CN105372435B - Biological detection system and its making integrated approach based on graphene - Google Patents

Biological detection system and its making integrated approach based on graphene Download PDF

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CN105372435B
CN105372435B CN201410422781.3A CN201410422781A CN105372435B CN 105372435 B CN105372435 B CN 105372435B CN 201410422781 A CN201410422781 A CN 201410422781A CN 105372435 B CN105372435 B CN 105372435B
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graphene
circuit
detection system
biological detection
microfluidic channel
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CN105372435A (en
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杨赢
苏瑞巩
***
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Suzhou Institute of Nano Tech and Nano Bionics of CAS
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Suzhou Institute of Nano Tech and Nano Bionics of CAS
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Abstract

The present invention provides a kind of highly sensitive biological detection system based on graphene, and it makes integrated approach, it is primarily based on high-sensitive biosensor of the silicon wafer to manufacture based on graphene, then design modulate circuit is amplified filtering to the sensor output signal, then data are changed using A/D conversion chips and transmitted to single-chip microcomputer, then the data that detection obtains are handled using statistical method and formulates the risk judgement system of a set of relevant disease factor, then LCDs is added so as to realize the display of disease risks grade, finally microfluidic channel is controlled using drive circuit.The biological detection system that this method makes can be used for detecting different types of disease correlation factor (such as DNA, RNA, protein), virus or cell, have the characteristics that high sensitivity, stably, be easily integrated.

Description

Biological detection system and its making integrated approach based on graphene
Technical field
The present invention relates to a kind of biological detection system based on graphene, and make integrated based on the highly sensitive of graphene A kind of method of biological detection system, and in particular to method for making integrated highly sensitive nano-device and measuring system.
Background technology
At present, diabetes, cardiovascular disease, breathing problem, hepatopathy, cancer are to threaten the great disease of human health Disease.Although medical science and related discipline make constant progress, people still make slow progress on the fast diagnosis and treatment of these diseases;This Almost it is difficult treatment if a little diseases can not timely be found, when disease reaches late period.And disease can not obtain and Early the reason for finding, is that first, during early stage, related diseases send out feature unobvious, and the GAP-associated protein GAP factor quantity that it is secreted is relative It is less, it is not easy to detect with current detection means;Second, the i.e. enabled disease factor for detecting correlation, needed for it Expense and time are also more;Therefore, develop a kind of with high sensitivity, quick and inexpensive detection relevant disease System, there is far reaching significance to endangering the diagnosis and treatment of major disease of human health.
The most of biological detection equipment currently existed is the equipment based on electrochemical principle, or former based on optics Reason, there is also some devices or equipment based on FET FET, or even has some field-effect FET based on nanometer technology Device or equipment, or even this several ways is also combined into the equipment to be formed.The Technical comparing of electrochemistry detecting apparatus is ripe, But compare, to solution environmental require it is higher, and volume also compare it is larger.And present biology sensor is main It is to be detected for a kind of single target molecule, because the molecule related to any disease is a lot, and they can Can be separate;Therefore, a kind of presence of disease is more accurately detected, it is necessary to which a variety of disease factors are combined Detection.Patent CN101144809A is by the use of argent as surface plasma excimer, and chemical group is simultaneously in its surface modification Antigen molecule in connection, by strengthening the intensity of local surface plasma resonance, to improve the sensitivity of biomolecule detection. Patent CN1585896A is to detect ion concentration and base sequence using FET sensor, due to charged ion or base sequence Row debye wavelength in the solution be present, so if ion and base sequence from conducting channel relatively far away from when, its detect spirit Sensitivity also drastically declines.
The content of the invention
The purpose of the present invention is to overcome the shortcomings of the prior art, there is provided a kind of making of highly sensitive biological detection system Integrated approach.
The purpose of the present invention is achieved through the following technical solutions:
It is an object of the invention to provide a kind of biological detection system based on graphene, it includes, based on graphene The display of biology sensor, modulate circuit, A/D conversion chips, drive circuit and the risk class for showing relevant disease Portion;The modulate circuit is amplified processing to the sensor output signal;The A/D conversion chips realize number with drive circuit According to transmission and microfluidic channel control.
Biological detection system of the present invention, the biology sensor based on graphene include, and graphene sensing is single Member and microfluidic channel.
Biological detection system of the present invention, the modulate circuit include pre-amplification circuit, low-pass filter circuit, master Amplifier circuit and trap circuit.
Biological detection system of the present invention, the A/D conversion chips are connected with single-chip microcomputer, and structure data transfer is led to Road;Drive circuit is chosen, using chip L298N constructing system drive circuits, drive circuit is connected with single-chip microcomputer;Judge solution Magnitude relationship between concentration and definite value, and switch control is realized to microfluidic channel module.
Biological detection system of the present invention, the display part of the risk class of the display relevant disease is liquid crystal display Module.
Biological detection system of the present invention, the graphene sensing unit are selected from graphene resistance type sensor, stone Black alkene field effect transistor or graphene electrochemica biological sensor.
Biological detection system of the present invention, the microfluidic channel is produced using dimethyl silicone polymer, and Modification is carried out to the graphene in microfluidic channel, the upper different detection antibody of modification or small molecule are allowed to, to detect not Same target molecule.
Biological detection system of the present invention, the graphene sensing unit include:Oxidized silicon chip as substrate, cover Cover graphene thereon and the metal electrode at graphene both ends.
Biological detection system of the present invention, the pre-amplification circuit is using LM725CN with automatic offset compensation Three amplifier measuring and amplifying circuits, and increase has a compensation network;The low-pass filter circuit is by double operational integrated circuit OP2177 Form;The main amplifying circuit will be divided into front and back stages, respectively connection and the input/output terminal of 50Hz trappers;The trap electricity Road uses the double T feedbacks frequency-selective amplifiers of integrated transporting discharging to filter out the Hz noise that part enters circuit in a manner of differential mode.
The present invention also provides a kind of making integrated approach of the biological detection system based on graphene, comprises the following steps: The integrated step of making of biology sensor, build the step that modulate circuit is amplified filtering process to the sensor output signal Suddenly the step of transmission and the control of microfluidic channel module of data, are realized using A/D conversion chips and drive circuit, Yi Jili Experimental data is analyzed with statistical method, and establishes the step of a set of disease risks judge system.
Another biology sensor based on graphene of the invention, including, graphene sensing unit and microfluidic channel, Graphene in the microfluidic channel is connected with detection antibody or small molecule after modification.
Biology sensor of the present invention based on graphene, the graphene width is between 1-10000 nanometers, thickness Degree is between 0.5-5 nanometers.
Biology sensor of the present invention based on graphene, the modification is via selected from allylamine, 11- bromos Kui Ji Trichlorosilane, 2- carbonylethyls trichlorosilane, octyltrichlorosilane, 9- enylcarbamates butyl ester, ammonia propane base trichlorosilane Chemical group.
Biology sensor of the present invention based on graphene, the detection antibody or small molecule are selected from DNA, RNA, egg White matter, virus or cell.
Biology sensor of the present invention based on graphene, the quantity of the microfluidic channel is in 1-200.
The present invention further provides a kind of preparation method of the biology sensor based on graphene, this method includes following step Suddenly:The preparation process of graphene sensing unit and the preparation process of microfluidic channel, the graphene in the microfluidic channel Detection antibody or small molecule are connected with after modification.
The preparation method of biology sensor of the present invention based on graphene, this method also include protein-bonded step Suddenly.
The preparation method of biology sensor of the present invention based on graphene, the detection antibody or small molecule are selected from Cardiac troponin label corresponding antibodies, immunoglobulin, NSC.
Technical scheme of the present invention, its substantive distinguishing features protruded and significant progress are mainly reflected in following Aspect.The making of biological detection system of the present invention based on graphene and integrated approach, using PDMS and insulation material Expect, to make microfluidic channel, to modify the graphene in passage, enabling different types of biomolecule is detected, By the way that the information of these biomolecule is carried out into Conjoint Analysis, more accurately disease can be detected.Meanwhile using graphite Core material of the alkene as detection, can be combined, and solve the problems, such as lithography alignment, it is possible to increase device with semiconductor technology The precision that part makes, bad products rate is reduced, so as to reduce chip cost.And passivation layer is employed to protect device, The infiltration of hydrone, electric current etc. in reacting in next step is avoided, extends system lifetim.In addition single-chip microcomputer is employed to microfluid Passage, which has carried out switch control, realizes the intellectuality of detection.The detecting system that this method makes can be used for detecting difference simultaneously The disease correlation factor (such as DNA, RNA, protein) of type, virus or cell, have high sensitivity, stably, be easy to collect Into the advantages that.
Brief description of the drawings
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 profile after field effect type sensor microfluidic channel;
Fig. 4 is that field effect type sensor surface of the present invention is modified, the sensor construction section in modification after detection molecules Figure;
Fig. 5 is three amplifier measuring and amplifying circuits of the automatic offset compensation of band built for sensor output signal;
Fig. 6 is filter circuit of the signal after primary three amplifier amplifying circuits;
Fig. 7 is that A/D conversion chips carry out conversion process to data and transmitted to single chip circuit figure;
Fig. 8 is that microfluidic channel controls drive circuit;
Fig. 9 is fitted distribution map for the relation obtained after Data Analysis Services;
Figure 10 realizes that risk result of determination is shown to be connected using liquid crystal display with single-chip microcomputer;
Figure 11 is the flow chart of the biological detection system based on the present invention.
In figure, the implication of reference is as follows:1 silicon substrate, 2 substrate silica, 3 top layer silicons, 4FET FET grid Pole, 5FET FETs source electrode, 6FET FET drains, 7 graphenes, 8 silicon nitride passivation protective layers, 9 polydimethylsiloxanes Alkane, 10 antibody, 11 microfluidic channels, 12 antibody recognition units.
Embodiment
The present invention provides making and the integrated approach of a kind of highly sensitive biological and chemical detecting system.Pass through silicon wafer to manufacture High-sensitive biosensor based on graphene;Then design modulate circuit is amplified to the sensor output signal;Then Conversion process is carried out to data using A/D conversion chips and transmitted to single-chip microcomputer, so as to realize the display of detection data;Finally, Microfluidic channel is controlled using drive circuit.The biological detection system made in this way can be used for detecting difference The disease correlation factor (such as DNA, RNA, protein) of type, virus or cell, have high sensitivity, stably, be easily integrated The features such as.Meanwhile this manufacture method is mutually compatible with conventional semiconductor processing, can be mass produced, be easy to reduce into This.
Traditional detection device is compared to, the biological detection system based on graphene has following advantage:First, Gao Ling Field-effect transistor inherently has the function that signal amplification in sensitivity, first sensor, can be effect up a small amount of Charge signal is amplified;Secondly as graphene possessed big specific surface area, fractional quantum hall effect etc. in itself, So that the field-effect FET sensor based on graphene has very high sensitivity;2nd, it is quick, the semiconductor chip based on silicon Speed can reach GHz frequency, and the field-effect FET sensor based on graphene possibly even reaches higher speed, this Compared with traditional detection device, its detection speed is very fast;3rd, be easily integrated with high flux detect, with traditional sensors and Detection device is compared, and the detecting system based on graphene has advantage easy of integration and inexpensive, due to the making of period Journey is completely mutually compatible with semiconductor technology, therefore easily compatible with the semi-conductor industry and the industry such as emerging MEMS of maturation, So as to obtain feature-rich, superior performance sensor.Content of the silicon in nature is very abundant, meanwhile, it is existing Semi-conductor industry technology can reduce the cost of device.
The purpose of the present invention is achieved through the following technical solutions:
The making integrated approach of highly sensitive biological detection system based on graphene, comprises the following steps:
(1) based on high-sensitive biosensor of the silicon wafer to manufacture based on graphene;
(2) build modulate circuit and filtering process is amplified to the sensor output signal;
(3) transmission of data and the control of microfluidic channel are realized using A/D conversion chips and drive circuit;
(4) experimental data is analyzed using statistical method, and establishes a set of disease risks and judge system, can Risk factor is judged, and adds the risk class that Liquid Crystal Module shows relevant disease.
Further, the making integrated approach of the above-mentioned highly sensitive biological detection system based on graphene, step (1) Include following process:
The high-sensitive biosensor based on graphene is made, is primarily based on silicon wafer to manufacture graphene FET FETs, so Microfluidic channel is produced using dimethyl silicone polymer afterwards, modification finally is carried out to the graphene in microfluidic channel, The upper different detection antibody of modification or small molecule are allowed to, to detect different target molecules.Specifically include following steps:
Graphene sensing unit is made using semiconductor processing method based on silicon chip.First one layer 20 of grown above silicon~ The silica or silicon nitride film of 200 nanometer thickness, back electrode is then made on silicon chip, then transfers graphene to silicon chip On, it is etched to obtain graphene conductive raceway groove by DUV carving method, and make metal electrode at graphene both ends.
Microfluidic module is produced using dimethyl silicone polymer.Made first with photolithography method on silicon chip and obtain miniflow Module die, then PDMS performed polymers are poured on microchannel mould and placed and are allowed within 24 hours polymerize completely, obtained through the demoulding Microfluidic channel module.Then the graphene sensing unit silicon chip that will complete is aligned with microfluidic channel module, is bonded.
Modification is carried out to the graphene in microfluidic channel, be allowed to the upper different detection antibody of modification or small molecule with Detect different target molecules.Silicon chip is placed on 1 first:Bed reaction is being shaken in 15 glutaraldehyde phosphate buffer mixed liquor Carry out surface aldehydes within one hour, in conjunction with the corresponding antibodies of upper material to be detected, finally cleaned up with cushioning liquid.
Further, the making integrated approach of the above-mentioned highly sensitive biological detection system based on graphene, step (2) Include following process:
The pre-amplification circuit of matching is built firstly, for the signal of sensor output, using the automatic imbalance of LM725CN bands Three amplifier measuring and amplifying circuits of compensation, as the pre-amplifier of this amplifying circuit, the instrument amplifier of this form, its is defeated It is about 30-5000M Ω, common-mode rejection ratio (CMR) R to enter impedancedb=74~110dB, input offset voltage Vos=0.2mV, imbalance The μ V/ DEG C of voltage temperature drift r=0.25~10.A compensation network, amplifier A4 and resistance R, electric capacity C composition are added in three amplifiers One integrator, its act on be by the dc component of amplifier A3 output ends it is integrated, it is anti-phase after feed back to its in-phase input end, from Subtracted in input signal, so as to eliminate the influence of offset voltage.
Then, low-pass filter circuit is built, is made up of double operational integrated circuit OP2177.Not lose its radio-frequency component, It is by Frequency Design:
Then, main amplifier circuit is built, to avoid distorted signals, main amplifying circuit is just divided into front and back stages, respectively Connection and the input/output terminal of 50Hz trappers, and each 100 times of gain amplifier is provided.
Finally, design and build 50Hz trap circuits, use the double T feedbacks frequency-selective amplifiers of integrated transporting discharging to filter out part with difference Mould mode enters the Hz noise of circuit.
Further, the making integrated approach of the above-mentioned highly sensitive biological detection system based on graphene, step (3) Include following process:
Choose suitable A/D conversion chips with single-chip microcomputer to be connected, build attenuator circuit with a piece of AD8056 chips, decay it Afterwards, the conversion of data is realized from the chip of high-speed AD 9280, and A/D chips are connected with 8051 single-chip microcomputers, builds data transfer Passage.
Drive circuit is chosen, using chip L298N constructing system drive circuits, drive circuit is connected with single-chip microcomputer;
Write program and realize transmission of the data to single-chip microcomputer, when there is signal input, program just carries out judgement solution concentration Magnitude relationship between definite value.If gained voltage is more than the definite value, P1.0=0 is made, opens microfluidic channel;Conversely, then P1.0=1 is made, closes microfluidic channel, so as to realize the switch control to microfluidic channel.
Further, the making integrated approach of the above-mentioned highly sensitive biological detection system based on graphene, step (4) Include following process:
Concentration known gradient solution is configured using target molecule to be measured;
The electrical signal of gradient solution respective sensor conversion is measured, establishes corresponding relation;
Using statistical method, responsive diseases risk is established based on the corresponding relation and judges system;
By the microfluidic channel of tested sample solution injection biology sensor, the electrical signal that sensor is changed is measured;
Using measurement signal, system is judged with reference to disease wind direction, and then the degree of risk of the sample is judged;
LCD MODULE is added, above-mentioned judged result " safety ", " warning " or " danger " is shown on liquid crystal display.Its In, " safety " is represented with green, and " warning " is represented with yellow, and " danger " is represented with red.First liquid crystal display is initialized, That is cls.Then character is write to it, and then risk judgment result is shown on this liquid crystal display.
Technical solution of the present invention is described further below in conjunction with the accompanying drawings:
Sensor construction as shown in Figure 4, it is made up of silicon substrate 1, substrate silica 2 and the three of graphene 3, and Including metal source 5, drain electrode 6, grid 4 and silicon nitride passivation protective layer 8, dimethyl silicone polymer (PDMS) 9, and formed Microfluidic channel 11.Sensor is made based on graphene.Between 1-10000 nanometers, thickness exists graphene width Between 0.5-5 nanometers.
Isopropanol (IPA) is added in described corrosive liquid, IPA concentration is 0%-50%.The system of graphene conductive raceway groove It is by ion beam etching (IBE), reactive ion beam etching (RIBE) (RIE), deep silicon inductively coupled plasma etching (deep silicon as method ) etc. ICP physics or chemical etching method obtain.The material of silicon nitride passivation protective layer 8 is silicon nitride film, silica is thin Film, spin-coating glass (including PSG, BPSG), improvement silica (fluorinated silica, HSQ), BN, Si, can also be organic , including polyimides, hatching polyimides, Fluoro- aggregations, Si-O-C polyblends etc..CVD, PECVD can be used Or the methods of LPCVD, SOD, sputtering, grows.Passivation layer is covered in other ground outside sensor surface graphene and metal electrode Side.Film protects sensor surface, and forms microfluidic channel.Microfluidic channel 11 be by silicon nitride passivation protective layer 8 and Poly dimethyl oxygen alkane (PDMS) 9 is formed together, and the quantity of microfluidic channel is carried out between 1-200, during microfluidic channel module Chemical modification and the reaction vessel of target detection.Specifically the chemical group 14 of sex modification can be:Allylamine, 11- bromo Kuis Base trichlorosilane (11-bromoundecyltrichlorosilane, BUTCS), 2- carbonylethyl trichlorosilanes (2- (carbomethoxy) ethyltrichlorosilane, CMECS), octyltrichlorosilane (n- Octyltrichlorosilane, OTCS), 9- enylcarbamates butyl ester (dec-9-enyl-carbamicacid tert- Butylester, CAE), ammonia propane base trichlorosilane (3-aminopropyltriethoxylsilane, APTES).Antibody 10 It is different in different microfluidic channels 11, detects biomolecule (such as DNA, RNA, protein) accordingly, antibody is known Other unit (12) is also different.The signal detection of sensor is to be delayed target molecule to be detected by microflow channels with peristaltic pump Fliud flushing is drawn into microchannel, and being incorporated in the opposite sex on corresponding antibody molecule.Which results in changing for sensor conductance Become.So as to which chemical signal is changed into electric signal and come out by periphery detection electric circuit inspection.Contain one in each sensor Individual reference channel, the passage and unmodified chemical group and antibody.The microfluidic channel each detected should mutually have a contrast Passage, what is flowed through in passage is the corresponding cushioning liquid without detection target molecule.
Embodiment Ι
The making integrated approach of highly sensitive cardiac troponin detecting system based on graphene, comprises the following steps:
(1) based on highly sensitive cardiac troponin sensor of the silicon wafer to manufacture based on graphene
1) Wafer Cleaning, silicon chip is respectively 7:3 concentrated sulfuric acid and hydrogen peroxide, 1:3:7 ammoniacal liquor and aqueous hydrogen peroxide solution, 1: 2:In 8 hydrochloric acid and aqueous hydrogen peroxide solution, 10-15 minutes are heated at 60 DEG C, remove organic matter and gold contained by silicon chip surface Belong to ion;
2) etching mask grows, using one kind side in PECVD, LPCVD, plasma sputtering or method for oxidation Method, in the silica or silicon nitride film of one layer of 20-200 nano thickness of grown above silicon;
3) back electrode makes, the first method with back electrode by deep-UV lithography, then by dry etching, made on silicon chip Obtain back electrode pattern;
4) graphene shifts, and is transferred graphene in water on silicon chip;
5) graphene-channel makes, the first method with graphene masterplate by deep-UV lithography, then obtain width with etching In 1-10000 nanometers, the good graphene conductive raceway groove of homogeneity;
6) metallize, first with metallization method of the masterplate by deep-UV lithography, then the method by stripping, make graphene Two end electrodes and the metallization of silicon back electrode, complete graphene sensing unit and make;
7) microfluidic channel makes, and is made first with the method for photoetching on silicon chip and obtains microfluidic channel mould;
8) model is poured, PDMS performed polymers are poured on microfluidic channel mould, and is placed 24 hours, is allowed to gather completely Close;
9) shift, the PDMS having polymerize is transferred to and completed on the chip that graphene sensing unit makes, is aligned, bonding;
10) surface aldehydes, chip is placed on 1:15 glutaraldehyde phosphate buffer (PBS) mixed liquor reaction, (30mlPBS, 2ml glutaraldehyde, PBS are phosphate buffer PH=7.2), one hour of bed reaction is being shaken, is making microfluidic channel Middle graphene aldehyde radical;
11) associated proteins, with reference to upper cardiac troponin label corresponding antibodies;
12) clean, reaction finishes, clean 3 times with cushioning liquid, every all over 5 minutes, every all over being spaced 2 minutes.
(2) build modulate circuit and filtering process is amplified to the sensor output signal
13) signal firstly, for sensor output builds the pre-amplification circuit of matching, automatic using LM725CN bands Three amplifier measuring and amplifying circuits of 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) Rdb=74~110dB, input offset voltage Vos=0.2mV, The μ V/ DEG C of offset voltage temperature drift r=0.25~10.A compensation network, amplifier A4 and resistance R, electric capacity C are added in three amplifiers Form an integrator, its act on be by the dc component of amplifier A3 output ends it is integrated, it is anti-phase after feed back to its homophase input End, is subtracted from input signal, so as to eliminate the influence of offset voltage.
14) low-pass filter circuit then, is built, is made up of double operational integrated circuit OP2177.For do not lose its high frequency into Point, it is by Frequency Design:
15) main amplifier circuit then, is built, to avoid distorted signals, main amplifying circuit is just divided into front and back stages, point And each 100 times of gain amplifier Lian Jie not be provided with the input/output terminal of 50Hz trappers.
16) finally, design and build 50Hz trap circuits, part is filtered out using the double T feedbacks frequency-selective amplifiers of integrated transporting discharging Enter the Hz noise of circuit in a manner of differential mode.
(3) transmission of data and the control of microfluidic channel are realized using A/D conversion chips and drive circuit
17) suitable A/D conversion chips are chosen with single-chip microcomputer to be connected, builds attenuator circuit with a piece of AD8056 chips, decline After subtracting, the conversion of data is realized from the chip of high-speed AD 9280, and A/D chip is connected with 8051 single-chip microcomputers, structure data pass Defeated passage.
18) drive circuit is chosen, using chip L298N constructing system drive circuits, drive circuit is connected with single-chip microcomputer;
19) write program and realize transmission of the data to single-chip microcomputer, when there is signal input, program just carries out judging that solution is dense Magnitude relationship between degree and definite value.If gained voltage is more than the definite value, P1.0=0 is made, opens microfluidic channel;Conversely, P1.0=1 is then made, closes microfluidic channel, so as to realize the switch control to microfluidic channel.
(4) experimental data is analyzed using statistical method, and establishes a set of disease risks and judge system, can Risk factor is judged
20) concentration known gradient solution is configured with target molecule to be measured;
21) electrical signal of gradient solution respective sensor conversion is measured, establishes corresponding relation;
22) statistical method is utilized, establishing responsive diseases risk based on the corresponding relation judges system;
23) cardiac troponin concentration and electrical quantities are utilized | Δ It/I0| between corresponding relation establish risk judge body System, when measuring cardiac troponin concentration in 0~1ng/ml, it is believed that in safe class;It is dense when measuring cardiac troponin Degree is in 1~6ng/ml, it is believed that in needing danger classes;When measuring cardiac troponin concentration and being higher than 6ng/ml, it is believed that In high-risk grade, and then realize the judgement to the risk of myocardial infarction;
LCD MODULE is added, above-mentioned judged result " safety ", " danger " or " high-risk " is shown on liquid crystal display. Wherein, " safety " is represented with green, and " danger " is represented with yellow, and " high-risk " is represented with red.First have to carry out liquid crystal display Initialization, i.e. cls.Then character is write to it, and then risk judgment result is shown on this liquid crystal display.
The making of the biological detection system based on graphene of the invention and integrated approach, using PDMS and insulating materials come Microfluidic channel is made, the graphene in passage is modified, enabling detect different types of biomolecule, pass through The information of these biomolecule is subjected to Conjoint Analysis, more accurately disease can be detected.Meanwhile made using graphene For the core material of detection, can be combined with conventional semiconductor processing, and solve the problems, such as lithography alignment, it is possible to increase device The precision that part makes, bad products rate is reduced, so as to reduce chip cost.And passivation layer is employed to protect device, The infiltration of hydrone, electric current etc. in reacting in next step is avoided, extends system lifetim.In addition single-chip microcomputer is employed to microfluid Passage, which has carried out switch control, realizes the intellectuality of detection.The detecting system that this method makes can be used for detecting difference simultaneously The disease correlation factor (such as DNA, RNA, protein) of type, virus or cell, have high sensitivity, stably, be easy to collect Into the advantages that.

Claims (7)

  1. A kind of 1. biological detection system based on graphene, it is characterised in that:Including the biology sensor based on graphene, adjusting Manage the display part of circuit, A/D conversion chips, drive circuit and the risk class for showing relevant disease;The conditioning electricity Road is amplified processing to the sensor output signal;The A/D conversion chips and drive circuit realize the transmission of data with it is micro- The control of fluid passage;The modulate circuit includes pre-amplification circuit, low-pass filter circuit, main amplifier circuit and trap Circuit;The pre-amplification circuit uses three amplifier measuring and amplifying circuits of the LM725CN with automatic offset compensation, and increase has one Compensate network;The low-pass filter circuit is made up of double operational integrated circuit OP2177;The main amplifying circuit will be divided into front and rear Two-stage, the input/output terminal with 50Hz trappers is connected respectively;The trap circuit is using the double T feedbacks frequency-selecting amplifications of integrated transporting discharging Device filters out the Hz noise that part enters circuit in a manner of differential mode;The A/D conversion chips are connected with single-chip microcomputer, and structure data pass Defeated passage;The drive circuit uses chip L298N constructing system drive circuits, and drive circuit is connected with single-chip microcomputer;It is described Single-chip microcomputer realizes switch control to microfluidic channel module according to the magnitude relationship between solution concentration and definite value.
  2. 2. biological detection system according to claim 1, it is characterised in that:The biology sensor bag based on graphene Include, graphene sensing unit and microfluidic channel.
  3. 3. biological detection system according to claim 1, it is characterised in that:The risk class of the display relevant disease Display part is LCD MODULE.
  4. 4. biological detection system according to claim 2, it is characterised in that:The graphene sensing unit is selected from graphene Resistance type sensor, graphene field effect sensor or graphene electrochemica biological sensor.
  5. 5. biological detection system according to claim 2, it is characterised in that:Produced using dimethyl silicone polymer described Microfluidic channel, and modification is carried out to the graphene in microfluidic channel, be allowed to the upper different detection antibody of modification or Small molecule, to detect different target molecules.
  6. 6. biological detection system according to claim 4, it is characterised in that:The graphene sensing unit includes:As The oxidized silicon chip of substrate, cover graphene thereon and the metal electrode at graphene both ends.
  7. 7. a kind of making integrated approach of the biological detection system according to claim 1 based on graphene, its feature exist In comprising the following steps:The making of biology sensor integrates step, builds modulate circuit puts to the sensor output signal The step of big filtering process, using A/D conversion chips and drive circuit realize the transmission of data and the control of microfluidic channel module The step of processed and experimental data is analyzed using statistical method, and establishes cardiac troponin concentration and electrical quantities | ΔIt/I0| between corresponding relation.
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