CN105372435A - Biological detection system based on graphene and making and integrating methods thereof - Google Patents
Biological detection system based on graphene and making and integrating methods thereof Download PDFInfo
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Abstract
The invention provides a high-sensitivity biological detection system based on graphene and making and integrating methods thereof. A high-sensitivity biosensor based on graphene is manufactured based on a silicon wafer firstly, then a conditioning circuit is designed to conduct amplification filtering on a signal output by the biosensor, data are converted and transmitted to a single-chip microcomputer through an A/D conversion chip, detected data are processed with the statistical method, a set of related disease factor risk assessment system is made, a liquid crystal display screen is added to display the disease risk level, and finally a micro-fluid channel is controlled through a driving circuit. The biological detection system made with the method can be used for detecting different types of disease related factors such as DNA, RNA and protein, viruses or cells and has the advantages of being high in sensitivity, stable, easy to integrate and the like.
Description
Technical field
The present invention relates to a kind of biological detection system based on Graphene, and make the method for the integrated highly sensitive biological detection system based on Graphene, be specifically related to a kind of method making integrated highly sensitive nano-device and measuring system.
Background technology
At present, diabetes, cardiovascular disease, breathing problem, hepatopathy, cancer are the major diseases threatening human health.Although medical science and related discipline make constant progress, people still make slow progress on the fast diagnosis and treatment of these diseases; If these diseases can not be found timely, be almost be difficult to treatment when disease arrives late period.And the reason that disease can not be found early is, one, time early stage, it is not obvious that related diseases sends out feature, and the associated protein of its secretion is relatively few because of quantum count, is not easy to detect by current detection means; Its two, namely enablely detect relevant disease factor, the expense needed for it and time are also many; Therefore, develop and a kind of there is high sensitivity, fast and the system of the detection relevant disease of low cost, to the diagnosis and treatment of the major disease of harm humans health, there is far reaching significance.
The most of biological detection equipment existed at present is the equipment based on electrochemical principle, or based on optical principle, also there is some devices based on field effect transistor FET or equipment, even there are some field effect FET device based on nanometer technology or equipment, even also this several mode combined the equipment of formation.The Technical comparing of electrochemistry detecting apparatus is ripe, but compares, and require higher, and volume is also relatively large to solution environmental.And present biology sensor mainly detects for a kind of single target molecule, due to a lot of with the molecule of any one disease association, and they may be separate; Therefore, a kind of existence of disease to be detected more accurately, joint-detection must be carried out to the various diseases factor.Patent CN101144809A utilizes argent as surface plasma excimer, and chemical group in its finishing also connects antigen molecule, by strengthening the intensity of local surface plasma resonance, improves the sensitivity of biomolecule detection.Patent CN1585896A utilizes FET sensor to detect ion concentration and base sequence, because charged ion or base sequence exist debye wavelength in the solution, if therefore ion and base sequence from conducting channel relatively away from time, its sensitivity detected also sharply declines.
Summary of the invention
The object of the invention is the deficiency overcoming prior art existence, a kind of making integrated approach of highly sensitive biological detection system is provided.
Object of the present invention is achieved through the following technical solutions:
The object of the present invention is to provide a kind of biological detection system based on Graphene, it comprises, based on the biology sensor of Graphene, modulate circuit, A/D conversion chip, driving circuit and the display part for the risk class that shows relevant disease; Described modulate circuit carries out amplification process to this sensor output signal; Described A/D conversion chip and driving circuit realize the transmission of data and the control of microfluidic channel.
Biological detection system of the present invention, the described biology sensor based on Graphene comprises, Graphene sensing unit and microfluidic channel.
Biological detection system of the present invention, described modulate circuit comprises pre-amplification circuit, low-pass filter circuit, main amplifier circuit and trap circuit.
Biological detection system of the present invention, described A/D conversion chip is connected with single-chip microcomputer, builds data transmission channel; Choose driving circuit, adopt chip L298N constructing system driving circuit, driving circuit is connected with single-chip microcomputer; Judge the magnitude relationship between solution concentration and definite value, and switch control rule is realized to microfluidic channel module.
Biological detection system of the present invention, the display part of the risk class of described display relevant disease is LCD MODULE.
Biological detection system of the present invention, described Graphene sensing unit is selected from Graphene resistance type sensor, graphene field effect sensor or Graphene electrochemica biological sensor.
Biological detection system of the present invention, utilizes dimethyl silicone polymer to produce described microfluidic channel, and carries out modification to the Graphene in microfluidic channel, makes it to modify upper different detection antibody or Small molecular, to detect different target molecules.
Biological detection system of the present invention, described Graphene sensing unit comprises: as substrate oxidized silicon chip, cover the metal electrode at Graphene on it and Graphene two ends.
Biological detection system of the present invention, described pre-amplification circuit adopts the three amplifier measuring and amplifying circuit of LM725CN with automatic offset compensation, and increase has a corrective network; Described low-pass filter circuit is made up of double operational integrated circuit OP2177; Described main amplifying circuit will be divided into front and back stages, connect the input/output terminal with 50Hz trapper respectively; Described trap circuit adopts integrated transporting discharging double T feedback frequency-selecting amplifier filtering part to enter the Hz noise of circuit in differential mode mode.
The present invention also provides a kind of making integrated approach of the biological detection system based on Graphene, comprise the following steps: the integrated step of making of biology sensor, build modulate circuit to this sensor output signal carry out amplification filtering process step, utilize A/D conversion chip and driving circuit realize the step of the transmission of data and the control of microfluidic channel module and utilize statistical method to analyze experimental data, and set up the step that a set of disease risks judges system.
The present invention another based on the biology sensor of Graphene, comprise, Graphene sensing unit and microfluidic channel, modified modified being connected with of the Graphene in described microfluidic channel detects antibody or Small molecular.
Biology sensor based on Graphene of the present invention, described Graphene width between 1-10000 nanometer, thickness is between 0.5-5 nanometer.
Biology sensor based on Graphene of the present invention, described modification is via the chemical group being selected from allylamine, 11-bromo Kui Ji trichlorosilane, 2-carbonylethyl trichlorosilane, octyltrichlorosilane, 9-enylcarbamate butyl ester, ammonia propyl trichlorosilane.
Biology sensor based on Graphene of the present invention, described detection antibody or Small molecular are selected from DNA, RNA, protein, virus or cell.
Biology sensor based on Graphene of the present invention, the quantity of described microfluidic channel is at 1-200.
The present invention further provides a kind of preparation method of the biology sensor based on Graphene, the method comprises the following steps: the preparation process of Graphene sensing unit and the preparation process of microfluidic channel, and modified modified being connected with of the Graphene in described microfluidic channel detects antibody or Small molecular.
The preparation method of the biology sensor based on Graphene of the present invention, the method also comprises protein-bonded step.
The preparation method of the biology sensor based on Graphene of the present invention, described detection antibody or Small molecular are selected from cardiac troponin label corresponding antibodies, immunoglobulin (Ig), neural stem cell.
The technical scheme that the present invention relates to, its outstanding substantive distinguishing features and significant progress are mainly reflected in the following aspects.The making of the biological detection system based on Graphene that the present invention relates to and integrated approach, PDMS and insulating material is adopted to make microfluidic channel, Graphene in passage is modified, make it possible to dissimilar biomolecule be detected, by the information of these biomolecule is carried out Conjoint Analysis, can detect disease more accurately.Meanwhile, adopt Graphene as the core material detected, can combine with semiconductor technology, and solve lithography alignment problem, the precision of element manufacturing can be improved, reduce bad ratio defective product, thus reduce chip cost.And have employed passivation layer to protect device, avoid the infiltration of hydrone, electric current etc. in next step reaction, extend system lifetim.In addition have employed single-chip microcomputer and the intellectuality that switch control rule achieves detection has been carried out to microfluidic channel.The detection system that the method makes can be used for detecting the dissimilar disease association factor (as DNA, RNA, protein etc.) simultaneously, virus or cell, has high sensitivity, stablizes, is easy to the advantage such as integrated.
Accompanying drawing explanation
Fig. 1 is present system overall plan block diagram;
Fig. 2 is device profile map after surface passivation in field effect type sensor production of the present invention;
Fig. 3 is that the present invention has made sensor construction sectional view after field effect type sensor microfluidic channel;
Fig. 4 is field effect type sensor surface of the present invention modification, the sensor construction sectional view in modification after detection molecules;
Fig. 5 is three amplifier measuring and amplifying circuit of the automatic offset compensation of band built for sensor output signal;
Fig. 6 is the filtering circuit of signal after elementary three amplifier amplifying circuits;
Fig. 7 is that A/D conversion chip carries out conversion process to data and transfers to single chip circuit figure;
Fig. 8 is that microfluidic channel controls driving circuit;
Fig. 9 is the relation matching distribution plan obtained after Data Analysis Services;
Figure 10 shows for utilizing liquid crystal display to be connected with single-chip microcomputer to realize risk result of determination;
Figure 11 is the process flow diagram based on biological detection system of the present invention.
In figure, the implication of Reference numeral is as follows: the drain electrode of 1 silicon substrate, 2 substrate silicon dioxide, 3 top layer silicon, 4FET fet gate, 5FET field effect transistor source electrode, 6FET field effect transistor, 7 Graphenes, 8 silicon nitride passivation protective seams, 9 dimethyl silicone polymers, 10 antibody, 11 microfluidic channel, 12 antibody recognition unit.
Embodiment
The invention provides a kind of making and integrated approach of high-sensitive biological and chemical detection system.By the high-sensitive biosensor of silicon wafer to manufacture based on Graphene; Then design modulate circuit to amplify this sensor output signal; Then utilize A/D conversion chip carry out conversion process to data and transfer to single-chip microcomputer, thus realize the display detecting data; Finally, driving circuit is utilized to control microfluidic channel.The biological detection system made in this way can be used for detecting the dissimilar disease association factor (as DNA, RNA, protein etc.), virus or cell, has high sensitivity, stablizes, is easy to the feature such as integrated.Meanwhile, this manufacture method is mutually compatible with conventional semiconductor processing, can carry out large-scale production, be convenient to reduce costs.
Be compared to traditional checkout equipment, biological detection system based on Graphene has following advantage: one, high sensitivity, first in sensor, field effect transistor inherently has the effect of signal amplification, can amplify acting on a small amount of charge signal got on; Secondly, due to the large specific surface area that Graphene itself has, fractional quantum hall effect etc., make the field effect FET sensor based on Graphene have very high sensitivity; Two, quick, the speed based on the semi-conductor chip of silicon can reach the frequency of GHz, and even may reach higher speed based on the field effect FET sensor of Graphene, and this compares with traditional checkout equipment, and its detection speed quickly; Three, be easy to integrated detect with high flux, compare with checkout equipment with traditional sensors, detection system based on Graphene has advantage that is easy of integration and low cost, because the manufacturing process of period is completely mutually compatible with semiconductor technology, the industries such as therefore easy and ripe semi-conductor industry and emerging MEMS are compatible, thus can obtain the sensor of feature richness, superior performance.Silicon is very abundant at the content of occurring in nature, and meanwhile, existing semi-conductor industry technology can reduce the cost of device.
Object of the present invention is achieved through the following technical solutions:
Based on the making integrated approach of the highly sensitive biological detection system of Graphene, comprise the following steps:
(1) based on the high-sensitive biosensor of silicon wafer to manufacture based on Graphene;
(2) build modulate circuit and amplification filtering process is carried out to this sensor output signal;
(3) A/D conversion chip and driving circuit is utilized to realize the transmission of data and the control of microfluidic channel;
(4) utilize statistical method to analyze experimental data, and set up a set of disease risks judgement system, can judge risk factor, and add the risk class of Liquid Crystal Module display relevant disease.
Further, the making integrated approach of the above-mentioned highly sensitive biological detection system based on Graphene, step () comprises following operation:
Make the high-sensitive biosensor based on Graphene, first based on silicon wafer to manufacture Graphene FET field effect transistor, then dimethyl silicone polymer is utilized to produce microfluidic channel, finally modification is carried out to the Graphene in microfluidic channel, make it to modify upper different detection antibody or Small molecular, to detect different target molecules.Specifically comprise following step:
Semiconductor processing method is adopted to make Graphene sensing unit based on silicon chip.First at silicon dioxide or the silicon nitride film of grown above silicon one deck 20 ~ 200 nanometer thickness, then obtained back electrode on silicon chip, transfers on silicon chip by Graphene, by deep UV (ultraviolet light) carving method then, obtain graphene conductive raceway groove through etching, and make metal electrode at Graphene two ends.
Dimethyl silicone polymer is utilized to produce microfluidic module.First utilize photoetching method to make on silicon chip and obtain Microflow module mould, then PDMS performed polymer to be poured on microchannel mould and to place and within 24 hours, make it to be polymerized completely, obtain microfluidic channel module through the demoulding.Then the Graphene sensing unit silicon chip that will complete carries out with microfluidic channel module aiming at, bonding.
Modification is carried out to the Graphene in microfluidic channel, makes it to modify upper different detection antibody or Small molecular to detect different target molecules.First silicon chip is placed in the glutaraldehyde phosphate buffer mixed liquor of 1:15 and within one hour, carries out surface aldehydes shaking bed reaction, then combine the corresponding antibodies of upper material to be detected, finally clean up with buffer solution.
Further, the making integrated approach of the above-mentioned highly sensitive biological detection system based on Graphene, step (two) comprises following operation:
First, signal for sensor output builds the pre-amplification circuit of coupling, adopt the three amplifier measuring and amplifying circuit of LM725CN with automatic offset compensation, as the pre-amplifier of this amplifying circuit, the instrument amplifier of this form, its input impedance is about 30-5000M Ω, common-mode rejection ratio (CMR) R
db=74 ~ 110dB, input offset voltage V
os=0.2mV, offset voltage temperature drift r=0.25 ~ 10 μ V/ DEG C.A corrective network is added in three amplifiers, amplifier A4 and resistance R, electric capacity C form an integrator, its effect be by the dc component of amplifier A3 output terminal through integration, anti-phase after feed back to its in-phase input end, deduct from input signal, thus eliminate the impact of offset voltage.
Subsequently, build low-pass filter circuit, be made up of double operational integrated circuit OP2177.For not losing its radio-frequency component, by Frequency Design be:
Then, building main amplifier circuit, for avoiding distorted signals, just main amplifying circuit being divided into front and back stages, connect the input/output terminal with 50Hz trapper respectively, and the gain amplifier of each 100 times is provided.
Finally, design and build 50Hz trap circuit, adopting integrated transporting discharging double T feedback frequency-selecting amplifier filtering part to enter the Hz noise of circuit in differential mode mode.
Further, the making integrated approach of the above-mentioned highly sensitive biological detection system based on Graphene, step (three) comprises following operation:
Choose suitable A/D conversion chip to be connected with single-chip microcomputer, build attenuator circuit with a slice AD8056 chip, after decay, select high-speed AD 9280 chip to realize the conversion of data, and A/D chip is connected with 8051 single-chip microcomputers, build data transmission channel.
Choose driving circuit, adopt chip L298N constructing system driving circuit, driving circuit is connected with single-chip microcomputer;
Coding realizes the transmission of data to single-chip microcomputer, and when there being signal to input, program just carries out the magnitude relationship judged between solution concentration and definite value.If gained voltage is greater than this definite value, then make P1.0=0, open microfluidic channel; Otherwise, then make P1.0=1, close microfluidic channel, thus realize the switch control rule to microfluidic channel.
Further, the making integrated approach of the above-mentioned highly sensitive biological detection system based on Graphene, step (four) comprises following operation:
Target molecule to be measured is utilized to configure concentration known gradient solution;
Measure the electrical signal of gradient solution respective sensor conversion, set up corresponding relation;
Utilize statistical method, set up responsive diseases risk based on this corresponding relation and judge system;
Tested sample solution is injected the microfluidic channel of biology sensor, measure the electrical signal of sensor conversion;
Utilize measuring-signal, judge system with reference to disease wind direction, and then the degree of risk of this sample is judged;
Add LCD MODULE, above-mentioned judged result " safety ", " warning " or " danger " are presented on liquid crystal display.Wherein, " safety " uses yellow representative with green representative, " warning ", and " danger " represents with red.First to carry out initialization to liquid crystal display, i.e. cls.Then to its write character, and then risk judgment result is shown on this liquid crystal display.
Below in conjunction with accompanying drawing, technical solution of the present invention is described further:
Sensor construction as shown in Figure 4; be made up of silicon substrate 1, substrate silicon dioxide 2 and Graphene 3 three; and comprise metal source 5, drain electrode 6, grid 4 and silicon nitride passivation protective seam 8, dimethyl silicone polymer (PDMS) 9, and the microfluidic channel 11 formed.Sensor is made based on Graphene.Graphene width is between 1-10000 nanometer, and thickness is between 0.5-5 nanometer.
Add isopropyl alcohol (IPA) in described corrosive liquid, the concentration of IPA is 0%-50%.The method for making of graphene conductive raceway groove is obtained by the physics such as ion beam etching (IBE), reactive ion beam etching (RIBE) (RIE), dark silicon inductively coupled plasma etching (dark silicon ICP) or chemical etching method.The material of silicon nitride passivation protective seam 8 is silicon nitride film, silica membrane, spin-coating glass (comprise PSG; BPSG), silicon dioxide (fluorinated silica is improved; HSQ), BN, Si; can also be organic, comprise polyimide, hatching polyimide, Fluoro-aggregation, Si-O-C polyblend etc.The method such as CVD, PECVD or LPCVD, SOD, sputtering can be used to grow.Passivation layer covers other places outside sensor surface Graphene and metal electrode.Film protection sensor surface, and form microfluidic channel.Microfluidic channel 11 is formed together by silicon nitride passivation protective seam 8 and poly dimethyl oxygen alkane (PDMS) 9, and the quantity of microfluidic channel, between 1-200, carries out the reaction vessel of chemical modification and target detection during microfluidic channel module.The chemical group 14 that specificity is modified can be: allylamine, 11-bromo Kui Ji trichlorosilane (11-bromoundecyltrichlorosilane, BUTCS), 2-carbonylethyl trichlorosilane (2-(carbomethoxy) ethyltrichlorosilane, CMECS), octyltrichlorosilane (n-octyltrichlorosilane, OTCS), 9-enylcarbamate butyl ester (dec-9-enyl-carbamicacidtert-butylester, CAE), ammonia propyl trichlorosilane (3-aminopropyltriethoxylsilane, APTES).Antibody 10 is different in different microfluidic channel 11, and detect biomolecule (as DNA, RNA, protein etc.) accordingly, antibody recognition unit (12) is also different.The input of sensor is drawn in microchannel by target molecule damping fluid to be detected by microflow channels with peristaltic pump, and being combined in the opposite sex on corresponding antibody molecule.Which results in the change of sensor conductance.Thus change chemical signal into electric signal and detected by peripheral testing circuit.Containing a reference channel in each sensor, this passage unmodified chemical group and antibody.The microfluidic channel of each detection should have one to contrast passage mutually, the corresponding buffer solution for not containing detection target molecule flow through in passage.
Embodiment Ι
Based on the making integrated approach of the highly sensitive cardiac troponin detection system of Graphene, comprise the following steps:
(1) based on the highly sensitive cardiac troponin sensor of silicon wafer to manufacture based on Graphene
1) Wafer Cleaning, silicon chip is respectively at the concentrated sulphuric acid and the hydrogen peroxide of 7:3, and the ammoniacal liquor of 1:3:7 and aqueous hydrogen peroxide solution, in the hydrochloric acid of 1:2:8 and aqueous hydrogen peroxide solution, heat 10-15 minute at 60 DEG C, removes the organism contained by silicon chip surface and metallic ion;
2) etching mask growth, adopts a kind of method be selected from PECVD, LPCVD, plasma sputtering or method for oxidation, at silicon dioxide or the silicon nitride film of grown above silicon one deck 20-200 nano thickness;
3) back electrode makes, and first by the method for back electrode by deep-UV lithography, then by dry etching, silicon chip makes and obtains back electrode pattern;
4) Graphene transfer, transfers on silicon chip by Graphene in water;
5) graphene-channel makes, and first uses Graphene masterplate by the method for deep-UV lithography, then obtains width in 1-10000 nanometer by etching, the graphene conductive raceway groove that homogeneity is good;
6) metallize, first by the method for metallization masterplate by deep-UV lithography, then the method by peeling off, make Graphene two end electrodes and the metallization of silicon back electrode, complete Graphene sensing unit and make;
7) microfluidic channel makes, and first utilizes the method for photoetching to make on silicon chip and obtains microfluidic channel mould;
8) build model, PDMS performed polymer is poured on microfluidic channel mould, and place 24 hours, make it to be polymerized completely;
9) shift, the PDMS be polymerized has been transferred on the wafer of Graphene sensing unit making, aimed at, bonding;
10) surface aldehydes, is placed on glutaraldehyde phosphate buffer (PBS) the mixed liquor reaction of 1:15, (30mlPBS by wafer, 2ml glutaraldehyde, PBS is phosphate buffer PH=7.2), shaking bed reaction one hour, making Graphene aldehyde radical in microfluidic channel;
11) associated proteins, in conjunction with upper cardiac troponin label corresponding antibodies;
12) clean, react complete, clean 3 times with buffer solution, often all over 5 minutes, often 2 minutes, time interval.
(2) build modulate circuit and amplification filtering process is carried out to this sensor output signal
13) first, signal for sensor output builds the pre-amplification circuit of coupling, adopt the three amplifier measuring and amplifying circuit of LM725CN with automatic offset compensation, as the pre-amplifier of this amplifying circuit, the instrument amplifier of this form, its input impedance is about 30-5000M Ω, common-mode rejection ratio (CMR) R
db=74 ~ 110dB, input offset voltage V
os=0.2mV, offset voltage temperature drift r=0.25 ~ 10 μ V/ DEG C.A corrective network is added in three amplifiers, amplifier A4 and resistance R, electric capacity C form an integrator, its effect be by the dc component of amplifier A3 output terminal through integration, anti-phase after feed back to its in-phase input end, deduct from input signal, thus eliminate the impact of offset voltage.
14) subsequently, build low-pass filter circuit, be made up of double operational integrated circuit OP2177.For not losing its radio-frequency component, by Frequency Design be:
15) then, building main amplifier circuit, for avoiding distorted signals, just main amplifying circuit being divided into front and back stages, connect the input/output terminal with 50Hz trapper respectively, and the gain amplifier of each 100 times is provided.
16) last, design and build 50Hz trap circuit, adopting integrated transporting discharging double T feedback frequency-selecting amplifier filtering part to enter the Hz noise of circuit in differential mode mode.
(3) A/D conversion chip and driving circuit is utilized to realize the transmission of data and the control of microfluidic channel
17) choose suitable A/D conversion chip to be connected with single-chip microcomputer, build attenuator circuit with a slice AD8056 chip, after decay, select high-speed AD 9280 chip to realize the conversion of data, and A/D chip is connected with 8051 single-chip microcomputers, build data transmission channel.
18) choose driving circuit, adopt chip L298N constructing system driving circuit, driving circuit is connected with single-chip microcomputer;
19) coding realizes the transmission of data to single-chip microcomputer, and when there being signal to input, program just carries out the magnitude relationship judged between solution concentration and definite value.If gained voltage is greater than this definite value, then make P1.0=0, open microfluidic channel; Otherwise, then make P1.0=1, close microfluidic channel, thus realize the switch control rule to microfluidic channel.
(4) utilize statistical method to analyze experimental data, and set up a set of disease risks judgement system, can judge risk factor
20) with target molecule configuration concentration known gradient solution to be measured;
21) measure the electrical signal of gradient solution respective sensor conversion, set up corresponding relation;
22) utilize statistical method, set up responsive diseases risk based on this corresponding relation and judge system;
23) cardiac troponin concentration and electrical quantities is utilized | Δ I
t/ I
0| between corresponding relation set up risk judge system, when recording cardiac troponin concentration at 0 ~ 1ng/ml, thinking and being in safe class; When recording cardiac troponin concentration at 1 ~ 6ng/ml, thinking to be in needs danger classes; When recording cardiac troponin concentration higher than 6ng/ml, thinking and being in high-risk grade, and then realize the judgement to the risk of myocardial infarction;
Add LCD MODULE, above-mentioned judged result " safety ", " danger " or " high-risk " are presented on liquid crystal display.Wherein, " safety " uses yellow representative with green representative, " danger ", and " high-risk " represents with red.First initialization to be carried out to liquid crystal display, i.e. cls.Then to its write character, and then risk judgment result is shown on this liquid crystal display.
The present invention is based on making and the integrated approach of the biological detection system of Graphene, PDMS and insulating material is adopted to make microfluidic channel, Graphene in passage is modified, make it possible to dissimilar biomolecule be detected, by the information of these biomolecule is carried out Conjoint Analysis, can detect disease more accurately.Meanwhile, adopt Graphene as the core material detected, can combine with conventional semiconductor processing, and solve lithography alignment problem, the precision of element manufacturing can be improved, reduce bad ratio defective product, thus reduce chip cost.And have employed passivation layer to protect device, avoid the infiltration of hydrone, electric current etc. in next step reaction, extend system lifetim.In addition have employed single-chip microcomputer and the intellectuality that switch control rule achieves detection has been carried out to microfluidic channel.The detection system that the method makes can be used for detecting the dissimilar disease association factor (as DNA, RNA, protein etc.) simultaneously, virus or cell, has high sensitivity, stablizes, is easy to the advantage such as integrated.
Claims (18)
1. based on a biological detection system for Graphene, it is characterized in that: comprise, based on the biology sensor of Graphene, modulate circuit, A/D conversion chip, driving circuit and the display part for the risk class that shows relevant disease; Described modulate circuit carries out amplification process to this sensor output signal; Described A/D conversion chip and driving circuit realize the transmission of data and the control of microfluidic channel.
2. biological detection system according to claim 1, is characterized in that: the described biology sensor based on Graphene comprises, Graphene sensing unit and microfluidic channel.
3. biological detection system according to claim 1, is characterized in that: described modulate circuit comprises pre-amplification circuit, low-pass filter circuit, main amplifier circuit and trap circuit.
4. biological detection system according to claim 1, is characterized in that: described A/D conversion chip is connected with single-chip microcomputer, builds data transmission channel; Choose driving circuit, adopt chip L298N constructing system driving circuit, driving circuit is connected with single-chip microcomputer; Judge the magnitude relationship between solution concentration and definite value, and switch control rule is realized to microfluidic channel module.
5. biological detection system according to claim 1, is characterized in that: the display part of the risk class of described display relevant disease is LCD MODULE.
6. biological detection system according to claim 2, is characterized in that: described Graphene sensing unit is selected from Graphene resistance type sensor, graphene field effect sensor or Graphene electrochemica biological sensor.
7. biological detection system according to claim 2, it is characterized in that: utilize dimethyl silicone polymer to produce described microfluidic channel, and modification is carried out to the Graphene in microfluidic channel, makes it to modify upper different detection antibody or Small molecular, to detect different target molecules.
8. biological detection system according to claim 6, is characterized in that: described Graphene sensing unit comprises: as substrate oxidized silicon chip, cover the metal electrode at Graphene on it and Graphene two ends.
9. biological detection system according to claim 6, is characterized in that: described pre-amplification circuit adopts the three amplifier measuring and amplifying circuit of LM725CN with automatic offset compensation, and increase has a corrective network; Described low-pass filter circuit is made up of double operational integrated circuit OP2177; Described main amplifying circuit will be divided into front and back stages, connect the input/output terminal with 50Hz trapper respectively; Described trap circuit adopts integrated transporting discharging double T feedback frequency-selecting amplifier filtering part to enter the Hz noise of circuit in differential mode mode.
10. the making integrated approach based on the biological detection system of Graphene, it is characterized in that, comprise the following steps: the integrated step of making of biology sensor, build modulate circuit to this sensor output signal carry out amplification filtering process step, utilize A/D conversion chip and driving circuit realize the step of the transmission of data and the control of microfluidic channel module and utilize statistical method to analyze experimental data, and set up the step that a set of disease risks judges system.
11. 1 kinds, based on the biology sensor of Graphene, is characterized in that: comprise, Graphene sensing unit and microfluidic channel, and modified modified being connected with of the Graphene in described microfluidic channel detects antibody or Small molecular.
12. biology sensors based on Graphene according to claim 11, is characterized in that: described Graphene width between 1-10000 nanometer, thickness is between 0.5-5 nanometer.
13. biology sensors based on Graphene according to claim 11, is characterized in that: described modification is via the chemical group being selected from allylamine, 11-bromo Kui Ji trichlorosilane, 2-carbonylethyl trichlorosilane, octyltrichlorosilane, 9-enylcarbamate butyl ester, ammonia propyl trichlorosilane.
14. biology sensors based on Graphene according to claim 11, is characterized in that: described detection antibody or Small molecular are selected from DNA, RNA, protein, virus or cell.
15. biology sensors based on Graphene according to claim 11, is characterized in that: the quantity of described microfluidic channel is at 1-200.
16. 1 kinds of preparation methods based on the biology sensor of Graphene, the method comprises the following steps: the preparation process of Graphene sensing unit and the preparation process of microfluidic channel, and modified modified being connected with of the Graphene in described microfluidic channel detects antibody or Small molecular.
The preparation method of 17. biology sensors based on Graphene according to claim 16, the method also comprises protein-bonded step.
The preparation method of 18. biology sensors based on Graphene according to claim 16, described detection antibody or Small molecular are selected from cardiac troponin label corresponding antibodies, immunoglobulin (Ig), neural stem cell.
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| CN106290541A (en) * | 2016-08-03 | 2017-01-04 | 天津喜诺生物医药有限公司 | Quickly detect graphene sensor and the preparation method of gram negative bacteria lipopolysaccharide |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106290541A (en) * | 2016-08-03 | 2017-01-04 | 天津喜诺生物医药有限公司 | Quickly detect graphene sensor and the preparation method of gram negative bacteria lipopolysaccharide |
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| CN109431538A (en) * | 2018-11-24 | 2019-03-08 | 广西中医药大学附属瑞康医院 | A kind of gene tester and equipment applied to supersonic imaging apparatus |
| CN110184184A (en) * | 2019-05-07 | 2019-08-30 | 宁波大学 | A kind of preparation method and applications integrating nucleic acid extraction, enrichment and the nucleic acid reaction device in situ expanded |
| CN110184184B (en) * | 2019-05-07 | 2022-03-11 | 浙江正合谷生物科技有限公司 | Preparation method and application of nucleic acid reactor integrating nucleic acid extraction, enrichment and in-situ amplification |
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