CN103995050A - Surface acoustic wave glucose sensor and making method thereof - Google Patents
Surface acoustic wave glucose sensor and making method thereof Download PDFInfo
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- CN103995050A CN103995050A CN201410254858.0A CN201410254858A CN103995050A CN 103995050 A CN103995050 A CN 103995050A CN 201410254858 A CN201410254858 A CN 201410254858A CN 103995050 A CN103995050 A CN 103995050A
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Abstract
The invention discloses a surface acoustic wave glucose sensor and a making method thereof. The surface acoustic wave glucose sensor comprises a single-substrate dual-path surface acoustic wave sensor and a periphery differential circuit, wherein the single-substrate dual-path surface acoustic wave sensor is formed in a manner that two pairs of input and output transducers are simultaneously made on one substrate to form detection and reference sensors, a glucose oxidase which has high specificity to glucose is fixed between the input and output transducers of the detection sensor, and the reference sensor is mainly used for reducing errors caused by an outside environment. According to the surface acoustic wave glucose sensor, a piezoelectric material is used as a substrate, the surface acoustic wave sensor on the substrate comprises a delay line type and a resonance type. The periphery differential circuit is used for obtaining a comparison differential signal between the detection sensor and the reference signal; and the content of the glucose can be detected through quantitatively analyzing the differential signal. The surface acoustic wave glucose sensor has the advantages of small volume, simple making process, low cost and the like, and is easily integrated.
Description
Technical field
The present invention relates to a kind of glucose sensor, particularly a kind of surface acoustic wave glucose sensor and preparation method thereof.
Background technology
Glucose is organic main energy source, is also to form one of the most basic chemical substance of animals and plants organism.Therefore, building glucose sensor realization has very important significance in food industry, biological medicine and clinical medicine to the quantitative detection of glucose.Glucose sensor is to study one of the most extensive and commercial applications sensor the earliest, not only be widely used in the fields such as food, medical industry and environmental monitoring, also in clinical examination, blood sugar is monitored and had broad application prospects with sensitivity, particularly diabetes patient's blood sugar monitoring is played an important role.Diabetes are global frequently-occurring diseases, World Health Organization's survey report demonstration, and whole world diabetic has exceeded 3.47 hundred million, the serious threat mankind's health.Treating diabetes and clinical testing show, carrying out blood sugar test and insulin management timely is frequently the effective ways that prevent hypoglycemia and diabetic complication.Therefore, diabetes patient need regulate diet by repeatedly measuring blood sugar concentration every day, to reach the object of controlling blood sugar.Adopting more blood sugar test method is at present based on optics and galvanochemistry blood glucose sensor.Optics blood glucose sensor is generally to utilize near infrared light to measure a kind of sensor of glucose content, and its accuracy and sensitivity are lower, there is no at present the commercial applications example that detects blood sugar as accurate quantification.Galvanochemistry blood glucose sensor is the detection that realizes blood sugar by the electric signal in detection chemical reaction process, and its specificity is lower, is easily interfered.In addition, it is medical disposable material that most blood glucose sensors all need to adopt blood sugar test paper, blood sugar test paper, and price is more expensive.
Surface acoustic wave biology sensor is the class Novel Biosensor that development in recent years is got up, its principle of work is: on the travel path of SAW (Surface Acoustic Wave) resonator or lag line, be coated with the selective identification biological substance of one deck (as protein, DNA, pathogen, cell, virus etc.) sensitive membrane, form sensitizing range, in the time there is physisorption or chemical reaction in sensitizing range in test substance, the physical quantity such as mass loading or viscosity of sensitizing range will change, the surface acoustic wave parameter of device is (as acoustic surface wave speed, frequency, phase place, time delay etc.) also change thereupon, by detecting frequency drift, phase place changes or time delay just can detect test substance and content thereof.The surface acoustic wave biology sensor Measurement for Biotechnique traditional with other compared and had the advantages such as easy to detect, speed is fast, sensitivity is high.Chinese scholars mainly concentrates on the detection to following biological substance to the research of surface acoustic wave biology sensor, comprise and detect protein, bacterium, DNA, cell, hepatitis surface antibody (HBsAb), there is no at present the report that adopts surface acoustic wave biosensor technique to detect blood sugar.
The result of investigation is not also found the patent of surface acoustic wave glucose sensor at present.
Summary of the invention
The invention provides a kind of surface acoustic wave glucose sensor and preparation method thereof, can provide a kind of novel detection technique for the blood sugar test of glucose content detection and diabetes patient in food, medical industry, environmental monitoring.
The present invention relates to a kind of surface acoustic wave glucose sensor, comprise monocrepid two-way surface acoustic wave sensor and peripheral difference channel; Monocrepid two-way surface acoustic wave sensor is to make detecting sensor and reference sensor on a substrate simultaneously, between the input and output transducer of detecting sensor, apply glucose is had to specific glucose oxidase, reference sensor is in order to reduce non-specific adsorption, temperature variation, humidity variation, viscosity variation, and the phase place that causes of other biological composition or the impact of frequency drift, the record that detects data can adopt phase place or two kinds of detection schemes of frequency; Surface acoustic wave glucose sensor adopts piezoelectric as substrate, and piezoelectric is piezoelectricity block and piezoelectric membrane.Piezoelectricity block can be selected lithium niobate, lithium tantalate and quartz crystal, and the piezoelectric ceramics such as PZT, and piezoelectric membrane can be selected ZnO, AIN and PVDF film.On substrate, make two pairs of input and output transducers, form and detect and reference sensor; Described surface acoustic wave sensor comprises delay line type and mode of resonance surface acoustic wave sensor; Described peripheral difference channel, for obtaining the poor sub-signal between detecting sensor and reference sensor, just can detect glucose content by quantitative test differential signal.
The detection principle of surface acoustic wave glucose sensor is: the glucose oxidase that applies a layer-selective identification glucose molecule on the travel path of SAW (Surface Acoustic Wave) resonator or lag line, form surface acoustic wave glucose sensor, in the time there is must in sensitizing range, glucose oxidase identification glucose molecule with it reaction, cause the physical quantity such as mass loading, viscosity of sensitizing range to change, the surface acoustic wave parameter of device also changes thereupon, just can detect glucose content by quantitative detection frequency drift, phase place variation or time delay.
Surface acoustic wave glucose sensor has following several advantage: 1, high sensitivity and high precision: because the finger width of the interdigital transducer of SAW (Surface Acoustic Wave) device can adopt semiconductor planar processes to 300nm left and right, therefore the detection fundamental frequency of surface acoustic wave glucose sensor can be up to the even thousands of MHz of hundreds of, and this detection for the little glucose molecule of quality is very important.Adopt in addition the glucose sensor that surface acoustic wave techniques is made to export with frequency or phase signal in the time of work, do not need to become digital signal through analog-signal transitions, can directly be connected with computing machine, thereby precision is higher.2, specificity is good, antijamming capability is strong: surface acoustic wave glucose sensor adopts the fabulous glucose oxidase of specificity to identify glucose molecule, by make detecting sensor and reference sensor on a substrate simultaneously, peripheral difference channel obtains the poor sub-signal between detecting sensor and reference sensor, just can detect glucose content by quantitative test differential signal, the error that therefore external environment causes can be eliminated substantially.3, repeatability and reliability are high: the key position of surface acoustic wave glucose sensor---SAW (Surface Acoustic Wave) resonator and lag line, when making, adopt semiconductor planar technique, and repeatability is fabulous.And easy of integrationization, integrated, sound construction, good reliability.4, making and use cost are low: surface acoustic wave glucose sensor adopts semiconductor planar technique to produce in batches, and its volume is little, and the starting material of employing are few, and therefore its cost of manufacture is low; Surface acoustic wave glucose sensor is to detect glucose content by detecting frequency drift, phase place variation or time delay, does not therefore need to use expensive disposable glucose test paper, and therefore its use cost is low.
Below by accompanying drawing and example, technical scheme of the present invention is described in further detail.
Brief description of the drawings
The schematic diagram that a kind of surface acoustic wave glucose sensor that Fig. 1 provides for the embodiment of the present invention 1 is connected with peripheral difference channel.
Fig. 2 adopts respectively the glucose solution of 2mM, 4mM, 6mM, 8mM, 12mM and six kinds of variable concentrations of 16mM to detect the response of the surface acoustic wave glucose sensor proposing in embodiment 1.
Fig. 3 is for adopting respectively glucose, ascorbic acid, lactic acid and the uric acid of same concentrations (4mM) to detect the interference free performance of the surface acoustic wave glucose sensor that embodiment 1 proposes.
Fig. 4 is that the surface acoustic wave glucose sensor that adopts respectively the glucose solution of 4mM and two kinds of variable concentrations of 12mM to propose embodiment 1 carries out reperformance test.
In Fig. 1,1-Si substrate, the reflecting grating of 2-resonator, 3-inputs interdigital transducer, 4-output interdigital transducer
Embodiment
The surface acoustic wave glucose sensor that the present invention proposes can utilize many suitable materials to make; to be illustrated by specific embodiment below; certainly the present invention is not limited to following specific embodiment, and the known general replacement of one of ordinary skilled in the art is all encompassed in protection scope of the present invention undoubtedly.
Embodiment 1
As shown in Figure 1, on same Si substrate, first deposit SiO
2film, and then deposition ZnO piezoelectric film is as piezoelectric substrate, adopt photoetching process processing two-way SAW (Surface Acoustic Wave) resonator at the upper surface of described piezoelectric substrate, therein between the input and output transducer of a road resonator by the method fixing glucose oxidase of chemical crosslinking, make detecting sensor; On another road resonator without fixing glucose oxidase as reference sensor, two-way sensor is connected with peripheral difference channel, peripheral difference channel comprises amplifier, frequency mixer, wave filter, comparer, frequency counter, is finally directly connected with computing machine by interface.In the time all there is the grape solution of certain content in the sensitizing range of detecting sensor and reference sensor, the glucose oxidase identification glucose molecule of detecting sensor reaction with it, cause the mass loading of sensitizing range to change, there is drift in the frequency of corresponding resonator, and detecting sensor is because of non-specific adsorption, temperature variation, humidity changes, viscosity changes, and the frequency drift amount of the frequency drift amount that causes of other biological composition and reference sensor is identical, effectively eliminate by peripheral difference channel the frequency drift amount that extraneous factor causes, finally only be left at computer export the frequency drift causing due to glucose, just can quantitative test glucose content by analysis frequency drift value.
Embodiment 2
Fig. 2 has shown the response of the glucose solution detection surface acoustic wave glucose sensor that adopts 2mM, 4mM, 6mM, 8mM, 12mM and six kinds of variable concentrations of 16mM.The differential frequency drift value of surface acoustic wave glucose sensor is with glucose
Splash into and increase sharply, and when the response of six kinds of glucose content detecting sensors, the differential frequency drift value of surface acoustic wave glucose sensor all reaches stationary value in 100s; Along with concentration of glucose increases, the stationary value of the differential frequency drift value of surface acoustic wave glucose sensor increases, and illustrates by differential frequency drift value and really can reflect concentration of glucose.
Embodiment 3
When Fig. 3 has shown the glucose that splashes into respectively same concentrations (4mM), ascorbic acid, lactic acid and uric acid, the differential frequency drift value of surface acoustic wave glucose sensor.Just having started to add fashionable, all can there is differential frequency drift in all solution a little, and along with time duration, while adding ascorbic acid, lactic acid and uric acid, the drift of the differential frequency of surface acoustic wave glucose sensor diminishes gradually, finally and not adds fashionable almost similar; And the differential frequency drift value of surface acoustic wave glucose sensor increases gradually while adding glucose, be finally stabilized in 7.5MHz left and right.Therefore can find out that the surface acoustic wave glucose sensor proposing in embodiment 1 has good interference free performance.
Embodiment 4
Fig. 4 has shown that the glucose solution that adopts respectively 4mM and two kinds of variable concentrations of 12mM carries out reperformance test to the surface acoustic wave glucose sensor proposing in embodiment 1.In 10 hours, carry out 12 cycle alternations the glucose solution of 4mM and two kinds of variable concentrations of 12mM is splashed into the sensitizing range of surface acoustic wave sensor, the glucose solution of corresponding 4mM and two kinds of concentration of 12mM, the differential frequency drift value of surface acoustic wave glucose sensor is all highly stable, is respectively 7.5MHz and 21.8MHz left and right.Therefore can find out that the surface acoustic wave glucose sensor proposing in embodiment 1 has good repeatability and stability.
In addition, in actual use, surface acoustic wave glucose sensor need to be encapsulated, protect input and output interdigital transducer and associated components, thereby can further improve the performance such as accuracy and reliability of surface acoustic wave glucose sensor.
In sum, the present invention adopts the principle of surface acoustic wave biology sensor to make a kind of new type of SAW glucose sensor, it is little that this glucose sensor has volume, cost of manufacture is low, highly sensitive, antijamming capability is strong, the advantage such as reproducible, while being applied to blood sugar test, just can measure blood-sugar content without use blood sugar test paper, will be at food, the field such as medical industry and environmental monitoring, also in clinical examination, blood sugar being carried out to monitoring field with sensitivity has broad application prospects, particularly can play a significant role to diabetes patient's blood sugar monitoring.
Claims (10)
1. a surface acoustic wave glucose sensor, is characterized in that, comprises monocrepid two-way surface acoustic wave sensor and peripheral difference channel; Wherein, described monocrepid two-way surface acoustic wave sensor is to make detecting sensor and reference sensor on a substrate simultaneously, between the input and output transducer of detecting sensor, apply glucose oxidase glucose to high degree of specificity, form sensitizing range, between the input and output transducer of reference sensor, do not apply glucose oxidase, its Main Function is to reduce the error that external environment causes; Described surface acoustic wave glucose sensor adopts piezoelectric as substrate, makes two pairs of input and output transducers on substrate, forms and detects and reference sensor; Described surface acoustic wave sensor comprises delay line type and mode of resonance surface acoustic wave sensor; Described peripheral difference channel, for obtaining the poor sub-signal between detecting sensor and reference sensor, just can detect glucose content by quantitative test differential signal.
2. surface acoustic wave glucose sensor according to claim 1, is characterized in that, described surface acoustic wave glucose sensor adopts piezoelectric as substrate, and described piezoelectric is piezoelectricity block and piezoelectric membrane.
3. surface acoustic wave glucose sensor according to claim 2, is characterized in that, described piezoelectricity block is the piezoelectricity block materials such as lithium niobate, lithium tantalate, PZT, quartz.
4. surface acoustic wave glucose sensor according to claim 2, is characterized in that, described piezoelectric membrane is the piezoelectric membranes such as ZnO, AIN, PZT, PVDF, lithium niobate, lithium tantalate.
5. surface acoustic wave glucose sensor according to claim 1, is characterized in that, described surface acoustic wave sensor comprises delay line type and mode of resonance surface acoustic wave sensor.
6. surface acoustic wave glucose sensor according to claim 1, is characterized in that, on a substrate, makes detecting sensor and reference sensor simultaneously, in detecting sensor, applies glucose is had to specific glucose oxidase.
7. surface acoustic wave glucose sensor according to claim 1, is characterized in that, described differential signal comprises frequency, phase place, time delay etc.
8. a method for making for surface acoustic wave glucose sensor, is characterized in that, comprising: make piezoelectric; On described piezoelectric, make surface acoustic wave detecting sensor and reference sensor; Between the input and output transducer of described detecting sensor, apply glucose oxidase, form sensitizing range, described surface acoustic wave glucose sensor is connected to peripheral difference channel.
9. the method for making of surface acoustic wave glucose sensor according to claim 8, it is characterized in that, described piezoelectric is piezoelectricity block (the piezoelectricity block materials such as lithium niobate, lithium tantalate, PZT, quartz) and piezoelectric membrane (piezoelectric membrane such as ZnO, AIN, PZT, PVDF, lithium niobate, lithium tantalate).
10. the method for making of surface acoustic wave glucose sensor according to claim 8, it is characterized in that, between the input and output transducer of described detecting sensor, apply glucose is had to specific glucose oxidase, by the method fixing glucose oxidase of physisorption or chemical crosslinking, form sensitizing range.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN109917000A (en) * | 2018-12-04 | 2019-06-21 | 深圳大学 | PbS Colloidal Quantum Dots thin-film sound surface wave gas sensor |
| CN110432911A (en) * | 2018-05-02 | 2019-11-12 | 中国科学院苏州纳米技术与纳米仿生研究所 | Surface acoustic wave glucose sensor and preparation method thereof |
| CN112305042A (en) * | 2020-10-22 | 2021-02-02 | 成都天巡星网科技有限责任公司 | Microminiaturized unmarked glucose biosensor based on microwave technology |
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Cited By (3)
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| CN110432911A (en) * | 2018-05-02 | 2019-11-12 | 中国科学院苏州纳米技术与纳米仿生研究所 | Surface acoustic wave glucose sensor and preparation method thereof |
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| CN112305042A (en) * | 2020-10-22 | 2021-02-02 | 成都天巡星网科技有限责任公司 | Microminiaturized unmarked glucose biosensor based on microwave technology |
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Application publication date: 20140820 |