CN1540330A - Nano sensor in use for early diagnosing diabetes and preparation method - Google Patents

Abstract

The sensor is composed of combined Ag+ZSM-5 sensing film with mass sensor QCM in piezoelectric type resonance. The sensor possesses distinct response to acetone gas as characterization index for diabetes. The sensor can detect concentration of acetone molecule in exhalant air from human body. The value of concentration can be as aid for diagnosing diabetes and reference of self-diagnosis system for early state of illness. The invention features of simple structure, good repeatability.

Description

A kind of nano-sensor that is used for the diabetes early diagnosis and preparation method thereof

Technical field

The invention belongs to sensor technical field, be specifically related to a kind of nano-sensor that is used for the diabetes early diagnosis.

Background technology

Can detect hundreds of kind escaping gas in the human body breath, wherein part is relevant with disease ^[1]For example, acetone gas is indicating uremia (as the diabetic), and dimethylamine gas is then relevant with liver diseases, or the like.Therefore, diagnose the health state to cause medical circle concern [2] very by the human body breath.It not only can not need the mode of any intrusion human body to implement state of an illness diagnosis fast under nonpoisonous state, and can provide an important new visual angle for further grasping the basic biochemical function of human body.By the detection to patient expired gas molecule, the diagnosis that realizes multiple disease is highly effective.

In the world, ground zero is gone back in the research of the sensor of human body breath, and the type of report has following several usually: (metal-oxide semiconductor (MOS) is as SnO for MOS ₂, CdO ₂, Nb ₂O ₅Deng) ^[2], EC (galvanochemistry) ^[3], BAW (acoustic bulk wave)/SAW (surface acoustic wave) ^[1]And CP (conducting polymer) ^[4]Deng.Surveying the preliminary examination of the content of special gas in the human body expiration as health status, is one of convenient and swift means of family's self check or general survey.But, yet there are no by surveying sensor and the method that special gas comes diagnosing diabetes in the human body breath.

List of references:

[1]Y-J?Lin，H-R?Guo，et?al.“Application?of?the?electronic?nose?for?uremia?diagnosis”，Sensorsand?Actuators，B?76(2001)177-180

[2]S.V.Ryabtsev，A.V.Shaposhmick，et?al，“Application?of?semiconductor?gas?sensors?formedical?diagnostics”，Sensors?and?Actuators，B?59(1999)26-29.

[3]J.W.Gardner，H?W.Shin，et?al，“An?electronic?nose?system?to?diagnose?illness”，Sensors?andActuators，B?70(2000)19-24.

[4]K.C.Persaud，P.J.Travers，“Arrays?of?broad?specificity?films?for?sensing?volatile?chemicals”，in：E.Kress-Rpger(Ed)，Haadb.Biosens.Electron.Noses，CRC?Press，Ohio，1997，pp.563-592.

[5]J.W.Gardner.Microsensors-Principles?and?Applications.John?Wiley?&?Sons，New?York：1994.

[6]Bozhi?Tian，Xiaoying?Liu，Haifeng?Yang，Songhai?Xie，Chengzhong?Yu，Bo?Tu?and?DongyuanZhao.General?Synthesis?of?Ordered?Crystallized?Metal?Oxide?Nanoarrays?Replicated?byMicrowave?Digested?Mesoporous?Silica.Adv.Mater.，2003，15，1370-1374

[7]Haifeng?Yang，Qihui?shi，Bozhi?Tian，Qingyi?Lu，Feng?Gao，Songhai?Xie，Jie?Fan，Chengzhong?Yu，Bo?Tu，and?Dongyuan?Zhao.One-Step?Nanocasting?Synthesis?of?HighlyOrdered?Single?Crystalline?Indium?Oxide?Nanowire?Arrays?from?Mesostructured?Frameworks.J.Am.Chem.Soc.，2003，125，4724-4725.

Summary of the invention

The objective of the invention is to propose a kind of by surveying the special composition in the human body breath, sensor of early diagnosis diabetes and preparation method thereof.

Medical research shows that the content of the acetone gas in the human body breath is the important characteristic index of diabetes, therefore, detects the concentration of acetone in the breath, can be the early diagnosis diabetes foundation is provided.According to the size of acetone molecules, the molecular sieve of Nano zeolite material that the present invention has found a kind of silver ion to modify, it has unique response to acetone, promptly acetone is had very high selectivity.In addition, piezo-electric resonance type mass sensor QCM (Quartz Crystal Microbalance) has very high sensitivity.Therefore, as sensitive membrane, QCM combines with the piezo-electric resonance type mass sensor with the nano molecular sieve material in the present invention, is configured for the nano-sensor of early diagnosis diabetes.

The preparation method of the nano-sensor that the present invention proposes is as follows:

A. to the prerinse of QCM quartz wafer, so that micronic dust, metallic ion and organism on the removal wafer;

B. Ag ⁺ZSM-5 nano molecular sieve material grind into powder (general particle diameter＜0.1 micron) is so that make molecular sieve and even, the firm bonding of QCM;

C. Ag ⁺The ZSM-5 powder is scattered in absolute ethyl alcohol, and is placed on and carries out sonicated in the ultrasound wave mixed instrument, until the suspending liquid that becomes homogeneous.General Ag ⁺The weight proportion of ZSM-5 and absolute ethyl alcohol is 1: 20-1: 100, specifically can determine according to the thickness that applies rete;

D. stop ultrasonicly, the QCM quartz wafer is immersed in the suspending liquid, take out immediately, remove the drop of thereupon taking out of;

E. scribbling Ag ⁺The QCM quartz wafer of ZSM-5 molecular sieve is warming up to 200-300 ℃, keeps 20-30 minute in this temperature, to remove ethanol and to make QCM and molecular sieve bonding well;

F. repeating step d and the e sensitive membrane thickness to obtain needing as required is to satisfy the requirement of sensor resonant frequency.

The principle of work of sensor is described below:

Resonant mode mass sensor QCM under the driving of voltage with fundamental vibration.Flow into gas sensor when containing certain density acetone gas, acetone molecules then is applied to the nano molecular sieve absorption on QCM surface rapidly, and the change of this small quality causes the QCM change of resonance frequency immediately, according to the Sauerbrey equation ^[5], can know:

Δf＝-2.26×10 ^-6f ²Δm/A

Wherein, Δ m is the change (unit is g) of mass loading, and f is the frequency of operation (unit is Hz) of quartz crystal, and Δ f is the caused frequency shift of load quality change amount Δ m, and A is that (unit is cm for the area of quartz crystal ²), negative sign represents that the increase of QCM surface quality will cause its frequency to descend.

The change of said frequencies is sent into computing machine through data acquisition after being detected by frequency meter, is presented on the screen and/or stores.Repeatedly to the measurement result of the acetone gas of different concentration known through statistical study and simulation as calculated, obtain the calibration curve of this sensor, see Fig. 2.Can check content of acetone in the unknown tested gas in real time by this curve.

Among the present invention, piezo-electric resonance type mass sensitivity device obtains the variation of mass of system by the change of detection system resonance frequency; By different pore sizes, shape and through the nano molecular sieve material of chemical modification as the gas sensitization film, be produced on the sensor spare with certain technology.After gas enters detecting sensor, wherein specific acetone gas molecule will be optionally by the absorption of air-sensitive nano molecular sieve membrane and attached on the piezo-electric resonance type mass sensitivity device, therefore cause the variation (this variable quantity size is relevant with the concentration of this specific gas) of mass of system, and then caused the variation of system resonance frequency.So the variation of system resonance frequency promptly indicates the concentration that contains the specific gas relevant with various diseases in the human body breath, this concentration value promptly can be used as the supplementary means of diabetes state of an illness diagnosis and the reference of the computer-aided diagnosis system of the state of an illness in early days.

Sensor construction provided by the invention is simple, and is cheap, can distinguish normal person and diabetes patient's breath fully, and good reproducibility can repeatedly use, and is applicable to that hospital's diabetes large tracts of land generaI investigation and family test oneself in early days.

Description of drawings

Fig. 1 medical diagnosis on disease sensing system synoptic diagram.

Fig. 2 sensor acetone concentration---frequency response calibration curve.

The sensitivity qualification result of Fig. 3 sensor.Wherein, Fig. 3 (a) is the response curve (Ag of 4.5ppm-29ppm for acetone concentration in nitrogen ⁺The thickness of ZSM-5 is 1.5 microns), Fig. 3 (b) is the response curve (Ag of 1.2ppm-7.8ppm for acetone concentration in nitrogen ⁺The thickness of ZSM-5 is 2 microns).

Fig. 4 sensor selectivity test curve.

Fig. 5 sensor replica test result.

The test that Fig. 6 sensor is exhaled to the diabetes patient.Wherein, Fig. 6 (a) is a response curve, and Fig. 6 (b) is the visual in image figure of curve after data processing among Fig. 6 (a).

Embodiment

The preparation of nanometer gas sensor.

QCM continues with absolute ethyl alcohol ultrasonic cleaning 30 minutes after at first cleaning 30 minutes with 1% oxalic acid,, dries 30 minutes for 200 ℃, to guarantee QCM cleaning surfaces drying after 5 minutes through deionized water rinsing.Ag ⁺The ZSM-5 nano molecular sieve, after agate Yan Portland grinds 30 minutes, add proper C MOS absolute ethyl alcohol sonicated in the ultrasound wave mixed instrument and become suspension liquid after 30 minutes, to clean dry QCM then in advance is dipped in this suspending liquid, take out and place clean double dish immediately, in 200 ℃ of baking boxs, behind hour desorb ethanol of baking, promptly finish the coating of one deck nano molecular sieve membrane.Repeat above-mentioned steps, reach 7.97MHz until the resonant frequency (being 8MHz before being coated with molecular sieve) of this QCM.QCM behind the coated with nano molecular sieve puts into drying box and deposits in order to using.

The structural representation of entire measuring device is seen Fig. 1.It mainly is made up of three parts: gas preprocessing part, Sensor section and test section.Owing to contain a large amount of steam in the human body breath, can cause very big interference to detection, therefore the important process step for the human body breath is to adopt the way of physics condensation to remove moisture content.Generally can adopt the refrigeration structure of semiconductor chilling plate and three grades of adiabatic gas expansions, making water vapour in the sample gas in the dehumidifying chamber of flowing through be cooled into little globule and reaching separating of moisture and gas, do not influence the concentration of original gaseous sample to be measured again, cancellation steam is treated the influence of surveying gas substantially.Sensor section is the core of device, promptly adopts QCM of the present invention through applying gas sensitive Ag ⁺The sensor that ZSM-5 constitutes.Gas causes the QCM frequency shift and then is converted into electric signal by this part to be exported from the test section.The sensor main performance index

Sensor reaches 1.2ppm to the minimum detectable concentration of acetone gas, and sensitivity is-0.00088%Hz/ppm (as Fig. 3) that Fig. 4 shows that then this sensor has good selectivity to acetone gas.

Figure 5 shows that QCM sample tube sensor to variable concentrations acetone gas repeated experiment, the gas of pure nitrogen gas, 5ppm and three kinds of concentration of 10ppm has all been carried out twice measurement to prove its repeatability.As can be seen from the figure the response time of this sensor is approximately 90 seconds, good reproducibility.

The sample pipe is to the detection of diabetes patient's breath

We have gathered 11 diabetes patients' expiration, and detect, and the results are shown in Figure 6, and as we can see from the figure, this sample pipe can be distinguished diabetes patient and normal person fully.Table 1 has provided patient's blood glucose value and the resonance frequency change value of correspondence when detecting, and the content of acetone value in the patient exhales that obtains according to sample pipe calibration curve.Its content of acetone meets the scope of the said 0.1～10ppm of document [1], and the practicality of this sensor has been described.

Claims (2)

1, a kind of nano-sensor that is used for the diabetes early diagnosis is characterized in that with nano molecular sieve materials A g ⁺ZSM-5 is as sensitive membrane, combines with piezo-electric resonance type mass sensor QCM and constitutes.

2, a kind of preparation method who is used for the nano-sensor of diabetes early diagnosis is characterized in that concrete steps are as follows:

A. to the prerinse of QCM quartz wafer;

B. Ag ⁺ZSM-5 nano molecular sieve material grind into powder;

C. with Ag ⁺ZSM-5 is scattered in the absolute ethyl alcohol, and is placed on and carries out sonicated in the ultrasound wave mixed instrument, until the suspending liquid that becomes homogeneous;

D. stop ultrasonicly, the QCM quartz wafer is immersed in the suspending liquid, take out immediately, remove the drop of thereupon taking out of;

E. scribbling Ag ⁺The QCM quartz wafer of ZSM-5 molecular sieve is warming up to 200-300 ℃, and keeps 20-30 minute in this temperature, to remove ethanol and to make QCM and molecular sieve bonding well;

F. repeating step d and e are until the sensitive membrane thickness that needing to obtain.

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