on the capacitive transducer, places 2-30 minute.Detect capacitance on each electrode in real time by capacitor, according to the relation value curve plotting of rate of change of capacitance (Δ C/C) with the time (t), obtain the relation curve of (Δ C/C)/t and each material concentration thus, this curve is typical curve.
3) body fluid to be measured is injected a reaction vessel, the body fluid volume is enough to make all electrode submergences on the capacitive transducer, places 2-30 minute.Detect capacitance on each test electrode in real time by capacitor, according to the relation value curve plotting of rate of change of capacitance (Δ C/C) with the time (t), obtain (Δ the C/C)/t value of each material by curve, the standard of comparison curve can obtain the concentration of each material in the body fluid.
4) measured material concentration is compared with the concentration range of this material in normal person's body fluid, thereby judge whether the measured suffers from corresponding disease.
Description of drawings
Fig. 1 has been equipped with the synoptic diagram of the reaction vessel of capacitive transducer.
Wherein 4 is reaction vessel, and 5 is microelectrode array, and 6 is solution to be measured, and 7 is the external capacitor detecting device.
Fig. 2 capacitive transducer synoptic diagram.
Wherein 1 for connecting lead, and 2 is metal electrode, forms insulation course, crosslinking chemical layer and biological membrane successively outside electrode, and 3 is dielectric substrate.
Further describe the testing process of capacitive transducer below in conjunction with accompanying drawing:
As shown in Figure 2, form insulation course, crosslinking chemical layer and biological membrane on the metal electrode 2 successively, and be fixed on the dielectric substrate 3, when a pair of capacitive transducer places the electrode that combines same biomacromolecule in 4, two microelectrode arrays of reaction vessel relative.
Body fluid to be measured is injected reaction vessel 4, microelectrode array 5 is dipped in the body fluid to be measured reacts.Detect capacitance on each electrode in real time by capacitor, according to the relation value curve plotting of rate of change of capacitance (Δ C/C) with the time (t), gained (Δ C/C)/t contrasts corresponding standard curve, can this body fluid in the concentration of each material.
The present invention is a kind of capacitive transducer that can detect multiple Biological indicators simultaneously, instrument according to real-time detection, come the dynamic process of specificity combination between the big molecule of monitoring bio, make and detect the accuracy of disease height, safe and reliable, and can have the capacitive transducer of different index combinations according to user's demand preparation, thus have high flux property and broad applicability, and preparation cost is lower, has broad application prospects in the clinical diagnosis field.
Embodiment
Metal electrode is a gold electrode, and its surface is a square, and area is 1mm
2, lead is superfine spun gold.
Preparation process is as follows:
1. plate above-mentioned electrode in the surface of glass slide of 10mm*10mm with the square formation of 4*3, the centre distance of each electrode is 1.5mm, forms electrode microarray;
2. slide is successively at the concentrated sulphuric acid: the solution of hydrogen peroxide=7: 3, and anhydrous alcohol cleans in the secondary water, and room temperature dries up;
3. slide is dipped in 1.0mM MUA solution, assembles room temperature 12 hours;
4. slide cleans room temperature 10 minutes with anhydrous alcohol, secondary water successively;
5. be dipped in 0.5% glutaraldehyde solution, assembled room temperature 10 minutes 12 hours;
6. slide cleans room temperature 10 minutes with anhydrous alcohol, secondary water successively;
7. each electrode surface is added different antibody-solutions, antibody concentration is 0.1mg/ml-15mg/ml, 37 degree assemblings 12 hours.Antibody comprises: β HCG, PSA, free PSA, hGH, AFP, CEA, CA12-5, CA15-3, CA19-9, CA242, NSE, Ferritin;
8. slide is dipped in the 0.1%BSA solution and sealed 2 hours;
9. the capacitive transducer for preparing being put in the 2-8 degree stores for future use.
Claims (5)
1, a kind of capacitive transducer that can detect multiple Biological indicators simultaneously, it is characterized in that this sensor is by dielectric substrate be fixed on the dielectric substrate and form through the microelectrode array with a plurality of metal electrodes of chemical modification, described chemical modification is meant and forms insulation course, crosslinking chemical layer and biological membrane successively that on metal electrode wherein insulation course is formed in conjunction with compounds containing thiol groups by surface of metal electrode; The crosslinking chemical layer is formed in conjunction with crosslinking chemical by surface of insulating layer, this crosslinking chemical not only can with insulation course on contain the compound covalent bond of sulfydryl, and can the covalent bond biomacromolecule; Biological membrane is to combine biomacromolecule and the unimolecular layer that forms at the crosslinking chemical laminar surface, and does not influence the biologically active of biomacromolecule.
2, a kind of capacitive transducer that can detect multiple Biological indicators simultaneously as claimed in claim 1 is characterized in that wherein said metal electrode is gold or silver-colored conducting metal.
3, a kind of capacitive transducer that can detect multiple Biological indicators simultaneously as claimed in claim 1 is characterized in that the biomacromolecule on the wherein said biological membrane is selected from antigen, antibody or enzyme.
4, a kind of capacitive transducer that can detect multiple Biological indicators simultaneously as claimed in claim 1 is characterized in that wherein said dielectric substrate is selected from epoxy resin board, plastic plate, polyvinyl chloride panel or glass carrier.
5, a kind ofly prepare the method that can detect the capacitive transducer of multiple Biological indicators simultaneously as claimed in claim 1, it is characterized in that this preparation method comprises the following steps:
1) on dielectric substrate, plates a plurality of disjunct metal electrodes, form electrode microarray, and the plain conductor of each electrode is led to capacitor can survey the position with a definite sequence;
2) be that room temperature was cleaned 3-10 minute in 7: 3 the 95% concentrated sulphuric acid-superoxol, anhydrous alcohol, secondary water in volume ratio successively with the dielectric substrate behind the plated electrode, and dry up;
3) add certain density compounds containing thiol groups solution on this dielectric substrate surface, liquor capacity enough soaks into all electrode surfaces, room temperature assembling 3-24 hour;
4) successively in anhydrous alcohol, secondary water room temperature cleaned 3-10 minute;
5) add certain density glutaraldehyde on this dielectric substrate surface, or 1-ethyl-3-(3-dimethylamino-propyl) carbodiimide solution, liquor capacity enough soaks into all electrode surfaces, room temperature assembling 3-24 hour;
6) successively in anhydrous alcohol, secondary water room temperature cleaned 3-10 minute;
7) add the different solution that contains excessive biomacromolecule at each electrode surface, 37 degree assemblings 3-24 hour;
8) adding the quality percent by volume on this dielectric substrate surface is the 0.05-0.5% bovine serum albumin solution, and liquor capacity enough soaks into all electrode surfaces, room temperature sealing 2 hours;
9) capacitive transducer for preparing being positioned over the 2-8 degree stores standby.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 01132053 CN1192230C (en) | 2001-10-30 | 2001-10-30 | Sensor capable of detecting several biological indexes simultaneously |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 01132053 CN1192230C (en) | 2001-10-30 | 2001-10-30 | Sensor capable of detecting several biological indexes simultaneously |
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| CN1417577A CN1417577A (en) | 2003-05-14 |
| CN1192230C true CN1192230C (en) | 2005-03-09 |
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| CN 01132053 Expired - Fee Related CN1192230C (en) | 2001-10-30 | 2001-10-30 | Sensor capable of detecting several biological indexes simultaneously |
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Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101144809B (en) * | 2007-10-17 | 2013-02-27 | 中国科学院光电技术研究所 | Method for manufacturing high-sensitivity nano biosensor |
| KR101338175B1 (en) * | 2012-01-13 | 2013-12-09 | 주식회사 아이센스 | Cartridge for sensing elements in a sample |
| CN103472237B (en) * | 2013-09-18 | 2015-02-25 | 四川大学华西第二医院 | Bio-sensitive chip as well as preparation method and use thereof |
| CN107224365A (en) * | 2017-05-26 | 2017-10-03 | 杭州博博科技有限公司 | A kind of sick bed and its monitoring method for being used to monitor patient |
| CN108387610A (en) * | 2018-01-19 | 2018-08-10 | 上海交通大学 | marker detection device and detection method |
| CN110501506A (en) * | 2018-07-05 | 2019-11-26 | 东莞东阳光医疗智能器件研发有限公司 | A kind of biosensor and its application |
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