CN203587550U - Electrochemical immuno-biosensor detection device - Google Patents
Electrochemical immuno-biosensor detection device Download PDFInfo
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- CN203587550U CN203587550U CN201320694047.3U CN201320694047U CN203587550U CN 203587550 U CN203587550 U CN 203587550U CN 201320694047 U CN201320694047 U CN 201320694047U CN 203587550 U CN203587550 U CN 203587550U
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Abstract
The utility model discloses an electrochemical immuno-biosensor detection device. The device comprises a sound energy transmission and electrochemical immunoreaction detection device part, and a control detection part, wherein the electrochemical immunoreaction detection device part comprises an ultrasonic transducer, ultrasonic coupled colloid, a sound focusing lens array integrated glass substrate, a replaceable electrochemical immunobiologic sensitive membrane substrate, a macromolecule gold membrane electrode substrate and a multi-channel weak electrical signal detection circuit; the control detection part comprises an ultrasonic sensor, a PID (Proportion Integration Differentiation) ultrasonic energy model control module, a weak electrical signal processing module, a data analysis and feedback control module, and an energy control model and immune electrochemical reaction system coefficient database. The electrochemical immuno-biosensor detection device is excellent in detection low limit, sensitivity, accuracy, repeatability and stability.
Description
Technical field
The utility model belongs to biosensor technology field, relates to a kind of electro-chemistry immunity biology sensor pick-up unit, specifically the electrochemical immunosensor pick-up unit based on sonochemistry principle.
Background technology
A kind of immune analysis method combining with Electrochemical Detection as a kind of immune analysis method, electro-chemistry immunity biology sensor is because its selectivity is good, analysis speed is fast, operate simple and easy, easily form the high sensitivity with electrochemical analysis, there is again the feature of the high selectivity of immunoassay and the testing tool of narrow spectrum, high performance price ratio, and just a large amount of medical treatment & health that is applied in, food security, the every field such as environmental monitoring.But in its application process, also there are some problems, such as the performances such as consistency problem, detectability, sensitivity and detection speed being had in the application of requirements at the higher level, show the restricted one side of performance.How to develop performance brilliance, otherness is little, and the electro-chemistry immunity biology sensor that consistance is high or detection system just become an extremely crucial focus theme in current research and development.In recent decades, immuno analytical method combines the characteristic such as sensitive and convenient of the technology such as specific recognition reaction between antibody-antigen and galvanochemistry, photochemistry, spectroscopy, surface acoustic wave, such as high selectivity and the high sensitivity to target analytes such as tumor markers, stigmata protein, heavy metal ion, organic toxicants, become one of important analysis means of the every field such as clinical, biological chemistry, environmental analysis.For the analyzing detecting methods such as radio immunoassay, enzyme-linked immunosorbent assay, fluoroimmunoassay and chemiluminometry, electro-chemistry immunity biology sensor detect have without radiocontamination, the suitable simple and flexible of required instrument, detectability is low, highly sensitive and dynamics range is wide and can be easy to the multiple different pattern advantage such as integrated neatly, together with detecting with based on chemiluminescent photochemistry immunity bio-sensing, become the important detection means with great development prospect and enjoy high praise.
Micro-flowing injection analytical approach not only have convenient and flexible operation, analysis speed fast, be easy to robotization and accuracy advantages of higher, and have the advantages that application surface is wide.Can be applied to out-phase immune response and also go for homogeneous phase immune response.Loaded down with trivial details with respect to some conventional method of analysis operation stepss, analysis time is longer, sample consumption is large, the problems such as cost of determination height, micro-flowing injection technology combines with immunoassay and electrochemical detection method and the micro-flowing injection immuno analytical method that grows up has been proved to be as a kind of strong determination method, and corresponding analysis and detecting instrument device has also been widely used in numerous key areas of environmental monitoring, Pharmaceutical Analysis, Food Inspection and clinical analysis.But because conventional immune response is limited to its strict demand to reaction conditions and reaction system, and affected the efficiency of reacting, caused analysis time and analytical performance still to become a major issue can not be ignored.How effectively to solve this major issue, namely when shortening analysis time as far as possible, guarantee and improve the major issue of analytical performance, become key character of the present utility model.And for the feature of different electro-chemistry immunity biological respinse systems, from the angle of entire system, consider, the observing and controlling parameter of chemical effect of ultrasound is combined and forms exercisable Quality Control procedural information with electro-chemistry immunity performance of biosensor parameter technology is also the important key feature that the utlity model has broad applicability.
It is good that electro-chemistry immunity biology sensor has selectivity, analysis speed is fast, operate simple and easyly, form testing tool and there is the features such as high performance price ratio, but the existing reaction efficiency problem of sensor solid phase surface has still restricted its application prospect more widely to a certain extent.From the angle of detection system integral body, consider so, introduce the problem that new method and technological means solve sensor solid phase surface immune response efficiency effectively and will further effectively promote the development of electro-chemistry immunity biosensor technology, expand range of application and the application degree of depth.
First in the zymoprotein of the antibody (antigen) on immunity biosensor solid phase carrier and catalytic reaction and detected liquid, between corresponding antigen (antibody), have two alternate energy barrier---Nernst layers, how overcoming this barrier restriction raising reaction efficiency is an important problem.Secondly even if crossed over collision or combination in the antibody/antigen generation effecting reaction yardstick of this energy barrier, yet exist the probability of certain non-specific binding, this phenomenon can be brought ground unrest and interference, causes the reduction of the performances such as detectability, sensitivity and repetition consistance.Therefore how to promote that non-specific binding changes to specific binding, and improve the efficiency changing, also will be one of major issue how improving immune response efficiency.
According to the principle of sonochemistry, in chemical reaction, ultrasonic energy brings two basic effects, the one, oscillation effect, the 2nd, energy dispersal effect.According to analysis to existing problem in immune response, find, can utilize compositions of these effect Promote immunities reactions of ultrasonic energy to pass through not the Nernst layer between co-phasal surface and effectively react.The effect of this effect is also confirmed by many experimental works.In addition, for the specific binding power between antibody/antigen, be far longer than nonspecific adhesion, ultrasonic effect also can be accelerated to realize non-specific binding to the transformation of specific binding, namely promotes to arrange in conjunction with the reselecting property of albumen configuration.By controlling ultrasonic energy intensity, reduce within the specific limits the impact of energy perturbation on specific binding, ensure the conversion rates of its effective specific binding.The effect of these effects promotes reaction rate by physics mode to a certain extent, increases specific immune response efficiency and in the level of system, improves the performances such as detection lower bound, sensitivity and repetition consistance that electro-chemistry immunity bio-sensing detects.
Summary of the invention
Ultrasonic radiation energy accelerates electro-chemistry immunity biological respinse, particularly take micro-flowing injection technology and electro-chemistry immunity biosensor technology as basic analysis determining method and the device forming towards immune biological respinse.The same with the solid phase surface effect of typical immunity biosensor, the solid phase surface of electro-chemistry immunity biology sensor also exists many-sided material impact to immune response, and in immune bio-sensing testing process, the restriction of the diffusional effect between antibody and antigen or other enzyme labeling things is one of them important negative effect factor.The existence of this factor not only affects and detects reaction velocity in analytic process, also affects the sensitivity embodying of result simultaneously, has finally limited and has detected the effect of analyzing.The utility model is for this major issue, work characteristics for electro-chemistry immunity biological sensing and detecting system, according to the principle of sonochemistry, introduced controlled ultrasonic energy radiation function, by the energy perturbation of sensor solid phase surface region appropriateness is improved to immunoreactive speed in immunity biosensor sensitive membrane, obtain the effect of homogeneous reaction, promote degree of depth immune response, improve sensitivity and consistent repeatability that electro-chemistry immunity bio-sensing detects.Quality control in immunity bio-sensing testing process is also a very important problem, and the controlled ultrasonic energy radiotechnology of introducing according to the principle of sonochemistry can become the basic technology content of Quality Control process.By combining closely with Quality Control process, can standard ground obtain necessary observing and controlling parameter and performance parameter and form relation information database.This information database is the key components that form whole controlled ultrasonic energy radiation electrochemistry immunity biosensor pick-up unit system.
Feature of the present utility model is from entire system level, ultrasonic energy radiation function and electro-chemistry immunity biology sensor detection analysis are combined, and in the level of entire system, in conjunction with micro-flowing injection technology, finally form the analytical approach that electrochemical immunosensor pick-up unit based on sonochemistry principle and electro-chemistry immunity biological respinse are measured, improve the performance index such as detection lower bound, sensitivity and repetition consistance that detect analytic system.And the feature for different electro-chemistry immunity biological respinse systems, in entire system level, the observing and controlling parameter of chemical effect of ultrasound is combined with the performance parameter of electro-chemistry immunity biosensor technology, and form exercisable Quality Control procedural information needing in order to application widely.These are important key features of the present utility model.
The purpose of this utility model is for the deficiencies in the prior art, and a kind of electro-chemistry immunity biology sensor pick-up unit is provided.
The utility model device comprises acoustic energy transmission and electro-chemistry immunity reaction checking device part, control test section.
Described electro-chemistry immunity reaction checking device part comprises transducer fixing base 110, acoustic energy damping vibration attenuation sheet 109, ultrasonic transducer 101, ultrasonic coupling colloid 102, the integrated glass substrate 103 of sound focusing lens arra, cynapse point silicone rubber O-ring 108, replaceable electro-chemistry immunity bio-sensing film substrate 104, macromolecule gold film electrode substrate 107, hyperchannel ultra-weak electronic signal testing circuit 106 from bottom to up successively;
By the integrated glass substrate 103 of sound focusing lens arra, cynapse point silicone rubber O-ring 108, macromolecule gold film electrode substrate 107, set gradually from bottom to up and form flow injection reaction tank/injection device;
High-frequency transducer 101 is placed between macromolecule ultrasonic coupling colloid 102 and acoustic energy damping vibration attenuation sheet 109, controls the radiation intensity of high-frequency transducer's 101 ultrasonic energies by PID ultrasonic energy mode control module 202.
The integrated glass substrate 103 of sound focusing lens arra has two passages as the import and export of Fluid Transport, and two passages are located at respectively the both sides of ultrasonic coupling colloid 102; Integrated glass substrate 103 upper surfaces of sound focusing lens arra have groove, for placing sonac 201.This groove and two passages form inverted U-shaped structure, make fluid flow to another passage from a passage.
At the integrated glass substrate of sound focusing lens arra 103 edges, be provided with cynapse point silicone rubber O-ring 108, for seal flow injection reaction pond/injection device, regulate the height of the flowing reactive chamber 105 of flow injection reaction tank/injection device, and form enclosed construction with macromolecule gold film electrode substrate 107.
The height of the flowing reactive chamber 105 of described flow injection reaction tank/injection device is 1～3mm.
The material of described macromolecule gold film electrode substrate 107 is polymetylmethacrylate or polydimethylsiloxane;
On macromolecule gold film electrode substrate 107, have the groove that a plurality of thickness is 2mm, for intercalation electrode, electrode and replaceable electro-chemistry immunity bio-sensing film substrate 104 surperficial conductings, collect electric signal by replaceable electro-chemistry immunity bio-sensing film substrate 104 and arrive hyperchannel ultra-weak electronic signal testing circuit 106 by electrodes transfer;
Described electrode is the micro-spacing three-electrode structure of binary channels;
Described replaceable electro-chemistry immunity bio-sensing film substrate 104 is by cross-linking method, to carry out electrode face finish by silane, glutaraldehyde or shitosan, forms basement membrane; Then immobilized antigen molecule (or antibody molecule) and catalyzing enzyme on basement membrane, wherein catalyzing enzyme reacts in order to catalytic oxidation-reduction, produces electroactive material and causes curent change, and the kind of conventional catalyzing enzyme is alkaline phosphatase, horseradish peroxidase etc.
Described control test section comprises sonac 201, PID ultrasonic energy mode control module 202, ultra-weak electronic signal processing module 203, data analysis and feedback control module 204, energy-controlled mode and immune electrochemical reaction system database 205;
PID ultrasonic energy mode control module 202 is as controlled processing unit, receive the ultrasonic energy signal of sonac 201 and the feedback signal of energy-controlled mode and immune electrochemical reaction system database 205, PID ultrasonic energy mode control module 202 drives ultrasonic transducer 101 to start mode of operation; Ultra-weak electronic signal processing module 203 receives the collection signal of hyperchannel ultra-weak electronic signal testing circuit 106, energy-controlled mode and immune electrochemical reaction system database 205 are by the signal of data analysis and feedback control module 204 analyzing and processing ultra-weak electronic signal processing modules 203, then the signal after identification is transmitted to PID ultrasonic energy mode control module 202, finally regulate the ultrasound emission pattern (frequency and intensity) of ultrasonic transducer 101.
Utilize said apparatus to carry out the analytical approach of electro-chemistry immunity biological respinse mensuration, specifically utilize controlled ultrasonic radiation energy to promote the micro-flowing injection electro-chemistry immunity biological detection analytical approach of electro-chemistry immunity reaction efficiency.
Step (1). regulate the field of radiational energy of ultrasonic transducer 101
Concave spherical surface size by sound lens on ultrasonic coupling colloid 102 is focused, and making focus is 1～2mm to the vertical range on replaceable electro-chemistry immunity bio-sensing film substrate 104 surfaces.
On described ultrasonic coupling colloid 102, the characteristic dimension of the concave spherical surface of sound lens is determined by the design parameters such as characteristic dimension of the flowing reactive chamber 105 of energy size, macromolecule gold film electrode substrate 107 materials and thickness and the flow injection reaction tank/injection device of ultrasonic frequency, focusing.
Overall principle is: 1. regulate ultrasonic transducer 101 intensity to make the interior solution to be measured in flowing reactive chamber 105 of flow injection reaction tank/injection device can produce the disturbance of machinery and temperature, promote diffusional effect, the energy barrier that overcomes reaction, has improved reaction efficiency; 2. be adjusted to suitable intensity, can promote that in solution to be measured, non-specific binding molecular separation between antibody/antigen is reset, and change to specific binding, make solution reaction to be measured abundant.
Step (2). carry out micro-flowing injection analysis
The flowing reactive chamber 105 that solution to be measured, current-carrying are injected into flow injection reaction tank/injection device through a passage constant speed reaches the mixing of the two, finally through another passage, flows out.
In carrying out micro-flowing injection analytic process, if be fixed with antigen molecule on replaceable electro-chemistry immunity bio-sensing film substrate 104, make the corresponding antibodies generation specific binding reaction in solution to be measured.
The microminiaturization of reaction tank has been realized in the flowing reactive chamber 105 of described flow injection reaction tank/injection device by photoetching or etching method.
Step (3). ultrasound emission energy intelligent monitoring process
In carrying out the process of step (2), the utility model carries out ultrasound emission energy intelligent monitoring simultaneously.Described Based Intelligent Control process comprises two feedback signal path, is respectively feedback signal path, the detection feedback network of ultrasonic energy.
The feedback signal of described ultrasonic energy is detected the intensity of ultrasonic radiation energy by sonac 201, itself and ultrasonic transducer 101 and PID ultrasonic energy mode control module 202 form a closed loop measurement and control system.
PID ultrasonic energy mode control module 202 receives the ultrasonic energy signal of sonac 201, and PID ultrasonic energy mode control module 202 drives ultrasonic transducer 101 to start mode of operation.
Described detection feedback network is by PID ultrasonic energy mode control module 202, ultra-weak electronic signal, to process detection module 203, data analysis and feedback control module 204, energy-controlled mode and immune electrochemical reaction system database 205 to form closed loop measurement and control system.
Ultra-weak electronic signal is processed detection module 203 and is processed the electrochemical signals that hyperchannel ultra-weak electronic signal testing circuit 106 obtains, by ultrasonic energy mode control module 202, regulate the emittance of ultrasonic transducer to determine preferably immune response effect, data analysis and feedback control module 204 will be integrated the parameter sets of different immune response systems, forming energy control model and immune electrochemical reaction system database 205, the content of these databases provides necessary pid control parameter by the application for different immune detection analysis systems.Further, utilize the measured ultrasonic energy feedback parameter of standard Quality Control immune response solution and sonac 201, the dynamic effect of the control parameter that obtains ultrasonic radiation energy to electro-chemistry immunity reaction, by dynamics data between reaction effect parameter and ultrasonic energy control parameter is carried out to matching, obtain the Optimal Parameters for controlling, these Optimal Parameters and pid control parameter carry out information fusion, obtain the concentration of target antibody in solution to be measured or antigen.
Described intelligent monitoring method, according to the feature kinetic curve of the standard electric chemical reaction intensity obtaining in advance, obtains the control parameter of ultrasonic radiation energy, controls electro-chemistry immunity reaction.
The beneficial effects of the utility model are:
Based on sonochemistry principle, in the level of entire system, in conjunction with micro-flowing injection technology, integrate and control test section and cross-linking type electro-chemistry immunity biology sensor, provide a kind of brand-new controlled physics radiation energy that utilizes to promote electro-chemistry immunity reaction efficiency, improve the performance index such as detection lower bound, sensitivity and repetition consistance that detect analytic system.And the feature for different electro-chemistry immunity biological respinse systems, in entire system level, the observing and controlling parameter of chemical effect of ultrasound is combined with the performance parameter of electro-chemistry immunity biosensor technology, and form exercisable Quality Control procedural information needing in order to application widely.The higher level that makes it to be successfully adapted to the every field such as clinical, biological chemistry, environmental analysis detects analyzes requirement.
A) superior consistent reappearance.Sample and micro-stirring and reaction energy transmission effects that each stage of reacting of sensitive materials produces near reaction surface because ultrasonic energy focuses on, make the homogenising of reaction interface obtain larger lifting, guaranteed preferably consistent reappearance.
B) accelerate response sample and real reaction process, greatly shortened the reaction time, improved detection efficiency, be very suitable for the on-line quick detection application in a plurality of fields such as clinical, environmental monitoring, food security.
C) utilize crosslinked immobilized antigen, antibody molecule or the catalyzing enzymes such as silane, glutaraldehyde, shitosan, there is consumables cost low, the features such as technology maturation.
The utility model shows superior detection lower bound, sensitivity, accuracy, repeatability and stability, and preparation method is ripe simple, is conducive to develop into the product that has a market actual application value and promotes.
Figure of description
Fig. 1 is the structural representation of the utility model device;
Fig. 2 is the A-A cross-section separation structure schematic diagram of the utility model device;
Fig. 3 is the B-B cross-section separation structure schematic diagram of the utility model device.
Embodiment
Below in conjunction with accompanying drawing, the utility model is further analyzed.
As shown in Figure 1, Figure 2, Figure 3 shows, the utility model device comprises acoustic energy transmission and electro-chemistry immunity reaction checking device part, control test section to embodiment 1..
Electro-chemistry immunity reaction checking device part comprises transducer fixing base 110, acoustic energy damping vibration attenuation sheet 109, ultrasonic transducer 101, ultrasonic coupling colloid 102, the integrated glass substrate 103 of sound focusing lens arra, cynapse point silicone rubber O-ring 108, replaceable electro-chemistry immunity bio-sensing film substrate 104, macromolecule gold film electrode substrate 107, hyperchannel ultra-weak electronic signal testing circuit 106 from bottom to up successively;
By the integrated glass substrate 103 of sound focusing lens arra, cynapse point silicone rubber O-ring 108, macromolecule gold film electrode substrate 107, set gradually from bottom to up and form flow injection reaction tank/injection device;
High-frequency transducer 101 is placed between macromolecule ultrasonic coupling colloid 102 and acoustic energy damping vibration attenuation sheet 109, controls the radiation intensity of high-frequency transducer's 101 ultrasonic energies by PID ultrasonic energy mode control module 202.
The integrated glass substrate 103 of sound focusing lens arra has two passages as the import and export of Fluid Transport, and two passages are located at respectively the both sides of ultrasonic coupling colloid 102; Integrated glass substrate 103 upper surfaces of sound focusing lens arra have groove, for placing sonac 201.This groove and two passages form inverted U-shaped structure, make fluid flow to another passage from a passage.
At the integrated glass substrate of sound focusing lens arra 103 edges, be provided with cynapse point silicone rubber O-ring 108, for seal flow injection reaction pond/injection device, regulate the height of the flowing reactive chamber 105 of flow injection reaction tank/injection device, and form enclosed construction with macromolecule gold film electrode substrate 107.
The height of the flowing reactive chamber 105 of described flow injection reaction tank/injection device is 1～3mm.
The material of described macromolecule gold film electrode substrate 107 is polymetylmethacrylate or polydimethylsiloxane;
On macromolecule gold film electrode substrate 107, have the groove that a plurality of thickness is 2mm, for intercalation electrode, electrode and replaceable electro-chemistry immunity bio-sensing film substrate 104 surperficial conductings, collect electric signal by replaceable electro-chemistry immunity bio-sensing film substrate 104 and arrive hyperchannel ultra-weak electronic signal testing circuit 106 by electrodes transfer;
Described electrode is the micro-spacing three-electrode structure of binary channels;
Described replaceable electro-chemistry immunity bio-sensing film substrate 104 is by cross-linking method, to carry out electrode face finish by silane, glutaraldehyde or shitosan, forms basement membrane; Then immobilized antigen molecule (or antibody molecule) and catalyzing enzyme on basement membrane, wherein catalyzing enzyme reacts in order to catalytic oxidation-reduction, produces electroactive material and causes curent change, and the kind of conventional catalyzing enzyme is alkaline phosphatase, horseradish peroxidase etc.
Described control test section comprises sonac 201, PID ultrasonic energy mode control module 202, ultra-weak electronic signal processing module 203, data analysis and feedback control module 204, energy-controlled mode and immune electrochemical reaction system database 205;
PID ultrasonic energy mode control module 202 is as controlled processing unit, receive the ultrasonic energy signal of sonac 201 and the feedback signal of energy-controlled mode and immune electrochemical reaction system database 205, PID ultrasonic energy mode control module 202 drives ultrasonic transducer 101 to start mode of operation; Ultra-weak electronic signal processing module 203 receives the collection signal of hyperchannel ultra-weak electronic signal testing circuit 106, energy-controlled mode and immune electrochemical reaction system database 205 are by the signal of data analysis and feedback control module 204 analyzing and processing ultra-weak electronic signal processing modules 203, then the signal after identification is transmitted to PID ultrasonic energy mode control module 202, finally regulate the ultrasound emission pattern (frequency and intensity) of ultrasonic transducer 101.
The analytical approach that 2. 1 kinds of electro-chemistry immunity biological respinses of embodiment are measured, specifically utilizes controlled ultrasonic radiation energy to promote the micro-flowing injection electro-chemistry immunity biological detection analytical approach of electro-chemistry immunity reaction efficiency.
Step (1). regulate the field of radiational energy of ultrasonic transducer 101
Concave spherical surface size by sound lens on ultrasonic coupling colloid 102 is focused, and making focus is 1～2mm to the vertical range on replaceable electro-chemistry immunity bio-sensing film substrate 104 surfaces.
On described ultrasonic coupling colloid 102, the characteristic dimension of the concave spherical surface of sound lens is determined by the design parameters such as characteristic dimension of the flowing reactive chamber 105 of energy size, macromolecule gold film electrode substrate 107 materials and thickness and the flow injection reaction tank/injection device of ultrasonic frequency, focusing.
Overall principle is: 1. regulate ultrasonic transducer 101 intensity to make the interior solution to be measured in flowing reactive chamber 105 of flow injection reaction tank/injection device can produce the disturbance of machinery and temperature, promote diffusional effect, the energy barrier that overcomes reaction, has improved reaction efficiency; 2. be adjusted to suitable intensity, can promote that in solution to be measured, non-specific binding molecular separation between antibody/antigen is reset, and change to specific binding, make solution reaction to be measured abundant.
Step (2). carry out micro-flowing injection analysis
The flowing reactive chamber 105 that solution to be measured, current-carrying are injected into flow injection reaction tank/injection device through a passage constant speed reaches the mixing of the two, finally through another passage, flows out.
In carrying out micro-flowing injection analytic process, if be fixed with antigen molecule on replaceable electro-chemistry immunity bio-sensing film substrate 104, make the corresponding antibodies generation specific binding reaction in solution to be measured.
The microminiaturization of reaction tank has been realized in the flowing reactive chamber 105 of described flow injection reaction tank/injection device by photoetching or etching method.
Step (3). ultrasound emission energy intelligent monitoring process
In carrying out the process of step (2), the utility model carries out ultrasound emission energy intelligent monitoring simultaneously.Described Based Intelligent Control process comprises two feedback signal path, is respectively feedback signal path, the detection feedback network of ultrasonic energy.
The feedback signal of described ultrasonic energy is detected the intensity of ultrasonic radiation energy by sonac 201, itself and ultrasonic transducer 101 and PID ultrasonic energy mode control module 202 form a closed loop measurement and control system.
PID ultrasonic energy mode control module 202 receives the ultrasonic energy signal of sonac 201, and PID ultrasonic energy mode control module 202 drives ultrasonic transducer 101 to start mode of operation.
Described detection feedback network is by PID ultrasonic energy mode control module 202, ultra-weak electronic signal, to process detection module 203, data analysis and feedback control module 204, energy-controlled mode and immune electrochemical reaction system database 205 to form closed loop measurement and control system.
Ultra-weak electronic signal is processed detection module 203 and is processed the electrochemical signals that hyperchannel ultra-weak electronic signal testing circuit 106 obtains, by ultrasonic energy mode control module 202, regulate the emittance of ultrasonic transducer to determine preferably immune response effect, data analysis and feedback control module 204 will be integrated the parameter sets of different immune response systems, forming energy control model and immune electrochemical reaction system database 205, the content of these databases provides necessary pid control parameter by the application for different immune detection analysis systems.Further, utilize the measured ultrasonic energy feedback parameter of standard Quality Control immune response solution and sonac 201, the dynamic effect of the control parameter that obtains ultrasonic radiation energy to electro-chemistry immunity reaction, by dynamics data between reaction effect parameter and ultrasonic energy control parameter is carried out to matching, obtain the Optimal Parameters for controlling, these Optimal Parameters and pid control parameter carry out information fusion, obtain the concentration of target antibody in solution to be measured or antigen.
Described intelligent monitoring method, according to the feature kinetic curve of the standard electric chemical reaction intensity obtaining in advance, obtains the control parameter of ultrasonic radiation energy, controls electro-chemistry immunity reaction.
The typical preparation flow of the replaceable electro-chemistry immunity bio-sensing of embodiment 3. film substrate 104: 1. determined antigen is dissolved in to buffer solution, selected buffer solution is different because of antigen type, and principle is to make immunoreactive activity and chemiluminescence signal response reach maximum.2. to sensor carrier surface carry out pre-service obtain smooth, clean, hydrophilic surface.3. configure finite concentration epoxypropane base trimethyl silane solution, place and it was fully hydrolyzed in 60 minutes, then pipette 50 microlitre solution and drip in carrier surface, about 90 ℃ heating 60 minutes.Drip on the slide that 50 microlitre 1% chitosan-acetic acid solutions processed in GPS silanization, then be placed in baking oven to heat under the condition of 105 ℃ 60 minutes, obtain crosslinked with silicane glutaraldehyde basement membrane.4. 50 microlitre antigenic solutions are dripped on crosslinked with silicane glutaraldehyde (shitosan) basement membrane, in 4 ℃ of refrigerators, slowly volatilize 8 hours.5. with 50 microlitre bovine serum albumin solutions, drip on (4) step gained basement membrane, sealing active site, obtains immunologic function film.There are three aspects in the principal element that 6. affects institute's adaptive immune biological function basement membrane and immunosensor performance: (a) time enough and suitable temperature make the abundant hydrolysis reaction of epoxypropane base trimethyl silane; (b) preparation of immunity biosensor is subject to the impact of crosslinked glutaraldehyde (shitosan) surface topography, this depends primarily on the consumption of epoxypropane base trimethyl silane and glutaraldehyde (shitosan) in preparation process, only have consumption proportion suitable, could obtain rule, evenly, high conformity, present the crosslinked basement membrane of mesh-like structure, thereby it is high to prepare stability, the immunologic function film that performance is good; (c) the pH value of buffer solution: only, under certain acidity, antigen just has optimum activity.If acidity departs from this numerical value, the performance of immunologic function basement membrane and sensor will be affected.
The mensuration of embodiment 4. determined antigens: (1) is for different immune response systems such as the reaction of out-phase enzyme labeling electro-chemistry immunity, the non-enzyme labeling electro-chemistry immunity reaction of out-phase, the reaction of homogeneous phase enzyme labeling electro-chemistry immunity, the reactions of the non-enzyme labeling electro-chemistry immunity of out-phase, the optimal conditions of determining immunoassays is the effective active that guarantees antibody, antigen and marker enzyme, and electroactive reactive conditions.(2) for different immune response systems such as the reaction of out-phase enzyme labeling electro-chemistry immunity, the non-enzyme labeling electro-chemistry immunity reaction of out-phase, the reaction of homogeneous phase enzyme labeling electro-chemistry immunity, the reactions of the non-enzyme labeling electro-chemistry immunity of out-phase, determine different, but typical micro-flowing injection mode and flow process are injected electro-chemistry immunity reaction tank separately, detected solution is carried out to Electrochemical Detection analysis.According to the typical curve of measuring in Quality Control process, analyze identification, by the mode of multiparameter information fusion, obtain the concentration of target antibody/antigen in sample.
Claims (1)
1. an electro-chemistry immunity biology sensor pick-up unit, is characterized in that comprising acoustic energy transmission and electro-chemistry immunity reaction checking device part, control test section;
Described electro-chemistry immunity reaction checking device part comprises transducer fixing base 110, acoustic energy damping vibration attenuation sheet 109, ultrasonic transducer 101, ultrasonic coupling colloid 102, the integrated glass substrate 103 of sound focusing lens arra, cynapse point silicone rubber O-ring 108, replaceable electro-chemistry immunity bio-sensing film substrate 104, macromolecule gold film electrode substrate 107, hyperchannel ultra-weak electronic signal testing circuit 106 from bottom to up successively;
By the integrated glass substrate 103 of sound focusing lens arra, cynapse point silicone rubber O-ring 108, macromolecule gold film electrode substrate 107, set gradually from bottom to up and form flow injection reaction tank/injection device;
High-frequency transducer 101 is placed between macromolecule ultrasonic coupling colloid 102 and acoustic energy damping vibration attenuation sheet 109, controls the radiation intensity of high-frequency transducer's 101 ultrasonic energies by PID ultrasonic energy mode control module 202;
Ultrasonic coupling colloid 102 consists of ultrasonic coupling agent and macromolecule membrane; Wherein the acoustic impedance characteristic of macromolecule membrane and the acoustic impedance characteristic close of selected ultrasonic coupling agent;
Ultrasonic coupling colloid 102 upper surfaces are provided with acoustic lens array, and for focused ultrasound energy, ultrasonic coupling colloid 102 is close to by acoustic lens array and the integrated glass substrate 103 of sound focusing lens arra; The concave spherical surface size of sound lens is determined by focal length, and focal length is that lens surface is to the distance of the focus of supersonic beam focusing; By adjusting the concave spherical surface size of sound lens, control focus is 1～2mm to the vertical range on replaceable electro-chemistry immunity bio-sensing film substrate 104 surfaces;
The integrated glass substrate 103 of sound focusing lens arra has two passages as the import and export of Fluid Transport, and two passages are located at respectively the both sides of ultrasonic coupling colloid 102; Integrated glass substrate 103 upper surfaces of sound focusing lens arra have groove, for placing sonac 201; This groove and two passages form inverted U-shaped structure, make fluid flow to another passage from a passage;
At the integrated glass substrate of sound focusing lens arra 103 edges, be provided with cynapse point silicone rubber O-ring 108, for seal flow injection reaction pond/injection device, regulate the height of the flowing reactive chamber 105 of flow injection reaction tank/injection device, and form enclosed construction with macromolecule gold film electrode substrate 107;
The height of the flowing reactive chamber 105 of described flow injection reaction tank/injection device is 1～3mm;
On macromolecule gold film electrode substrate 107, have the groove that a plurality of thickness is 2mm, for intercalation electrode, electrode and replaceable electro-chemistry immunity bio-sensing film substrate 104 surperficial conductings, collect electric signal by replaceable electro-chemistry immunity bio-sensing film substrate 104 and arrive hyperchannel ultra-weak electronic signal testing circuit 106 by electrodes transfer;
Described electrode is the micro-spacing three-electrode structure of binary channels;
Described replaceable electro-chemistry immunity bio-sensing film substrate 104 is by cross-linking method, to carry out electrode face finish by silane, glutaraldehyde or shitosan, forms basement membrane; Then immobilized antigen molecule or antibody molecule and catalyzing enzyme on basement membrane;
Described control test section comprises sonac 201, PID ultrasonic energy mode control module 202, ultra-weak electronic signal processing module 203, data analysis and feedback control module 204, energy-controlled mode and immune electrochemical reaction system database 205;
PID ultrasonic energy mode control module 202 is as controlled processing unit, receive the ultrasonic energy signal of sonac 201 and the feedback signal of energy-controlled mode and immune electrochemical reaction system database 205, PID ultrasonic energy mode control module 202 drives ultrasonic transducer 101 to start mode of operation; Ultra-weak electronic signal processing module 203 receives the collection signal of hyperchannel ultra-weak electronic signal testing circuit 106, energy-controlled mode and immune electrochemical reaction system database 205 are by the signal of data analysis and feedback control module 204 analyzing and processing ultra-weak electronic signal processing modules 203, then the signal after identification is transmitted to PID ultrasonic energy mode control module 202, finally regulate the ultrasound emission pattern of ultrasonic transducer 101.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105092648A (en) * | 2015-08-28 | 2015-11-25 | 山东大学 | Tooth tattoo biosensor device for oral sanitation examination |
| CN105259320A (en) * | 2015-11-30 | 2016-01-20 | 中山市捷信科技服务有限公司 | Biosensor dividing device |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105092648A (en) * | 2015-08-28 | 2015-11-25 | 山东大学 | Tooth tattoo biosensor device for oral sanitation examination |
| CN105259320A (en) * | 2015-11-30 | 2016-01-20 | 中山市捷信科技服务有限公司 | Biosensor dividing device |
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