CN101490539A - Self-exciting, self-sensing piezoelectric cantilever sensor for detection of airborne analytes directly in air - Google Patents

Self-exciting, self-sensing piezoelectric cantilever sensor for detection of airborne analytes directly in air Download PDF

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Publication number
CN101490539A
CN101490539A CNA2007800260308A CN200780026030A CN101490539A CN 101490539 A CN101490539 A CN 101490539A CN A2007800260308 A CNA2007800260308 A CN A2007800260308A CN 200780026030 A CN200780026030 A CN 200780026030A CN 101490539 A CN101490539 A CN 101490539A
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sensor
piezoelectric layer
piezoelectric
cantilever
attached
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拉贾坎努·穆萨拉尚
大卫·L·戴尔斯德涅尔
戈塞特·坎贝尔
大卫·马拉尔杜
彼得·A·纳吉
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Drexel University
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2291/00—Indexing codes associated with group G01N29/00
    • G01N2291/04—Wave modes and trajectories
    • G01N2291/042—Wave modes
    • G01N2291/0427—Flexural waves, plate waves, e.g. Lamb waves, tuning fork, cantilever

Abstract

The invention relates to a method for detection of airborne biological agent using a piezoelectric cantilever sensor that includes a piezoelectric layer and a non-piezoelectric layer. A recognition entity is placed on one or both of the two layers. The antibody that recognizes and binds to the airborne species may be chemically immobilized on the cantilever sensor surface. In one embodiment, the cantilever sensor is attached to a base at only one end. In another embodiment, the sensor includes first and second bases and at least one of the piezoelectric layer and the non-piezoelectric layer is affixed to each of the first and second bases to form a piezoelectric cantilever beam sensor. In this embodiment, resonance is measured via stress on the piezoelectric layer and it has been demonstrated that such sensors are robust and exhibit excellent sensing characteristics in gaseous media with sufficient sensitivity to detect airborne species at relatively low concentrations.

Description

Directly in air, detect the self-excitation self-induction type piezoelectric cantilever sensor of airborne analyte
Quoting mutually of related application
The application requires to submit on January 23rd, 2007, name is called the U. S. application No.11/625 of " Self-Exciting, Self-Sensing Piezoelectric Cantilever Sensor ", 919 right of priority, and it is all incorporated into here by reference.U. S. application 11/625,919 require on January 23rd, 2006 submit to name is called " PIEZOELECTRIC CANTILEVER SENSORS; " U.S. Provisional Patent Application No.60/761,172 and on July 11st, 2006 submit to name is called " PIEZOELECTRIC CANTILEVER SENSORS; " U.S. Provisional Patent Application No.60/807,020 right of priority, these two temporary patent applications are all incorporated into here by reference.The application also requires the U.S. Provisional Patent Application No.60/746 that is called " Detection of AirbornePathogens Directly in Air, " in submission on May 10th, 2006,951 right of priority, and it is all incorporated into here by reference.
Technical field
Present technique field relate generally to sensor, and more particularly relates to piezoelectric cantilever sensor and relates to and utilize piezoelectric cantilever sensor to detect and the Measurement and analysis thing.
Background technology
Cantilever sensor can be divided into two types substantially according to the size of sensor: micro-cantilever and big cantilever.The micro-cantilever sensor can and dynamically use in (resonance) pattern in static (bending) pattern.In static schema, the deformation of the arm of measurement cantilever is to determine whether to exist analyte (analyzed material).In dynamic mode, measure resonant frequency to determine whether to exist analyte.Big cantilever sensor does not use in static schema because the bending of the arm of cantilever usually is limited usually.Big cantilever sensor can use in the liquid infiltration condition or in gas or vacuum.Compare the sensitivity that can reach higher when usually, cantilever sensor uses when in liquid, using in gas/vacuum.Fluid damping is tending towards influencing unfriendly sensitivity.Yet the Measurement and analysis thing has many practical applications in liquid medium.
One type known micro-cantilever sensor is silica-based micro-cantilever sensor.The silica-based micro-cantilever sensor of typical silicon-based comprises the micro-cantilever as resonator.Micro-cantilever drives to produce vibration at resonator by the external actuator that is arranged in the micro-cantilever bottom.Usually, detect vibration by the external optical detection device.A shortcoming of typical silica-based micro-cantilever is to detect to need complicated external optical elements.In addition, optical detection means that the application with the micro-cantilever sensor is restricted to the sample that cleans on the optics unfriendly.Another shortcoming is because external actuator and the weight and the complexity that increase to sensor.Another shortcoming is the bottom that external actuator can only be positioned at micro-cantilever, and this has limited its efficient when driving the vibration of cantilever.Another shortcoming of silica-based micro-cantilever sensor is that they mechanically are frangible.Therefore, silica-based micro-cantilever sensor can not use in the environment of high flow rate of liquid.In addition, typical silica-based micro-cantilever sensor in liquid medium owing to viscous damping is lost detection sensitivity.
The known cantilever sensor of another kind of type is the silica based piezoelectric cantilever sensor.Quartz has weak piezoelectricity, and is therefore very similar with silica-based cantilever sensor, the silica based piezoelectric cantilever sensor in liquid medium owing to viscous damping is lost detection sensitivity.In addition, the detection sensitivity of silica based sensor is subjected to the restriction of sensor plane geometric configuration.
The piezoelectric cantilever of known conventional is used in that the piezoelectric layer that is attached to non-piezoelectric layer on the partly or completely surface of piezoelectric layer makes.In some traditional piezoelectric cantilevers, piezoelectric layer at one end is fixed and makes that non-piezoelectric layer bending is to adapt to the strain that causes in the piezoelectric when piezoelectric is subjected to encouraging.When the natural frequency of the frequency of excitation and following physical construction is identical, resonate.Known such piezoelectric cantilever sensor moves with the frequency that is lower than about 100kHz under mm size.At present, only by make cantilever sensor lack very much (length is less than 1.0mm), very narrow (width is less than 0.1mm) and extremely thin (thickness is less than 100 microns) obtains higher frequency.Yet, reduce the size of cantilever sensor, particularly width, thereby, make cantilever sensor in liquid medium owing to viscous damping has reduced workability.Square oppositely increase of damping and cantilever width.
Up-to-date biosensor technique depends on fluorescence, laser, the method based on optical fiber, QCM (Quartz Crystal Microbalance) technology, electrochemical enzymatic immunoassays and/or is attached to metallic particles.Great majority in these technology are not again quantitative directly neither.Many also very slow in these technology.In addition, most of aforementioned techniques are not suitable for measuring the variation of quality, and the variation of quality can provide the mode easily of measuring various different parameters.
Mass sensor based on resonant frequency needs three assemblies: actuator (driver), resonator and detecting device.An example of mass sensor is silica-based micro-cantilever, and it can easily be integrated with existing silicon based approach.In silica-based micro-cantilever mass sensor, micro-cantilever drives to produce vibration at resonator as resonator and by outside lead zirconate titanate (PZT) actuator that is arranged in the micro-cantilever bottom, and this vibration can detect by the external optical detection device.For biological detection, acceptor is fixed on the cantilever surface.Antigen is bound to and is fixed on the lip-deep acceptor of cantilever, and this is in conjunction with the quality that increases cantilever and cause the decline of resonant frequency.The detection of target molecule realizes by the monitoring mechanical resonance frequency.Although silica-based micro-cantilever receives an acclaim, they still depend on the external optical elements of the complexity that is used to detect.In addition, the PZT vibratory driver has increased the weight and the complexity of sensor.In addition, external actuator can only be positioned at the bottom of micro-cantilever, and this has limited it widely in the efficient that drives on the cantilever vibration.The sample that optical detection apparatus also cleans application limitations to the optics.
Except quality testing, silica-based micro-cantilever is also as the micromolecule sensor, and this is to be adsorbed onto on the acceptor related with cantilever and the stress that produces on cantilever is realized this micromolecule sensor by detecting by material.Antibody or DNA acceptor are coated on the surface of micro-cantilever with the constraint target biological molecules.The stress that target molecule is bound to the lip-deep acceptor of micro-cantilever or is produced when target molecule discharged from it causes the deviation of micro-cantilever, and this deviation can be by external optical elements or the dc voltage detection by absorption-stress-induction on the lip-deep piezoelectricity-resistive coating of cantilever.
Compare with silicon based sensor, the piezoelectric cantilever sensor of mm size is so not huge and complicated.Because therefore short response time and high piezoelectric modulus, piezoelectric device are excellent transducing candidate devices.Because they are piezoelectricity, therefore driving and the sensing that in resonator, can carry out mechanical resonance easily with electric mode ground.At present, piezoelectric biological sensor based on commercially available available QCM (Quartz Crystal Microbalance) (QCM), utilize thickness mode resonance to carry out the disc type device of sensing.Though quartz is weak piezoelectric, yet partly because big single crystal quartz can be used for making film, so quartz is widely used as part layer thickness monitor device.Has minimum detectable mass density (DMD) 10 -9G/cm 2The typical quality testing sensitivity of 5MHz QCM be about 10 -8G/Hz is than low about four orders of magnitude of the sensitivity of the piezoelectric cantilever of mm size.
Existing micro-cantilever is about 100 microns long, and tens microns wide, and a few micron thickness.This micro-cantilever uses in bending or resonant mode to be used for detection.The shortcoming of these micro-cantilevers is that their resonance characteristics descends very sharp owing to viscous damping.In addition, their uses in liquid medium realize under the low-down flow rate conditions of mul/min.
D.W.Carr and H.G.Craighead, " Fabrication ofnanoelectromechanical systems in single crystal silicon using silicon oninsulator substrates and electron beam lithography ", J.vac.Sci.Technology.B., 15 (6), 1997.2760-2763 page or leaf, disclose the beam sensor of net form structure of about hundreds of nanometer and the manufacturing of many beam sensors, and realized the high resonant frequency of 40MHz.The name of submitting on January 23rd, 2007 is called the common unsettled U. S. application No.11/659 of " Self-Exciting; Self-SensingPiezoelectric Cantilever Sensor ", the 919th, by the common invention of the inventor, and it has discussed the structure and the basic operation of the cantilever sensor of the piezoelectric excitation of mm size in the fluid sample sublimity.
Therefore, need to improve the sensor that the sensing ability of existing sensor and need providing has the ability that airborne material is detected of improvement.
Summary of the invention
The self-excitation and the piezoelectric cantilever sensing device of self-induction type comprise piezoelectric layer and be attached to the non-piezoelectric layer of this piezoelectric layer, thereby the remote extension of this non-piezoelectric layer is above the remote extension of the far-end of this piezoelectric layer or this piezoelectric layer far-end above this non-piezoelectric layer.That is, this piezoelectric layer is connected to this non-piezoelectric layer, thereby this piezoelectric layer and this non-piezoelectric layer are not coextensive.In the various structures of this piezoelectric cantilever sensing device, piezoelectric layer, non-piezoelectric layer or both anchor at least one substrate.Electrode is operatively related with piezoelectric layer.This self-excitation self-induction type piezoelectric cantilever sensor is used for the sensing mass change.In order to determine the quality of analyte on the sensing device, measure the resonant frequency of the mechanical part of this cantilever sensor.Resonant frequency and the baseline resonant frequency measured are compared to determine the poor of frequency.The difference of this frequency is represented the quality of analyte on the sensing device.
According to embodiments of the invention, realized detecting airborne pathogen in air and do not needed sample collection in the liquid or solid matrix.According to an aspect, realize target analytes by sensing device being exposed to airborne analyte, such as the air borne detection method of biological or chemical material.When analyte is present in the gas, is positioned at identification body on the sensing device and is bound to analyte and can be detected.Concrete example identification body comprises the immersion coating that is used for detection of chemicals and is used for the sessile antibody of detection of biological product.
In one aspect of the invention, sensing device comprises sensor, and this sensor comprises piezoelectric layer, non-piezoelectric layer and is arranged in identification body on the two-layer arbitrary layer.In first embodiment, sensor is only at one end fixing slider assembly.Here, piezoelectric layer is connected to substrate and non-piezoelectric layer are attached to piezoelectric layer with overlap mode end.Electrode is attached to piezoelectric layer and is driven with the resonance of excitation piezoelectric layer by electricity.In the time of in being exposed to airflow, identified region on the non-piezoelectric layer attracts analyte and causes the mass change of the cantilever that combination and identified region by piezoelectric layer and non-piezoelectric layer form.The variation that resonant frequency when determining attached analyte is compared with baseline resonant frequency and this frequency displacement represent to discern the amount of analyte fixing on the body.
The formation that can change sensor is to adapt to different frequency detecting points.Second type sensor relates to the beam type sensor that the wherein non-piezoelectric layer of use is attached to the underlying structure on the two ends.Piezoelectric layer is placed on the non-piezoelectric layer and is energized as mentioned above with resonance.Identification body on non-piezoelectric layer or the piezoelectric layer causes mass change and causes the frequency displacement of the resonant frequency of beam sensor when being exposed to the analyte of atomizing.Therefore, can check and analysis thing and definite its quality.The sensor of the third type is the modification of beam sensor, and wherein piezoelectric layer is the top that beam and non-piezoelectric layer are attached to this beam.
The device that detects airborne analyte comprises exposing manages, and this exposure pipe contains the cantilever sensor that is attached to atomizer, and described atomizer makes analyte exist in crossing the airflow of sensor the analyte atomizing.The resonant frequency of analyser survey sensor has also determined whether and has how many analytes to be present in the airflow.
These and various other advantages and the feature that characterize novelty of the present invention are pointed out in claim appended and that form this instructions part particularly.Yet in order to understand the present invention better, its advantage and use the purpose that obtains by it should be with reference to accompanying drawing that constitutes the another part of this instructions and appended descriptive content, shown in it and described the preferred embodiments of the present invention.
It partly is in order to introduce the selection of the notion that will embodiment below partly further describes in simplified form that this summary of the invention is provided.This summary of the invention partly is not intended to key feature or the principal character of determining claim, also is not intended to the scope that is used to limit the claim main contents.
Description of drawings
Understand specifying of aforementioned summary of the invention and back when read in conjunction with the accompanying drawings better.For self-excitation self-induction type piezoelectric cantilever sensor is described, shown its representative configuration in the accompanying drawing; Yet self-excitation self-induction type piezoelectric cantilever sensor is not limited to disclosed concrete grammar and instrument.In the accompanying drawing:
Fig. 1 is the key diagram of the representative configuration of self-excitation self-induction type piezoelectric cantilever sensor;
Fig. 2 is the sectional view of describing with the example self-excitation self-induction type piezoelectric cantilever sensor of the electrode put area of the operatively related electrode of piezoelectric layer;
Fig. 3 is the sectional view that the example self-excitation self-induction type piezoelectric cantilever sensor of the example electrode placement in the base part that is depicted in self-excitation self-induction type piezoelectric cantilever sensor is shown;
Fig. 4 is the sectional view that the example self-excitation self-induction type piezoelectric cantilever sensor of describing the not example electrode placement in the base part of self-excitation self-induction type piezoelectric cantilever sensor is shown;
Fig. 5 is the key diagram of the example constructions of self-excitation self-induction type piezoelectric cantilever sensor, and wherein the far-end of this piezoelectric layer flushes with the far-end of non-piezoelectric layer;
Fig. 6 is the key diagram of the example constructions of self-excitation self-induction type piezoelectric cantilever sensor, and wherein the remote extension of the piezoelectric layer proximal extension that surpasses the far-end of non-piezoelectric layer and piezoelectric layer surpasses the near-end of non-piezoelectric layer;
Fig. 7 is the key diagram of example constructions with self-excitation self-induction type piezoelectric cantilever sensor of two base part;
Fig. 8 is the key diagram of another example constructions of self-excitation self-induction type piezoelectric cantilever sensor, and wherein piezoelectric layer is not attached in two base part one;
Fig. 9 is the key diagram of example constructions of self-excitation self-induction type piezoelectric cantilever sensor with piezoelectric layer of anchored ends;
Figure 10 is the key diagram of the example constructions of self-excitation self-induction type piezoelectric cantilever sensor, and wherein piezoelectric layer comprises two parts, and one of them part is anchored;
Figure 11 is another key diagram of the example constructions of self-excitation self-induction type piezoelectric cantilever sensor, and wherein piezoelectric layer comprises two parts, and one of them part is anchored;
Figure 12 is the key diagram of the example constructions of self-excitation self-induction type piezoelectric cantilever sensor, and wherein piezoelectric layer comprises two parts that all are not anchored;
Figure 13 has the non-piezoelectric of grappling and the key diagram of the example constructions of the self-excitation self-induction type piezoelectric cantilever sensor of the piezoelectric that is not anchored;
Figure 14 is the key diagram of the example constructions of self-excitation self-induction type piezoelectric cantilever sensor, the not attached arbitrary base part of wherein non-piezoelectric layer;
Figure 15 is the key diagram of another example constructions of self-excitation self-induction type piezoelectric cantilever sensor, and wherein piezoelectric has different width with non-piezoelectric;
Figure 16 is the key diagram of example constructions that comprises the self-excitation self-induction type piezoelectric cantilever sensor of piezoelectric layer and non-piezoelectric layer, wherein the width of piezoelectric layer is less than the width of non-piezoelectric layer 16, and the remote extension of the piezoelectric layer proximal extension that surpasses the far-end of non-piezoelectric layer and piezoelectric layer surpasses the near-end of non-piezoelectric layer;
Figure 17 is the process flow diagram that utilizes the instantiation procedure of self-excitation self-induction type piezoelectric cantilever sensor check and analysis thing;
Figure 18 is the curve map that is configured in the exemplary resonance spectrum of operating in the air of the self-excitation self-induction type piezoelectric cantilever sensor described among Fig. 1;
Figure 19 A has shown the skeleton view of the piezoelectric cantilever sensor that uses in the methods of the invention;
Figure 19 B has shown the embodiment of the cantilever beam sensor of the piezoelectric excitation of the grappling of use in the methods of the invention;
Figure 19 C has shown the embodiment of the cantilever beam sensor of the piezoelectric excitation of the unmanaged flexibility of use in the methods of the invention;
Figure 19 D has shown the embodiment of the cantilever beam sensor of the bimorph formula piezoelectric excitation of the grappling of use in the methods of the invention;
Figure 19 E has shown the embodiment of the cantilever beam sensor of the piezoelectric excitation that dangles that uses in the methods of the invention;
Figure 19 F has shown the embodiment of the cantilever beam sensor of lead zirconate titanate (PZT) piezoelectric excitation of the grappling of use in the methods of the invention;
Figure 19 G has shown the sketch according to the embodiment of unmanaged flexibility head PEMC of the present invention (ftPEMC) sensor;
Figure 20 is the aerial resonance spectrum of first embodiment (referring to the oPEMC#1 of Figure 47 table 1) of the piezoelectric cantilever sensor that dangles shown in Fig. 1;
Figure 21 is the aerial resonance spectrum of second embodiment (referring to the oPEMC#2 of Figure 47 table 1) of the piezoelectric cantilever sensor that dangles shown in Fig. 1;
Figure 22 is the aerial resonance spectrum of the 3rd embodiment (referring to the oPEMC#3 of Figure 47 table 1) of the piezoelectric cantilever sensor that dangles shown in Fig. 1;
Figure 23 is the resonance spectrum of the 4th embodiment (referring to the oPEMC#4 of Figure 47 table 1) of the cantilever sensor that dangles shown in Fig. 1;
Figure 24 is the resonance spectrum of the 5th embodiment (referring to the oPEMC#5 of Figure 47 table 1) of the cantilever sensor that dangles shown in Fig. 1;
Figure 25 has shown the grappling that encourages under 100mV PEMCB sensor (aPEMCB, Figure 19 B) in air phase angle to the resonance spectrum curve map of excitation frequency;
Figure 26 uses the curve map of phase angle to excitation frequency, has shown PEMCB (fPEMCB#1, Figure 19 C) sensor resonance characteristics under the 100mV driving voltage in air of unmanaged flexibility;
Figure 27 uses the curve map of phase angle to excitation frequency, has shown bimorph formula PEMCB (abPEMCB#1, Figure 19 D) sensor resonance spectrum under the 100mV driving voltage in air of grappling;
Figure 28 has shown the resonance spectrum that PEMCB (oPEMCB#1, Figure 19 E) sensor that dangles encourages under the 100mV voltage in air;
Figure 29 A-B has shown the device that is used to implement airborne bacillus anthracis detection;
Figure 30 A has shown the result of the test experience that is used for the detection of air bacillus anthracis;
Figure 30 B is presented at the result who is used under the situation that contrasts inorganic particle in the test experience of air bacillus anthracis detection;
Figure 31 has shown that the detection to the experiment of Figure 30 A confirms (confirmation);
Figure 33 has shown the scanning electron micrograph according to the sensor of the inventive method test, and it is presented at the anthrax spores of fixing on the surface of sensor;
Figure 33 has described humidity injector mode of the present invention;
Figure 34 is the process flow diagram of the inventive method;
Figure 35 is the sensor relief configuration;
Figure 36 is the structure of the clamping of sensor;
Figure 37 is the configuration of the alternative clamping of sensor;
Figure 38 is the replacement scheme of the sensor geometry of Figure 19 A;
Figure 39 is the another kind of alternative constructions of Figure 19 A sensor;
Figure 40 is the beam type structure of Figure 19 F;
Figure 41 is the alternative constructions of Figure 19 E;
Figure 42 is the alternative constructions of Figure 19 G;
Figure 43 is the alternative constructions of Figure 42;
Figure 44 is the alternative constructions of Figure 36;
Figure 45 is the sensor arrangement of multilayer, and wherein said layer is anchored in the substrate at least in part;
Figure 46 is the structure with substrate of modification;
Figure 47 comprises table 1;
Figure 48 comprises table 2;
Figure 49 comprises table 3; And
Figure 50 comprises table 4.
Embodiment
The self-induction type piezoelectric cantilever sensor of encouraging oneself as described herein provides the ability that detects and measure indivisible analyte.This self-excitation self-induction type piezoelectric cantilever sensor can be used in and detects and measure the analyte that contains in the analyte that is immersed in the liquid and gas or the vacuum.In various example constructions, this self-excitation self-induction type piezoelectric cantilever sensor comprises at least one piezoelectric layer and at least one non-piezoelectric layer, and wherein this piezoelectric layer is connected to non-piezoelectric layer and makes that piezoelectric layer and non-piezoelectric layer are not coextensive.Piezoelectric layer, non-piezoelectric layer or the two can be connected at least one substrate.Piezoelectric layer and non-piezoelectric layer can change on width, length and thickness.
Self-excitation self-induction type piezoelectric cantilever sensor can be used for determining the quality of the analyte that gathers on it.In example embodiment, the part of self-excitation self-induction type piezoelectric cantilever sensor is placed in the medium (for example, liquid, gas, vacuum).In the time of in being in medium, measure self-excitation self-induction type piezoelectric cantilever sensor resonant frequency and with baseline resonant frequency relatively.Measured resonant frequency and the difference table between the baseline resonant frequency are shown on the self-excitation self-induction type piezoelectric cantilever sensor and gather the quality size of the analyte of (for example, in conjunction with, absorption, absorption).
Analyte can directly or indirectly be attached to the surface of the non-piezoelectric of self-excitation self-induction type piezoelectric cantilever sensor.The combining of the non-piezoelectric of analyte and self-excitation self-induction type piezoelectric cantilever sensor cause the encouraging oneself variation of self-induction type piezoelectric cantilever sensor quality, the variation of self-excitation self-induction type piezoelectric cantilever sensor rigidity, or the two combination.For example, can measure the variation of the variation of quality and/or rigidity, and can and measure, such as exercisable amplifier, electric impedance analyzer, network analyzer, pierce circuit etc. by suitable analytical equipment monitoring as resonant frequency.Wherein the variation that is immersed in the resonant frequency in the liquid to small part self-excitation self-induction type piezoelectric cantilever sensor is detectable and measurable.Wherein the variation that is immersed in the resonant frequency in gas or the vacuum to small part self-excitation self-induction type piezoelectric cantilever sensor also is detectable and measurable.
For example, described self-excitation self-induction type piezoelectric cantilever sensor can be operated under the high frequency that such as the order of magnitude is 0.1MHz to 6MHz.Under these high frequencies, can obtain the order of magnitude under the liquid infiltration and be 10 to 100 the Q factor ratio of half-peak height place resonance peak width (formant frequency with).This self-excitation self-induction type piezoelectric cantilever sensor can be with relative high frequencies operations in liquid medium, gas medium and vacuum.Therefore this self-excitation self-induction type piezoelectric cantilever sensor provides high sensitivity to mass change.For example, this self-excitation self-induction type piezoelectric cantilever sensor is particularly suitable for being present in medium with unusual low concentration, such as the analyte in body fluid, water and the food materials.
Self-excitation self-induction type piezoelectric cantilever sensor described here provides the variation that detects the quality of gathering on it little of 100 vast gram/Hz (100 * 10 in being immersed in liquid medium the time -18Gram/hertz) or littler ability.Therefore, with respect to mass change, the sensitivity of described self-excitation self-induction type piezoelectric cantilever sensor is about 1,000,000 times of quartz crystal micro-cantilever sensor, it is about 100 of standard analysis instrument, 000 times, and be about 10,000 times of traditional three laminations electricity cantilever design.
Self-excitation self-induction type piezoelectric cantilever sensor allows to detect the analyte of the extremely low concentration that is attached to its non-piezoelectric.Use this self-excitation self-induction type piezoelectric cantilever sensor, but detectable concentration is low to moderate the pathogen and the protein of several pathogen/milliliter, and for average-size (60 kilodaltons, protein kDa), but detectable concentration is less than the pathogen and the protein of 1 pathogen/milliliter.And, can detect any analyte of the organic or inorganic functional group that is attached on the non-piezoelectric.This self-excitation self-induction type piezoelectric cantilever sensor can be operated in having the medium of relative high flow rate.This piezoelectric cantilever sensor can be operated in flow velocity is the medium of 0.5 to 10.0 ml/min, and this flow velocity is about 1000 times of success is used under the situation of known bending die micro-cantilever flow rate.
The various example application of piezoelectric cantilever comprise the terrified reagent of detection of biological, such as bacillus anthracis; Detect food-borne pathogen, such as Escherichia coli; Detect the pathogen in food and the water; Detect the particular cell types (for example circulating tumor cell) in the body fluid; Biomarker in the detection body fluid (for example, the protein of the following specific protein of mark, antigen or mark, i.e. Pathological Physiology-α-fetoprotein, β-2-microglobulin, tumor of bladder antigen, markers for breast cancer CA-15-3 and other CA (cancer antigen), calcitonin, carcinomebryonic antigen etc.); The mark that detects explosive is such as trinitro-toluene, the existence of dinitrotoluene (DNT); And detect air borne and water-borne toxin.This self-excitation self-induction type piezoelectric cantilever sensor also can be used for detecting the biosome of pik level and detects stable state and dynamic protein-protein interactions.
For example use self-excitation self-induction type piezoelectric cantilever sensor can detect such as colibacillary pathogen.Be fixed with by use self-excitation self-induction type piezoelectric cantilever sensor that target analytes is had specific antibody with about frequency of 1 to 2MHz in liquid directly measurement can realize that detectable concentration is every milliliter 1.0 femtogram (10 respectively -15Gram) model protein (model protein), lipoprotein, DNA and/or RNA and concentration are the pathogen of 1 pathogen/milliliter.Even this self-excitation self-induction type piezoelectric cantilever sensor also can detect target analytes and not have false positive and false negative when having the pollution body.Self-excitation self-induction type piezoelectric cantilever sensor described here is using crude samples, and especially favourable when not having the preparation, concentration step of any kind and/or enrichment.For example, the detection of the analyte of use self-excitation self-induction type piezoelectric cantilever sensor can be under flox condition, such as directly carrying out in crude samples under the flox condition of 0.5 to 10.0 ml/min.If can obtain blank sample, for example in laboratory environment, then can realize the detection of 1 femto grams per milliliter.This sensitivity is about 100 times of the relevant sensitivity of known optical technology.
As described below, the sensitivity of this self-excitation self-induction type piezoelectric cantilever sensor partly is because its geometry designs.The piezoelectricity of this self-excitation self-induction type piezoelectric cantilever sensor determines sensitivity with the relative length of non-piezoelectric layer and width, and the shape at the peak of the frequency spectrum that is provided by this self-excitation self-induction type piezoelectric cantilever sensor.In greater detail following, this self-excitation self-induction type piezoelectric cantilever sensor comprises that the piezoelectric layer and the non-piezoelectric layer that are linked together make the part piezoelectric layer extend beyond non-piezoelectric layer, or the non-piezoelectric layer of part extends beyond piezoelectric layer, or the combination of above two kinds of forms.Therefore, described piezoelectric layer and described non-piezoelectric layer are not coextensive.In other words, this self-excitation self-induction type piezoelectric cantilever sensor is constructed to make that the whole surface of non-piezoelectric layer is not connected to the whole surface of piezoelectric layer.
The sensitivity of self-excitation self-induction type piezoelectric cantilever sensor partly is because used the piezoelectric layer of cantilever sensor to be used to activate electromechanical property with the piezoelectric layer of sensing and this self-excitation self-induction type piezoelectric cantilever sensor.When resonance, the vibration cantilever is concentrated the stress in the piezoelectric layer towards the base part of this self-excitation self-induction type piezoelectric cantilever.This causes the variation of amplification of piezoelectric layer resistive component and the big skew of resonant frequency.Allow to utilize skew relevant in the resonant frequency to detect the minimum mass change of this self-excitation self-induction type piezoelectric cantilever sensor to the part that piezoelectric layer has low bending modulus (for example, more pliable and tougher) this stress guide.For example, if the piezoelectric layer of piezoelectric cantilever sensor (for example all is anchored on identical end with non-piezoelectric layer, be enclosed in the epoxy resin), then this sensor reduces the sensitivity of the variation of quality, because the situation of the bending stress in the sensing piezoelectric layer of contiguous anchored end during with grappling piezoelectric layer only compared low.This is because the bending modulus of the layer of two combinations is higher than the only situation of grappling piezoelectric layer.Bending modulus is elastic modulus and the moment of inertia product about neutral axis.And moment of inertia is proportional to cube power of thickness.
Fig. 1 is the key diagram that comprises the self-excitation self-induction type piezoelectric cantilever sensor 12 of piezoelectric 14 and non-piezoelectric 16.Piezoelectric indicates capitalization p (" P "), and non-piezoelectric indicates capitalization np (" NP ").That this self-excitation self-induction type piezoelectric cantilever sensor 12 has been described is grappling, that dangle, the embodiment of self-excitation self-induction type piezoelectric cantilever sensor.This self-excitation self-induction type piezoelectric cantilever sensor 12 is called " not grappling ", because non-piezoelectric layer 16 is not attached to base part 20.This self-excitation self-induction type piezoelectric cantilever sensor 12 is called " dangling ", because non-piezoelectric layer 16 extends beyond the overhang 22 of far-end 24 to form non-piezoelectric layer 16 of piezoelectric layer 14.Piezoelectric 14 is connected to non-piezoelectric 16 by adhesion section 18.Piezoelectric 14 and non-piezoelectric are overlapping in zone 23.Adhesion section 18 is between the lap of piezoelectric 14 and non-piezoelectric 16.Piezoelectric 14 is connected to base part 20.
For example, piezoelectric 14 can comprise any suitable material, such as lead zirconate titanate, lead magnesium niobate-lead titanate solid solution, strontium lead titanate, quartzy silicon, piezoelectric ceramics lead zirconate titanate (PZT), piezopolymer fibrous composite etc.For example, non-piezoelectric 16 can comprise any suitable material, such as glass, and pottery, metal, polymkeric substance, and one or more the compound substance in pottery and the polymkeric substance are such as silicon dioxide, copper, stainless steel, titanium etc.
Self-excitation self-induction type piezoelectric cantilever sensor can comprise the part with any suitable size combinations.In addition, physical size can be uneven.Therefore, piezoelectric layer and/or non-piezoelectric layer can be tapers.For example, length (for example, the L among Fig. 1 of piezoelectric (for example, piezoelectric 14) P) can be from about scope of 0.1 to about 10mm.Length (for example, the L among Fig. 1 of non-piezoelectric (for example, non-piezoelectric 16) NP) can be from about scope of 0.1 to about 10mm.The length of overlapping region (for example, the overlapping region 23) can be from about scope of 0.1 to about 10mm.Width (for example, the W among Fig. 1 of piezoelectric (for example, piezoelectric 14) P) and width (for example, the W among Fig. 1 of non-piezoelectric (for example, non-piezoelectric 16) NP) can be from about scope of 0.1 to about 4.0mm.The width of piezoelectric (for example, the W among Fig. 1 P) also can be different from width (for example, the W among Fig. 1 of non-piezoelectric NP).Thickness (for example, the T among Fig. 1 of piezoelectric (for example, piezoelectric 14) P) and thickness (for example, the T among Fig. 1 of non-piezoelectric (for example, non-piezoelectric 16) NP) can be in the scope from about 0.1mm to about 4.0mm.The thickness of piezoelectric (for example, the T among Fig. 1 P) also can be different from thickness (for example, the T among Fig. 1 of non-piezoelectric NP).
Fig. 2 describes to be used for the electrode cross-sectional view of the self-excitation self-induction type piezoelectric cantilever sensor 12 of the electrode put area 26 related with piezoelectric 14 operationally.Electrode can be placed on any suitable position on the piezoelectric of self-excitation self-induction type piezoelectric cantilever sensor shown in carriage 26.For example, as shown in Figure 3, electrode 28 can be connected to the piezoelectric 14 in the base part 20.Perhaps, as shown in Figure 4, electrode 32 can or not in the base part 20 and be not connected to piezoelectric 14 with the overlapping any position of non-piezoelectric 16.Electrode need not placed about piezoelectric 14 symmetries.In example embodiment, electrode can be connected to the piezoelectric 14 in the base part 20, and another electrode can be connected to the not piezoelectric in base part 20 14.Can use electrode or any other device (for example, induction installation, wireless device) electric signal to be provided and to receive electric signal from piezoelectric 14 to piezoelectric 14.In example embodiment, electrode can be connected to piezoelectric 14 by bonding pad (be depicted as element 30 among Fig. 3 and be depicted as element 34 in Fig. 4).The example bonding pad can comprise any suitable material (for example, gold, silicon dioxide) of the acceptor material that can fixedly be applicable to chemical sensitisation or bio-sensing and/or absorbing material.
Electrode can be placed on any suitable position.In example embodiment, electrode operationally is arranged near the concentrated position of piezoelectric layer 14 stress.As mentioned above, the sensitivity of this self-excitation self-induction type piezoelectric cantilever sensor partly is because of the stress in the piezoelectric layer 14 advantageously being led (concentrating) and electrode being placed on its vicinity.The structure of self-excitation self-induction type piezoelectric cantilever sensor described here (with its various variations) is tending towards concentrating the relevant stress of vibration in the piezoelectric layer 14.When resonance, in the structure of some self-excitation self-induction type piezoelectric cantilever sensor, the vibration cantilever is concentrated the stress in the piezoelectric layer 14 towards base part 20.This causes in the variation of the amplification of high stress locations piezoelectric layer 14 resistive components and the big skew of resonant frequency.This stress is directed to the part that piezoelectric layer 14 has low bending modulus (for example, more pliable and tougher) allows to utilize relevant resonant frequency shift to detect the minimum mass change of this self-excitation self-induction type piezoelectric cantilever sensor.Therefore, in the example constructions of this self-excitation self-induction type piezoelectric cantilever sensor, the thickness that is positioned near the piezoelectric layer 14 the base part 20 is thinner than the part of piezoelectric layer 14 further from base part 20.This is tending towards stress in the thin segment set of piezoelectric layer 14.In example constructions, electrode is positioned near the relevant stress of vibration is concentrated the base part of this self-excitation self-induction type piezoelectric cantilever sensor position or near this position.In another example embodiment of self-excitation self-induction type piezoelectric cantilever sensor, no matter the base part whether stress of concentrating is close to this self-excitation self-induction type piezoelectric cantilever sensor, it is contiguous that electrode all is arranged in piezoelectric layer stress concentrated position.
Self-excitation self-induction type piezoelectric cantilever sensor can be constructed according to multiple structure, and some in these structures are shown among Fig. 5 to Figure 16.Yet should be understood that structure described herein do not represent all possible structure, but the representative illustration of structure that should self-excitation self-induction type piezoelectric cantilever sensor.Fig. 5 is the key diagram of example constructions 36 of the self-excitation self-induction type piezoelectric cantilever sensor of not grappling, and wherein the far-end 40 of piezoelectric 14 flushes with the far-end 38 of non-piezoelectric 16.It is because non-piezoelectric 36 is not attached to base part 20 that this self-excitation self-induction type piezoelectric cantilever sensor 36 is called as " not grappling ".Piezoelectric 14 is connected to non-piezoelectric 16 by adhesion section 18.Adhesion section 18 is between the lap of piezoelectric 14 and non-piezoelectric 16.Piezoelectric 14 is connected to base part 20.
Fig. 6 is the key diagram of example constructions 42 of the self-excitation self-induction type piezoelectric cantilever sensor of not grappling, and wherein the far-end 44 of piezoelectric 14 near-end 43 that extends beyond the far-end 46 of non-piezoelectric 16 and piezoelectric 14 extends beyond the near-end 45 of non-piezoelectric 16.Piezoelectric 14 is connected to non-piezoelectric 16 by adhesion section 18.Adhesion section 18 is between the lap of piezoelectric 14 and non-piezoelectric 16.Piezoelectric 14 is connected to base part 20.
Self-excitation self-induction type piezoelectric cantilever sensor can also be configured to comprise a plurality of base part.The example constructions that comprises the self-excitation self-induction type piezoelectric cantilever sensor of a plurality of base part is shown among Fig. 7 to Figure 14.Self-excitation self-induction type piezoelectric cantilever sensor is configured to comprise that a plurality of base part are not the schemes of intuition, because being the two ends of fixing self-excitation self-induction type piezoelectric cantilever sensor, those of ordinary skill in the art's idea will provide poor response, because it is limited to be fixed to cause the encouraging oneself displacement of self-induction type piezoelectric cantilever sensor of a plurality of basal part branch.For the structure of the self-excitation self-induction type piezoelectric cantilever sensor that comprises two base part, in example embodiment, measure the stress in the piezoelectric, rather than the displacement of piezoelectric.The self-induction type piezoelectric cantilever sensor of will encouraging oneself is configured to comprise that two base part provide stable and reliable sensors, and this sensor can move and provide excellent mass change sensitivity under high relatively media flow condition.Except the following self-induction type piezoelectric cantilever sensor of mechanically encouraging oneself reliably is provided, promptly this sensor can bear beyond the media flow condition of relative wide region in minimum performance measurement, self-excitation self-induction type piezoelectric cantilever sensor is configured to comprise that two base part also provide than having the similar cantilever sensor Senior Two of single base part and size doubly to three times fundamental frequency (for example, greater than 100kHz).
Fig. 7 is the key diagram of example constructions 48 of self-excitation self-induction type piezoelectric cantilever sensor that comprises the grappling of two base part 20,50.It is because non-piezoelectric 16 is attached to base part 20 that this self-excitation self-induction type piezoelectric cantilever sensor 48 is called as " grappling ".In the structure of describing in this self-excitation self-induction type piezoelectric cantilever sensor 48, the near-end 52 of piezoelectric 14 and the near-end 54 of non-piezoelectric 16 all are attached to substrate 20.Piezoelectric and non-piezoelectric can be attached to base part by any proper device.The far-end 58 of non-piezoelectric 16 also is attached to base part 50.The far-end 58 of non-piezoelectric 16 extends beyond the distal portions 56 of piezoelectric 14.Piezoelectric 14 is connected to non-piezoelectric 16 by adhesion section 18.Adhesion section 18 is between the lap of piezoelectric 14 and non-piezoelectric 16.
Fig. 8 is the key diagram of example constructions 60 of self-excitation self-induction type piezoelectric cantilever sensor that comprises the grappling of two base part 20,50, and wherein piezoelectric 14 is not attached to base part 20 or base part 50.In the structure of describing in this self-excitation self-induction type piezoelectric cantilever sensor 60, the far-end 64 that the near-end 62 of non-piezoelectric 16 is attached to substrate 20 and non-piezoelectric 16 is attached to base part 50.The far-end 64 that the near-end 62 of non-piezoelectric 16 extends beyond the near-end 66 of piezoelectric 14 and non-piezoelectric 16 extends beyond the far-end 68 of piezoelectric 14.Piezoelectric 14 is connected to non-piezoelectric 16 by adhesion section 18.Adhesion section 18 is between the lap of piezoelectric 14 and non-piezoelectric 16.
Fig. 9 is the key diagram of example constructions 70 of the self-excitation self-induction type piezoelectric cantilever sensor of following grappling, wherein said self-excitation self-induction type piezoelectric cantilever sensor comprises two base part 20,50, comprise two piezoelectric 14,17, and comprise two adhesion sections 18,74.In the structure of describing in this self-excitation self-induction type piezoelectric cantilever sensor 70, the near-end 76 of piezoelectric 14 and the near-end 78 of non-piezoelectric 16 are attached to base part 20.The far-end 80 of piezoelectric 72 and the far-end 82 of non-piezoelectric 16 are attached to base part 50.The near-end 78 of non-piezoelectric 16 extends beyond the near-end 86 of piezoelectric 72.The far-end 82 of non-piezoelectric 16 extends beyond the far-end 84 of piezoelectric 14.The far-end 84 of piezoelectric 14 and the near-end 86 of piezoelectric 72 form interval 88 between them.Piezoelectric 14 is connected to non-piezoelectric 16 by adhesion section 18.Piezoelectric 72 is connected to non-piezoelectric 16 by adhesion section 74.Adhesion section 18 and 74 lays respectively at the lap of piezoelectric 14 and non-piezoelectric 16, and between the lap of piezoelectric 72 and non-piezoelectric 16.
In the various alternative example constructions of the structure shown in Fig. 9 70, only there is one to be attached to each base part 20,50 in the piezoelectric 14,72.For example, in an example constructions as shown in Figure 10, piezoelectric 14 is attached to base part 20 and piezoelectric 72 is not attached to base part 50.In another example constructions as shown in Figure 11, piezoelectric 72 is attached to base part 50 and piezoelectric 14 is not attached to base part 20.In another example constructions as shown in Figure 12, piezoelectric 14 and piezoelectric 72 all are not attached to each base part 20,50.Piezoelectric layer comprises that in the various example constructions of a plurality of parts, electrode can be attached to any suitable piezoelectric therein.For example, in the example constructions shown in Fig. 9, Figure 10, Figure 11 and Figure 12, electrode can be attached to piezoelectric 14, piezoelectric 72 or both combinations.
Figure 13 is the key diagram of example constructions 90 of self-excitation self-induction type piezoelectric cantilever sensor that comprises the grappling of two base part 20,50, and wherein piezoelectric 14 is attached to base part 20 and non-piezoelectric 16 is attached to base part 50.Piezoelectric 14 is connected to non-piezoelectric 16 by adhesion section 18.Adhesion section 18 is between the lap of piezoelectric 14 and non-piezoelectric 16.The far-end 98 of non-piezoelectric 16 extends beyond the far-end 96 of piezoelectric 14.The near-end 92 of piezoelectric 14 extends beyond the near-end 94 of non-piezoelectric 16.
Figure 14 is the key diagram of example constructions 100 of self-excitation self-induction type piezoelectric cantilever sensor that comprises the grappling of two base part 20,50, and wherein non-piezoelectric 16 is not attached to base part 20 or base part 50.In the structure shown in this self-excitation self-induction type piezoelectric cantilever sensor 100, the far-end 104 that the near-end 102 of piezoelectric 14 is attached to base part 20 and piezoelectric 14 is attached to base part 50.The far-end 104 that the near-end 102 of piezoelectric 14 extends beyond the near-end 106 of non-piezoelectric 16 and piezoelectric 14 extends beyond the far-end 108 of non-piezoelectric 16.Piezoelectric 14 is connected to non-piezoelectric 16 by adhesion section 18.Adhesion section 18 is between the lap of piezoelectric 14 and non-piezoelectric 16.
Figure 15 is the key diagram of example constructions 110 of self-excitation self-induction type piezoelectric cantilever sensor that comprises the not grappling of piezoelectric 14 and non-piezoelectric 16, the wherein width W of piezoelectric PWidth W less than non-piezoelectric 16 NPStructure 110 shown in Figure 15 is similar to the structure 12 shown in Fig. 1, and difference is W PLess than W NPTherefore, this self-excitation self-induction type piezoelectric cantilever sensor 110 has been described the not embodiment of the self-excitation self-induction type piezoelectric cantilever sensor that dangles of grappling.Piezoelectric 14 is connected to non-piezoelectric 16 by adhesion section (adhesion section not shown in Figure 15).This adhesion section is between the lap of piezoelectric 14 and non-piezoelectric 16.Piezoelectric 14 is connected to base part 20.
Figure 16 is the key diagram of example constructions 112 of self-excitation self-induction type piezoelectric cantilever sensor that comprises the not grappling of piezoelectric 14 and non-piezoelectric 16, the wherein width W of piezoelectric PWidth W less than non-piezoelectric 16 NP, and wherein the far-end 114 of piezoelectric 14 near-end 118 that extends beyond the far-end 116 of non-piezoelectric 16 and piezoelectric 14 extends beyond the near-end 120 of non-piezoelectric 16.Structure 112 shown in Figure 16 is similar to the structure 42 shown in Fig. 6, and difference is W PLess than W NPPiezoelectric 14 is connected to non-piezoelectric 16 by adhesion section (adhesion section not shown in Figure 16).This adhesion section is between the lap of piezoelectric 14 and non-piezoelectric 16.Piezoelectric 14 is connected to base part 20.
Figure 17 is to use the process flow diagram of the instantiation procedure of self-excitation self-induction type piezoelectric cantilever sensor check and analysis thing.This self-excitation self-induction type piezoelectric cantilever sensor is provided in step 120.This self-excitation self-induction type piezoelectric cantilever sensor can be constructed according to the above description that provides, or according to its any suitable varied configurations.In step 122, prepare this self-excitation self-induction type piezoelectric cantilever sensor and come the receiving and analyzing thing.In example embodiment, the analyte attractor is applied to the non-piezoelectric of this self-excitation self-induction type piezoelectric cantilever sensor.This attractor is specific to analyte.This attractor attracts target analytes and does not attract other material.For example, the non-piezoelectric of this self-excitation self-induction type piezoelectric cantilever sensor can comprise, attract following attractor: such as the bio-terrorism reagent of bacillus anthracis, such as Escherichia coli, the food-borne pathogen of the pathogen in food and the water, cell type in the body fluid (for example circulating tumor cell), biomarker in the body fluid (for example, Pathological Physiology-α-fetoprotein that mark is specific, β-2-microglobulin, tumor of bladder antigen, markers for breast cancer CA-15-3, with other CA (cancer antigen), calcitonin, carcinomebryonic antigen etc.), such as trinitro-toluene, the mark of the explosive of dinitrotoluene (DNT), air borne and water-borne toxin, such as the biosome of protein, or above-mentioned combination.
Be exposed to medium at the step 124 self-induction type piezoelectric cantilever sensor of should encouraging oneself.For example, this medium can comprise any suitable medium, such as the combination or the vacuum of liquid, gas, liquids and gases.This medium can demonstrate a variety of flox conditions.If target analytes is present in the medium, then target analytes will accumulate on the non-piezoelectric of the self-excitation self-induction type piezoelectric cantilever sensor of handling with attractor.As mentioned above, target analytes (for example gathering on the non-piezoelectric of this self-excitation self-induction type piezoelectric cantilever sensor, in conjunction with) will cause the stiffness variation of this self-excitation self-induction type piezoelectric cantilever sensor and/or the quality of this self-excitation self-induction type piezoelectric cantilever sensor to increase, this will reduce the resonant frequency of this self-excitation self-induction type piezoelectric cantilever sensor.
Measure the resonant frequency of this self-excitation self-induction type piezoelectric cantilever sensor in step 126.Can measure resonant frequency as exercisable amplifier, electric impedance analyzer, network analyzer, pierce circuit etc. by for example any proper device.When the piezoelectric of the piezoelectric of this self-excitation self-induction type piezoelectric cantilever sensor was subjected to encouraging, the non-piezoelectric bending of this self-excitation self-induction type piezoelectric cantilever sensor was to adapt to the strain that causes in piezoelectric.When the natural frequency of the frequency of excitation and following physical construction is identical, resonate.
In step 128 resonant frequency and the baseline resonant frequency of measuring compared.Baseline resonant frequency is not gather the resonant frequency of the self-excitation self-induction type piezoelectric cantilever sensor of analyte on it.If do not record the resonant frequency and the difference on the frequency between the baseline resonant frequency (frequency displacement) (in step 130) of measurement, then determine not detect analyte in step 132.If record the resonant frequency and the difference on the frequency between the baseline resonant frequency (frequency displacement) (in step 130) of measurement, then determine to detect analyte in step 134, promptly in medium, there is analyte.In step 136, the size of the quality of the analyte that gathers is determined in the frequency displacement that records according to step 130 on the non-piezoelectric of self-excitation self-induction type piezoelectric cantilever sensor.
Used the various structures of this self-excitation self-induction type piezoelectric cantilever sensor to carry out various experiments.Figure 18 is Figure 137 of example resonance spectrum of the structure 12 of the self-excitation self-induction type piezoelectric cantilever sensor operated in air.Width W PAnd width W NPBe about 2mm respectively.Figure 137 has shown at (between driving voltage and the exciting current) phase angle under the driving voltage of 100mV with respect to the relation of excitation frequency.The first resonant frequency mould 140 approximately occur in 150 and 200kHz between and the second resonant frequency mould 142 occur in 250 and 300kHz between.Resonance spectrum demonstrates higher characteristic peak under about 980kHz, 2.90MHz and 4.60MHz.
Quality factor are confirmed as the ratio of resonant frequency with respect to half-peak height place peak width.Therefore, quality factor are the tolerance of resonance peak acutance.Experiment has shown that when sensor is placed on from the varying environment of vacuum in the liquid flow environmental field quality factor of this self-excitation self-induction type piezoelectric cantilever sensor all significantly do not reduce.And experiment has shown that the Q value of various structures of this self-excitation self-induction type piezoelectric cantilever sensor depends on each frequency mould of detecting the peak and common in 10 to 70 scope.The various structures of this self-excitation self-induction type piezoelectric cantilever sensor, when at vacuum, air and viscosity environment, comprise that when using in the fluid, the decline of Q value is no more than 20～35% usually.In whole values of quality factor relatively little loss reflected this self-excitation self-induction type piezoelectric cantilever sensor at the viscosity environment, comprise in water and the blood flow the accurately ability of detection of chemicals and various biological product.
Experiment has shown that the sensitivity of self-excitation self-induction type piezoelectric cantilever sensor is the function of its size.The specific change of the geometry of self-excitation self-induction type piezoelectric cantilever sensor has strengthened the mass change sensitivity of this sensor, and therefore strengthens this sensor to detecting the response of analytes in low concentration.Resonance spectrum, i.e. phase angle illustrating in air to excitation frequency 102 ± 0.05,970 ± 0.05 and the principal curvature mould resonance peak at 1810 ± 0.05kHz place.By changing the geometric configuration of this self-excitation self-induction type piezoelectric cantilever sensor, strengthened the resonance characteristics of sensor.Corresponding flexural resonance mould occurs under the higher frequency and has bigger phase angle, shows that the resonance peak of this self-excitation self-induction type piezoelectric cantilever sensor is sensitiveer and damping is littler.
In example experiment, measure the mass change of self-excitation self-induction type piezoelectric cantilever sensor.The paraffin of known quality is added to the glass surface of this self-excitation self-induction type piezoelectric cantilever sensor and uses the change calculations mass sensitivity of resonant frequency, represent with g/Hz.Directly measure the mass change sensitivity in liquid; And the ratio of known quality and variation of resonant frequency in liquid before and after the increase quality.The mass sensitivity of determining the resonant mode of research under the liquid is 1.5 * 10 -15G/Hz.
Piezoelectric cantilever sensor detects the application of airborne analyte
The applicant has been found that and detect the relevant undocumented information of target analytes in gas phase.The present invention has solved the detection of target analytes in the gas phase by the identification body that analyte is attached in the sensor.This identification body demonstrates the affinity to target analytes.The example of bio-identification body comprises polyclone and monoclonal antibody, single-chain antibody (scFv), adaptive son (for detecting the synthetic DNA of the special exploitation of target molecule), reorganization and natural bacteriophage etc.In one embodiment, when using such as frequency transducing method described here, the fixing antibody of detecting device utilization detects the concentration of airborne analyte as the identification body.Fixing antibody is the lip-deep antibody that is attached to the sensor that is used for the air borne detection as the identification body.Such air borne detects to be provided such as pathogen, comprises the biological substance of bacterium, virus, egg capsule, Puli's protein and spore and detects such as the accurate fast of abitotic substance of chemicals.But detection of biological threatens, such as bacterium, spore etc.; And the chemistry threat, such as explosivity or toxic chemical.
In one aspect of the invention, as mentioned above, the detection of air borne analyte of using the identification body be by will having the sensor of identification body, be exposed to airflow and carry out such as the coated surfaces of sensor.This airflow can contain or not contain analyte.If airflow does not contain analyte, then estimate to detect less than.Yet if analyte is present in the airflow, this analyte is attached to the identification body and influences the characteristic of sensor.The characteristic of this change can detect by enough transducers, and this transducer detects the existence of the analyte that is attached to sensor now.Particularly, transducer mechanism can be passed through optics, frequency, electric capacity, conductivity, bending die or the operation of static schema cantilever.This transducer mechanism can be determined the variation by analyte sensor characteristic of causing with combining of body of identification.As a result, can detect and quantize the characteristic (that is, size, frequency, quality, electric capacity, conductivity, bending die etc.) of this change.In case quantize, just can use the known calculation element of those skilled in the art, determine to be attached to the amount of the analyte of discerning body such as computing machine, flush bonding processor or digital circuit or mimic channel.A kind of such transducer mechanism is following frequency, and wherein the mechanical resonance of sensor is attached to the identified surface of sensor along with analyte and changes.The example embodiment of frequency of utilization transducing provides below.Yet other energy converter also is possible as mentioned above.
At an embodiment who is used for detecting the frequency inverted of airborne analyte, the inventor finds that cantilever (PEMC) sensor of the mm size of piezoelectric excitation is because their high sensitivity and can be used to detect airborne material.With the identification body, can respond the analyte that is set as target such as the PEMC of antibody or dna molecular preparation is surperficial, described target analytes can be pathogen, protein or biomolecule.This situation causes the variation of cantilever quality, and the variation of cantilever quality shows as variation of resonant frequency and can monitor by suitable analyser.Suitable analyser can comprise lock-in amplifier, electric impedance analyzer, network analyzer or even pierce circuit.
In this application, a kind of technology that is used to detect airborne pathogen has been described.Aspect comprises the method that airborne target organism or molecule are contacted with the PEMC sensor, and this PEMC sensor comprises identification molecule existing with sensed object organism or molecule.An advantage of the present invention is that this can carry out not needing target organism or molecule be collected under the situation that is used for sensing in the liquid medium.Traditional method is placed on sensor in the liquid environment.The attached of unwanted particulate pollutant resisted on known dynamic sensitive surface such as the vibration surface.Since the PEMC sensor with vibration when air-flow contact, therefore only can take place chemically combined attached, thereby reduce or eliminate the false positive that the particulate pollutant by gas propagation in the airflow sample causes.This principle becomes advantage of the present invention because the PEMC sensor can provide the specificity of context of detection with the thing that decontaminates by their operation.
In one embodiment of the invention, stipulated that sensor surface is with respect to the position and/or the orientation of flow air stream in the low speed flow region.Preferably, use about 0.01 speed air flow to detect to about 30 meter per seconds.The low speed flow region increases the duration of contact that is used to combine between target substance and the sensor surface.Can also strengthen the duration of contact between target substance and the sensor surface by ad-hoc location or the orientation of sensor surface with respect to airflow.Preferably, sensor surface and airflow are orientated substantially orthogonally, although other orientation also is possible.The binding affinity of the antigen of spore to the sensor can depend on local humidity.Provide the value of sufficient combination and 95% that excellent binding affinity is provided humidity 10 to 95% the scope of remaining on.Though in 0.01 to 30m/s flow rates, observe combination, this scope demonstrate higher binding kinetics than the lower end.In certain embodiments, the airflow speed of 0.01 to 10 meter per second is acceptable speed.
Confirmed method of the present invention can under the concentration that is low to moderate 40 spores of every litres of air, detect anthrax spores when in air, directly measuring and do not needed to prepare sample based on liquid or gel-in-matrix.
Figure 19 A-19G has shown the embodiment of the various piezoelectric cantilever sensors that can use in the methods of the invention.Should notice that figure of the present invention does not except as otherwise noted all draw in proportion, and these figure illustrate conceptually.In Figure 19 A-19G, each sensor is made of piezoelectric layer 14 (being designated as P), adhesion layer 18 (between the lap of piezoelectric layer and non-piezoelectric layer) and non-piezoelectric layer 16 (being designated as NP), and this non-piezoelectric layer comprises the part of extending as terminal.Substrate 20 is attached places of piezoelectric layer 14.Substrate 20 has electrode (not shown) or other similar device usually, and similarly device and substrate 20 are related is used to be connected to piezoelectric layer 14 for described electrode or other, are connected to piezoelectric layer 14 although need only electrode, and then electrode does not need related with substrate 20.Electrode can be placed on any position on the piezoelectric layer 14.Bonding pad can also be arranged, and this bonding pad is by gold, SiO 2, can sessile receptor the material of material, and/or the absorbing material that is suitable for using in chemical sensitisation or bio-sensing is made.Those skilled in the art will recognize the design described in Figure 19 A-19G and only be the subclass of possible geometric configuration.Therefore, the variation scheme of these designs is in the application's scope.For example, the non-piezoelectric of sensor whole width or its part that can stride across piezoelectric layer is attached to piezoelectric layer with perhaps many dispersed numbers.
Cantilever or beam (simple or compound) sensor is mechanically vibrated by the AC electric excitation of PZT layer.When excitation frequency was consistent with mechanical resonance frequency or its high-order mode, vibration amplitude (from departing from of balance) was than lower or upper frequency is bigger.Therefore compare the higher stress level of PZT experience when resonance with the level that shows when the off-resonance frequency.Stress level among the PZT changes along its length, and depends on the vibration shape.The vibration shape depends on the bending modulus of cantilever again.For example, with reference to Figure 19 A, partly locate much higher than S in the bending modulus that R partly locates.The position of exciting electrode solder joint is in the higher stress position or be favourable because it gives bigger signal during by impedance bioelectrical measurement near it.The sensitivity of free end cantilever or beam sensor is higher under higher resonant frequency.Various example structure shown in Figure 19 A-19G and Figure 35-46 are designed to realize main high-order resonant mode in the scope of 60kHz to 6kHz.The Position Design of the non-piezoelectric layer that disperses can be strengthened specific high-order mode for making, and reduce the intensity of non-bending die.
Piezoelectric layer 14 can be constructed by following material: lead zirconate titanate, lead magnesium niobate-lead titanate solid solution, strontium lead titanate, quartzy silicon, piezoelectric ceramics lead zirconate titanate (PZT) or piezopolymer 1-3 fibrous composite.Non-piezoelectric layer 16 can be constructed by following material: pottery, and metal, the compound substance of one or more in polymkeric substance and pottery, metal and the polymkeric substance is such as silicon dioxide, copper, stainless steel and titanium etc.Be used for all can be used for constructing non-piezoelectric layer in any known materials that the non-piezoelectric layer of constructing the conventional piezoelectric cantilever uses.Electrode can be any suitable, traditional electrode.In one embodiment, depend on the exposed environments of various piezoelectric cantilever sensors, electrode can be insulation or on-insulated.
Compare with definite frequency displacement with baseline vibration (resonant frequency) by vibration (that is the resonant frequency) vibration (resonant frequency) of measuring and will measure and to finish detection device.The frequency displacement that should determine can be used for determining being attached to the existence of the analyte of identification body then, and this identification body is deposited on the piezoelectric layer of sensor or non-piezoelectric layer on one of them.The combination of piezoelectric layer, non-piezoelectric layer and identification body comprises cantilever, and this cantilever vibrates by the electrode excitation that is attached to piezoelectric layer the time.
One aspect of the present invention is the apparatus and method that are used to measure any analyte that can directly or indirectly be attached to the surface.The combination of analyte causes mass change or stiffness variation or both all to change.These variations can be used as the variation of resonant frequency and measure, and can be by suitable analytical equipment monitoring, such as lock-in amplifier, electric impedance analyzer, network analyzer or pierce circuit.Embodiments of the invention comprise the new geometry designs of piezoelectric cantilever.The non-piezoelectric layer that traditional piezoelectric cantilever is attached to piezoelectric layer on the whole surface that is positioned at piezoelectric layer is made.In some traditional piezoelectric cantilever, piezoelectric layer one end is fixing to make that non-piezoelectric layer bending is to adapt to the strain that causes in the piezoelectric when piezoelectric is subjected to encouraging.When the natural frequency of the frequency of excitation and following physical construction is identical, resonate.Such cantilever sensor the time is good with the frequency operation that is lower than about 100kHz under mm size.Higher frequency only can by make cantilever lack very much (less than 1mm) just possible.
Another form of conventional piezoelectric cantilever comprises the unfixed piezoelectric of an end.Here it is so-called " the not piezoelectric cantilever of grappling ".This not the piezoelectric cantilever of grappling when surpassing 100kHz, show its first bending die resonance, and conventional grappling cantilever shows their first bending die resonance when 2-60kHz.Second bending die resonance is usually located at the scope of 200kHz, and high-order mode appears at 400kHz, 800kHz and frequency that may be higher.
Presenting any mould that is higher than 10 Q value all is easily in actual sensing.The Q value is the ratio of formant frequency with respect to half-peak height place resonance peak width.Yet the not all mould that high Q value is shown all provides sensitive detection.Between the empty G﹠W and the difference of the resonant frequency between air and the vacuum provided measuring of sensitivity because the difference of density causes the frequency displacement of resonant frequency.In many piezoelectric cantilever sensors, depend on the geometry in particular of sensor, the variation of medium from the air to the vacuum causes variation of resonant frequency 4 to 25kHz.
The relative length of piezoelectric layer and non-piezoelectric layer and width are determined sensitivity and the peak shape of the frequency spectrum that provided by sensor.This can find out from the spectrum of the various piezoelectric cantilever sensors that comprise as accompanying drawing here.
The present invention allows to detect the analyte of the minimum concentration that will be attached to the piezoelectric cantilever surface.In example, confirmed in air the pathogen of low concentration and the detection of protein.And, can detect any analyte that will be attached to the lip-deep organic or inorganic of PEMC functional group.Therefore, use equipment can in airborne environment, detect chemistry and biological reagent based on PEMC.
There are various potential application in cantilever of the present invention, such as the terrified reagent of detection of biological, such as bacillus anthracis, detect airborne pathogen, detect mark such as the explosive of trinitro-toluene, such as the existence of dinitrotoluene (DNT), and detect airborne toxin.Piezoelectric cantilever of the present invention also is used in pik horizontal detection biosome and detects stable state and dynamic protein-protein interaction.
As example application, exist specific immersion coating is had the inorganic matter of high-affinity, and therefore airborne analyte sensor, can be used in abiotic application such as PEMC or PEMCB sensor, such as detecting poisonous or explosive chemicals.For example, as poly-(1-(4-hydroxyl-4-trifluoromethyl-5,5,5-trifluoro) penta-1-thiazolinyl) methyl-monosilane of aSXFA-[of identification body] polymer coating can be used for detecting 2,4-dinitrotoluene (DNT) (DNT).And, can be used for detecting explosive such as trinitro-toluene (TNT) and explosive label such as 2 as the molecularly imprinted polymer (MIP) of identification body, and the 4-dinitrotoluene (DNT) (2,4-DNT).
Figure 19 A has shown the not embodiment 710 of the piezoelectric cantilever sensor that dangles (oPEMC) of grappling.It is because non-piezoelectric layer 16 is not attached to substrate that this sensor 710 is called " not grappling ".This scales is that this overhang separates by overlapping region 18 and piezoelectric layer because the far-end that non-piezoelectric layer 16 extends beyond piezoelectric layer 14 is to form the overhang of non-piezoelectric layer 16 for " dangling ".Substrate 20 is used for fixing the near-end of piezoelectric layer 14.
The sensor of the part with all suitable dimensions is contained in the present invention.For example, the length of each of piezoelectric layer 14, non-piezoelectric layer 16 and overlapping region 18 can be in 0.1 to 10mm scope.For above-mentioned given length, the width of piezoelectric layer 14 and non-piezoelectric layer 16 can be in the scope of 0.1mm to 4mm.The width of piezoelectric layer 14 also can be different from the width of non-piezoelectric layer 16.
Usually, the piezoelectric cantilever sensor 710 that dangles has length and about 0.1mm non-piezoelectric layer 16 of the width between about 4.0mm extremely of about 0.1mm between about 10.0mm.Piezoelectric layer 14 can be about 0.1mm to about 10.0mm, and perhaps wide about 0.25 to about 4.0mm.Layer 18 is corresponding to overlapping between 16 of layer 14 and layer, and depends on that the particular configuration of the piezoelectric cantilever sensor that dangles can be about 0.1mm to about 10.0mm, perhaps is about 0.1 to about 5.0mm.
The width of piezoelectric cantilever 710 sensors that dangle can be about 0.1mm to about 4.0mm.The thickness of this piezoelectric cantilever 710 can be about 0.1mm to about 1.0mm.The table 1 of Figure 47 has been showed several example sizes corresponding to the PEMC equipment that dangles of Figure 19 A.In the table 1 of Figure 47, corresponding among length dimension a, b and c and Figure 19 A.
The piezoelectric cantilever sensor that dangles 710 of the present invention shows the first bending die resonant frequency mould peak at 10-120kHz usually, and shows the second bending die resonant frequency mould peak at 120kHz-250kHz.
Figure 19 B-19F has shown the various embodiment according to the cantilever beam sensor of piezoelectric excitation of the present invention, has confirmed that they also provide the sensing response of success.Described cantilever beam sensor comprises the whole components identical of the sensor that dangles with Figure 19 A, but also comprises second substrate 50, and at least one in piezoelectric layer 14 and the non-piezoelectric layer 16 also is fixed to this substrate 50.In Figure 19 B-19D, non-piezoelectric layer 16 is fixed to two substrates (20,50) to form " beam ".In Figure 19 E, described beam forms by following method, is about to piezoelectric layer 14 and is fixed to substrate 20, non-piezoelectric layer 16 is fixed to piezoelectric layer 14 and non-piezoelectric layer 16 is fixed to substrate 50 by adhesion layer 18.In the structure 717 of Figure 19 F, described beam forms by piezoelectric layer 14 is fixed to two substrates (20,50).
The grappling at the two ends of piezoelectric layer and non-piezoelectric layer uses 3mm glass or tungsten bar to finish.As long as the bending modulus of support stick much larger than sensor beam, is then observed excellent peak shape.Also can adopt other suitable anchorage method.
The design of the cantilever beam sensor of Figure 19 B-19F is not the design of intuition, because those of ordinary skill in the art's meeting wishes that the two ends of fixed beam will provide poor response, can cause the displacement of cantilever limited because be fixed to substrate (20,50).In other words, in the cantilever of prior art, an end of cantilever is a free end,, is not fixed to substrate that is, allowing cantilever bigger displacement in the process of sensing, thus the response that improves sensor.
Figure 19 G has described the alternate embodiment 719 of the overhanging form of Figure 19 A, and it is called as unmanaged flexibility end PEMC (ftPEMC) sensor.Different with the sensor among Figure 19 B-19F, it is attached that the structure of Figure 19 G only has a substrate 20.The execution result of this structure and other structure is further described below.
Get back to two substrates (20,50) " beam " structure of Figure 19 B-19F, found to measure the stress in the piezoelectric layer, rather than the displacement of piezoelectric layer, allow to use the cantilever two ends all to be fixed to cantilever " beam " sensor of substrate (20,50).In addition, cantilever beam sensor of the present invention provides higher basic mode (〉 100kHz), the reliable and stable performance under the flox condition and excellent mass change sensitivity, it allows hang down the sample concentration detection.
An advantage of the present invention is that the design of above Figure 19 A-19G is mechanically reliable and stands flox condition performance degradation minimum simultaneously.Second advantage is that fundamental frequency is the three to four-fold of the similar sensor of size in the cantilevered construction.
Figure 20 that is discussed below-31 has shown the various result of experiment of using the different embodiment according to cantilever (oPEMC) sensor of the mm size of the piezoelectric excitation that dangles of the present invention to carry out.The table 1 of Figure 47 has provided the size and the resonant frequency of PEMC (oPEMC) equipment that dangles.Fig. 2 has shown the typical resonance spectrum (referring to the oPEMC#1 of Figure 47 table 1) of first embodiment of the piezoelectric cantilever sensor of operating that dangles as shown in Figure 19 A in air.Phase angle is shown in Fig. 2 to the curve map of excitation frequency under the driving voltage of 100mV.The first resonant frequency mould appears between 150 to 200kHz usually, and the second resonant frequency mould appears between 250 to 300kHz.Resonance spectrum shows the composite PZT cantilever for wide 2mm, and the high-order mode characteristic peak is positioned at about 980kHz, 2.90MHz and 4.60MHz place.With similarly not the piezoelectric cantilever structure that dangles of the nothing of grappling compare, it is more stable a little and most of viewed resonant frequency is higher to be up to the baseline of 5MHz.In addition, the quality factor of 980kHz characteristic peak (Q) are three times of embodiment of dangling, and the quality factor of 4.60MHz characteristic peak (Q) are 1/2nd.
Figure 21 has shown the typical resonance spectrum (referring to the oPEMC#2 of Figure 47 table 1) of second embodiment of the piezoelectric cantilever sensor of operating that dangles shown in Figure 19 A in air.Figure 21 has shown that phase angle is to the curve map of excitation frequency under the 100mV driving voltage.The first resonant frequency mould appears between 150 to 200kHz usually, and the second resonant frequency mould appears between 250 to 300kHz.The resonance spectrum of second embodiment of the piezoelectric cantilever sensor that dangles shows the composite PZT cantilever for wide 2mm, and the high-order mode characteristic peak is positioned at about 980kHz, 2.90MHz and 4.60MHz.The overhang of this embodiment of the piezoelectric cantilever sensor that this dangles, promptly the zone 16 of Figure 19 A is three times of overhang of oPEMC#1, some decay that this may cause the first resonant frequency mould and appear at the resonant frequency mould between 850 to 900kHz.
Figure 22 has shown the resonance spectrum (referring to the oPEMC#3 of Figure 47 table 1) of the 3rd embodiment of the piezoelectric cantilever sensor of operating that dangles in air.Figure 22 has shown that phase angle is to the curve map of excitation frequency under the 100mV driving voltage.The first resonant frequency mould appears between 150 to 200kHz usually, and does not have the tangible second resonant frequency mould.The resonance spectrum of this embodiment of the piezoelectric cantilever sensor that this dangles shows the composite PZT cantilever for wide 1mm, and the high-order mode characteristic peak is positioned at about 1.81MHz and 1.95MHz place.Compare with the structure that the nothing of not grappling is dangled, the resonance peak of this pendant formation at the 1.81MHz place becomes obviously, and weakened above all other peaks of 2.5MHz.
Figure 23 has shown according to the resonance spectrum of the 4th embodiment of the piezoelectric cantilever that dangles of the present invention (referring to the oPEMC#4 of Figure 47 table 1).The resonance spectrum of Figure 23 uses the wide cantilever that the dangles acquisition of 1mm that has by the piezoelectric layer of ceramic PZT structure.This spectrum is used 100mV signal excitation cantilever and is obtained in air.Obtain characteristic peak at 250kHz, 650kHz, 850kHz, 1.65MHz and 4.65MHz place.
Figure 24 has shown according to the resonance spectrum of the 5th embodiment of the piezoelectric cantilever that dangles of the present invention (referring to the oPEMC#5 of Figure 47 table 1).Use has the resonance spectrum that is formed Figure 24 by the wide cantilever that dangles of 1mm of the piezoelectric layer of ceramic PZT structure.By shortening the part (a) of cantilever, whole listed frequencies are obtained the peak of more decay.This spectrum is used 100mV signal excitation cantilever and is obtained in air.Obtain characteristic peak at 200kHz, 1.0MHz, 1.55MHz, 1.90MHz and 4.50MHz place.In addition, the size of the piezoelectric cantilever that dangles among this embodiment causes sensitive resonant mode under 1.00MHz.
In one embodiment, piezoelectric cantilever sensor is by quartzy silicon and piezoelectric ceramics lead zirconate titanate (PZT) or the manufacturing of piezoelectric ceramics polymkeric substance 1-3 fibrous composite.In one embodiment, non-piezoelectric layer is by such as pottery, metal, and polymkeric substance, and such as one or more the traditional material structure of compound substance in pottery, metal and the polymkeric substance of silicon dioxide, copper, stainless steel and titanium.
The table 2 of Figure 48 illustrates the quality factor (Q) of the corresponding resonance peak of listing in the table 1 for Figure 47 of different piezoelectric cantilever sensors.Quality factor are confirmed as the ratio of resonant frequency with respect to half-peak height place peak width.Therefore, quality factor are the tolerance of resonance peak acutance.More than experiment has shown when sensor is placed on the varying environment from vacuum to the air flow environment, and the quality factor of the piezoelectric cantilever sensor that dangles are significantly reduction all.
The Q value of observing the piezoelectric cantilever sensor that dangles depends on that each the frequency mould that wherein detects the peak is usually in 10 to 70 scope.The piezoelectric cantilever sensor that this dangles, when at vacuum, air and viscosity environment, comprise when using in the fluid that its Q value descends and is no more than 20 to 35% usually.
Consider the performance of the structure of Figure 19 B-19F now.Figure 25 has shown typical resonance spectrum, and it is that the phase angle of semi-girder (aPEMCB) sensor 711 of mm size of piezoelectric excitation of the not grappling that encourages under 100mV of Figure 19 B is to the curve map of excitation frequency.First peak is the fundamental resonant mould, and it usually occurs in 200 to 300kHz frequency ranges.Second peak is second resonant mode, and it is usually located at 700kHz to 1MHz frequency range.By electrode is connected to electric impedance analyzer (Agilent HP4192A) measures the aPEMCB resonance spectrum, this electric impedance analyzer as the interface of personal computer with in interested frequency range with 100mV driving voltage continuous coverage impedance, phase angle and amplitude ratio.
Figure 26 uses the phase angle under the 100mV driving voltage curve map of excitation frequency to be shown semi-girder (fPEMCB#1) the sensor 712 aerial resonance characteristicss of mm size of piezoelectric excitation of the unmanaged flexibility of Figure 19 C.Usually, basic rank resonant mode occurs between the 200kHz to 250kHz, and the second mould frequency appears between the 800kHz to 1MHz.The quality factor of each resonance peak are listed in the table 4 of Figure 50.
Figure 27 uses the phase angle under the 100mV driving voltage curve map of excitation frequency to be shown semi-girder (abPEMCB#1) the sensor 713 aerial typical resonance spectrums of mm size of bimorph formula piezoelectric excitation of the grappling of Figure 19 D.Base rank resonant frequency occurs in 200kHz, and second mould occurs in 700kHz.The physical size and the quality factor of all sensor arrangement types are shown in table 3 and table 4 respectively.
Figure 28 has shown beam PEMCB (oPEMCB#1) the sensor 715 aerial resonance spectrums that dangle of Figure 19 E that encourages under 100mV voltage.The size of the bimorph formula of the grappling among Figure 19 B, 19C, 19D and the 19E, unmanaged flexibility, grappling and the PEMC sensor that dangles and the table 3 that resonant frequency is listed in Figure 49 respectively.Here, find out, can make the peak position of resonant frequency adapt to particular demands by changing the geometric configuration of PEMCB sensor.Therefore, piezoelectric layer 14 and non-piezoelectric layer 16 and grappling or do not anchor to the position of those layers of beam substrate 20,50, and the range of choice that the selection of the material that constitutes beam is allowed the wide resonant frequency that is used for determining that biological or chemical detects.
The table 3 of Figure 49 has shown the physical size and the aerial main mould resonant frequency of the PEMCB sensor of representing with millimeter that uses in Figure 25-28.The length of PZT and glass is respectively the size of the layer 14 and 16 among Figure 19 B-19F.Width and thickness are the sizes of each layer.The PEMCB sensor is by piezoelectric ceramics lead zirconate titanate (PZT) and quartzy silicon manufacturing.
PEMC sensor with another kind of type of the geometric configuration of semi-girder equipment at the bottom of the double-basis that is different from firm description is shown among Figure 19 G, and also manufactured and test.Use the PZT monolithic of thick 127 μ m and the quartz of thick 180 μ m to cover the unmanaged flexibility end PEMC sensor (ftPEMC) that piece (cover square) is made new geometric configuration 19.Employed PZT layer is identical with the substrate sensor platform of Figure 19 A.The cantilever free end design has 1.50 ± 0.05 * 1 ± 0.05mm 2The glassy layer of (length x width), it is bonded to 4 ± 0.05 * 1 ± 0.05mm by non-conductive adhesive 2One end of the PZT layer of (length x width).At the other end, the long PZT layer of 1.70 ± 0.05mm becomes glass tube with epoxy resin bonding (epoxied).Therefore, this cantilever free end has the exposed PZT layer of 0.8mm.Before the long PZT layer of 1.7mm is used epoxy resin bonding, use No. 30 copper cash that are welded to the BNC unitor to make top and bottom electrode thereon.The PZT layer at cantilever free end place insulate with the thick layer of polyurethane of 8 μ m.1.5 ± 0.05 * 1 ± 0.05mm 2Glassy layer be provided for the surface of the fixing and Detection of antigen of antibody.
If will discern body, be coated on the surface of PEMC or PEMCB equipment such as antibody or DNA, then any above-mentioned PEMC or PEMCB equipment can cause the formation of sensor.Under the situation of suitably coating, final sensor coating will attract and in conjunction with the analyte that is set as target, it can be airborne pathogen, airborne protein or airborne biological reagent.In one embodiment, use the PZT cantilever sensor (PEMC) of the mm size be coated with fixing BA antigen to study direct detection to airborne bacillus anthracis (BA) spore.Be detected as the variation of the PEMC equipment medium frequency that the quality by the BA that increases causes BA adhering on the PEMC sensor of coating,, so influence the mechanical resonance of cantilever equipment because the BA that adheres to influence quality.
In one embodiment, experimental provision comprises the horizontal tube that has vertically suspended PEMC sensor, and the glass surface of this sensor is towards airflow.With quartz surfaces silylation (silanylated), fixing then have the anti-BA of specific rabbit (rabbitanti-BA) to the BA pathogen, is exposed to the moving air stream (11cm/s) that every litres of air contains 42 to 278,000 spores then.Use the axial-flow type atomizer to introduce BA in the upstream of sensor.The concentration of BA solution is measured with Ku Erte grain count instrument (Coulter Counter) Multisizer II in the atomizer.This sensor is made by the PZT that is laminated to the 2 * 5mm that is anchored on the Pyrex in the non-conductive epoxy resin substrate that has the 0.5mm skew.
Figure 29 A has shown and is used to make airborne bacillus anthracis (BA) to flow to the device 100 of PEMC type sensor to detect airborne BA.The supply air 110 (A0) that is adjusted to zero humidity splits into two strands.One uses air valve 110 (A1) and is used for the BA of the concentration known of deionized water is supplied to atomizer 121.Atomizer 121 generates the about 5 microns liquid particles of size.The atomizer of low shear is used to prevent damage BA spore when the BA spore flows through atomizer.Liquid particles is carried by the auxiliary air from adjustable air valve 115 (A2), and described adjustable air valve 115 (A2) can be by 2 " regulate between Guan Zaicong about 1 to 200lpm.In the structure of Figure 29 A, two plumes mix at mixer 123 places and carry the BA of atomizing with the speed of 1m/s, but higher speed also is possible.As shown in Figure 29 B, the PEMC sensor is inserted into " T shape " in the mode of quadrature and exposes pipe assembly 125, and described sensor is connected to electric impedance analyzer 131 and collected the personal computer 135 of resonant frequency data in per 30 seconds.The humidity and the temperature of the bioaerosol that continuous monitoring is flowed.Use commercially available SASS 2000 air samplers 140 periodically discharge currents to be taken a sample, this provides 5ml fluid sample.Use the PEMC sensor in independent device, to analyze these samples or make the Ku Erte particle collector determine its particle size and distribution.SASS 2000 air samplers use the RS-232 monitoring as the interface of personal computer 150.
Flow cell 125 among Figure 11 B comprises air-flow importation 1251, air-flow main part 1252, exhausr port part 1253 and sensor mounting portion 1253.Sensor 1254 in this sensor mounting portion is positioned on the vertical direction changeably to regulate the degree of depth of passing when sensor enters airflow by main body 1252.In one embodiment, sensor be oriented to identification body with cantilever sensor be exposed to orthogonally air-flow direction so that the identification body to the exposure maximization of element in the air-flow.
Use the structure of Figure 29 A, realized the steady state frequency response of sensor at the beginning by soft air (RH=85 ± 3% and T=23 ± 0.3 degree centigrade) is flowed with the flow rate of 2.4lpm.The atomizer charge is 10,000,000 spores and atomizing 15 minutes among the 4mL, thus generate 278,000 spores of air/liter phase concentrations.The frequency of PZT cantilever is the function of the hydrodynamic character of its quality and temperature and ambient gas.When being exposed to airborne BA, because spore is attached to the cantilever equipment of coating, resonant frequency reduces 700Hz.After the detection, sensor is immersed among the PBS to discharge with the BA that will adhere to by the damping fluid that uses low pH value confirms adhering to of BA.Discharging caused frequency change by spore is 350Hz.The frequency change that causes owing to the influence of temperature and moisture is every degree centigrade of 60Hz and every centesimal relative humidity (RH) 2Hz.
The PEMC sensor depends on that structure and the mode of vibration that is used to detect can have the sensitivity of 10 femtograms.For the result of Figure 30 A, two sensors have been used.When sensor 1 is exposed to concentration is that (humidity 95% 24C) during the BA spore that flows of 278,000 spores, provides the 760Hz response to every litres of air.When using identical spore concentration, sensor 2 provides 760Hz offset response much at one.Figure 30 A also shown when using identical mould to detect, the repeatability of the excellence between the routine tests that carries out with the different sensors of like configurations.Therefore, observe success, quantitative and repeatably BA spore detection.
Figure 12 B has shown the result who exposes four sensors.Preparation has and will detect the sensor 1 (1006) and the sensor (1008) of the identification body of BA spore.Similarly, prepare to have the control sensor 1002 and 1004 of same identification body.Figure 30 B has described sensor 1 and sensor 2 in the consistance that detects result between the spore in the environment of 278,000 spores of every liter of gas.Sensor curve 1002 has been described the response of sensor to the controlled injection of the inorganic granular silicic acid alumina particles of 0.2 to 0.6 micron-scale.Sensor curve 1002 shows that the essence that do not exist as expected responds.Sensor curve 1004 has been described the response of sensor to clean air ambient.Notice that the essence that do not exist as expected responds.This detection of analytes that shows use PEMC/PEMCB sensor has high specific to employed identification body, and the sensor of constructing like this is insensitive to non-target substance.
The variation of PEMC sensor response quality, temperature and fluid density.The fluctuation of system temperature, humidity (quality and density influence) and pressure (density) can be covered the detection of pathogen.The PEMC Design of Sensor makes these cover influence and minimizes.The frequency of noting PEMC equipment responds spore propagates into time of sensor from atomizer in.The time of detecting BA is on 2 minutes level.
As mentioned above, carry out confirmation by the release in low pH damping fluid to the detection of the BA that is attached to the PEMC sensor.Also use direct microscopic examination as confirmation.In low pH damping fluid confirmed, adhering to of 2:1 was consistent to the mass change of liquid with the air of the ratio that discharges and other report.In the structure of Figure 29 A, confirm the BA atomizing by atomizer being provided thing and the air sampling equipment emission that catch (SASS 200) carry out grain size analysis.SASS 2000 has caught about 30% among the airborne BA that imports.In Figure 31, provided and detected the result who confirms.
After carrying out the experiment shown in Figure 30 A, the sensor that will be exposed to 278,000 spores of every litres of air sample inserts in the buffer release liquid (the pH value is 2.2) and measures resonant frequency.Under this pH, antigen has increased resonant frequency from the surface release of sensor and the quality that reduces, and this confirms that the reduction of frequency is because BA adheres to really.This validate result is shown in Figure 31.
Another confirmation that provides BA to adhere to by direct microexamination.The scanning electron micrograph of Figure 33 has shown the cantilever of taking apart that uses in an airborne anthrax test experience.This sensor taken apart so that can be installed on the SEM pedestal and be used for microscopic analysis then.The existence of the anthrax spores that the top figure of Figure 33 uses in being presented at and detecting in the zone of the sensor surface shown in the following figure.Photomicrograph shows that anthrax antigen is attached to the antibody of chemical fixation on sensor surface.
Note as the front and since the PEMC sensor with vibration when air-flow contact, therefore chemical bond only can take place and adhere to, thereby reduce or eliminate the caused false positive of fume by the propagation of the gas in the gas stream sample.Carry out the gas phase experiment with 0.2 to 0.6 micron clay particle as the inertia pollutant.Observe and be exposed to the variation that pollutant does not cause sensor output.This has confirmed that also the inertia pollutant is not adhered to the PEMC surface in operating process.
Therefore, be appreciated that and example shows that also sensor of the present invention can be used for the terrified reagent of detection of biological by example, detect airborne pathogen, the mark of the TNT of detection such as DNT, detect airborne toxin, and detect any other and can be incorporated into the PEMC of suitable preparation or the target analytes on PEMCB surface.Sensor of the present invention can also be implemented in sensor array, wherein with a plurality of transducer arrangements in individual equipment to detect a plurality of different analytes simultaneously.In this mode, sensor of the present invention can be used in, and for example, identifies the unknown materials in the gas, or shows whether there is multiple different analyte in the gas.
As mentioned above, detection is subjected to humidity effect.Particularly, low-down humidity influences binding affinity unfriendly.Therefore, advantageously, comprise the humidification related with airborne analyte sensor.Figure 33 has described to use the structure of the airborne sensor of Figure 29 B.In this embodiment, air pump 305 has the air intake that sucks air from air sample, such as chamber, container or chamber, and will suck pneumatic pump and deliver to humidifier 310.The air that humidifier 310 is added into pumping with a certain amount of moisture make PEMC in the flow cell 125 or PEMCB sensor with suck target analytes contained in the air and react well.PEMC/PEMCB flow cell 125 is disposed to safe position with air 315 then.Use is collected the personal computer 135 of resonant frequency data and the sensor that electric impedance analyzer 131 is measured the flow cell 125 from flow cell.Figure 33 is the PEMC/PEMCB sensor is used for the air borne detection of analyte in flow cell a simple application.
Figure 34 has described to relate to the process flow diagram of aspect of the present invention.This method relates to uses PEMC type sensor (comprising PEMC and PEMCB type) to detect airborne analyte.This method starts from providing PEMC type sensor in step 2120.These sensors can comprise any kind shown in Figure 19 A-19G and modification thereof.These types comprise the single substrate cantilever style shown in Figure 19 A and the 19G, the double-basis bottom girder sensor with non-piezoelectric beam as shown in Figure 19 B-19D, the beam type sensor with piezoelectric beam as shown in Figure 19 F and the overlapping layer structure as shown in Figure 19 E.
Next, in step 2122, the target analytes of atomizing is passed through in airflow from sensor.Here, preferably attract the identification body of analyte to be oriented air-flow orthogonally with analyte.Being exposed to airflow allows the identification body to catch target analytes.Then, in step 2124, the PEMC sensor excitation is extremely vibrated by electrode.The oscillation frequency of cantilever or beam assembly depends on the quality of assembly, and described assembly comprises the analyte of collecting by the identification body.The oscillation frequency of survey sensor in step 2126 (that is the resonant frequency of slider assembly).Then in step 2128 with the oscillation frequency of the slider assembly measured and intrinsic (resonance) bareline heart rate comparison of slider assembly.This comparison can be carried out with calculation element, and described calculation element comprises personal computer, flush bonding processor, analog or digital circuit or hand computation.
In deciding step 2130, detect frequency displacement.If as in, do not detect frequency displacement, then determine on the identification body, not have analyte in step 2132.If the airflow sample be pure or the identification body not with airflow in any analyte obtain this result when compatible.If detect frequency displacement, then in step 2134, determine to detect target analytes.Further, in step 2136, determine the concrete amount (that is, being deposited on the quality of the analyte on the identification body) of analyte.This step is undertaken by the quality association of also that this amplitude and the resonant frequency that changes the PEMC sensor is the required analyte of the amplitude of checking frequency displacement.Attention is not carried out required special preparation under the situation based on the sampling of liquid of analyte.And, to compare with detection of analytes based on liquid, said method does not comprise special concentration step or enriching step.
For quality contrast or more accurate detection of analytes are provided, between the survey sensor of control sensor and check and analysis thing, carried out comparison not shown in Figure 33.For example, control sensor is preferably identical with survey sensor, and difference is that control sensor does not have the identification body that is used for target analytes.When being exposed to the airflow identical with survey sensor, control sensor can be different from the resonant frequency of survey sensor accurate result to be provided.
Other sensor arrangement
The possessive construction of Figure 35-47 also can be used for constructing the sensor that can be used in the detection of analyte in gas or the liquid medium as the structure of Figure 19 A-19G.Therefore, the application of the structure of Figure 35-47 is used to detect airborne chemicals or biological product to discussed here similar.Has some common feature among Figure 35-47 and Figure 19 A-19G.For example, as directed, there is base members 20, it is attached to piezoelectricity 14 (P) type element or non-piezoelectricity 16 type elements.Adhesion layer 18 is separated P type layer 14 and NP type layer 16.Figure 35-47 has described to be used in point 30 each positions that are connected to piezoelectricity 14 type elements the electrode 28 of excitation cantilever arm structure or girder construction.The multiple structure that Figure 35-47 expression enough PEMC of energy and PEMCB equipment are implemented.Be the summary of each structure below.
Figure 35 has described the structure of PEMC or PEMCB sensor, wherein NP part 16 and P part 14 adjacency.Thickness (the T of NP layer 16 NP) can be along the length variations of NP layer 14, and T NPCan be designed to support sensitive sensor.In this structure, the bending modulus in NP layer 14 gap regions is less than the bending modulus of NP layer 14 than thickness portion.Though only show the free end cantilever that comprises P and NP layer, the structure of Figure 35 duplicates with can centering on center line A-A mirror image.The symmetry of beam (PEMCB) sensor has been described in the image copying of Figure 35.Described the example of several center lines among Figure 35-47, wherein describing for how much can be the sensor of free end cantilever or beam construction.In addition, all essential informations and the gap width about electrode wiring 28 and contact 30 layouts is applicable to this structure and all other structures.
Figure 36 has described two-layer NP16; One deck at the top and one deck in the bottom, if when the bending modulus of NP1 (EI) is not equal to the bending modulus of NP2, this can use effectively.Here, the mark NP1 on Figure 36 and NP2 represent that two NP layers can be different on geometric configuration and material.For example, the comparable NP2 of NP1 is little or have different shapes.And NP1 can be made and NP2 is made by pottery by glass.In Figure 35, the mirror image that centers on center line A-A can generate beam construction.In this case, distance X means that more than or equal to 0 P can or be two independent parts with mirror image anchor (anchor) adjacency.At X〉in 0 the situation, can encourage one or two P, but in one situation of back, two excitations can be synchronous.Figure 37 has described the structure similar to Figure 36, and aspect two difference.In Figure 36, NP1=NP2 is because have P1 and P2 generation axis of symmetry.Mirror image around A-A generates beam construction.In this case, X is more than or equal to zero.This means that P can or can be two independent parts with mirror image anchor adjacency.At X〉in 0 the situation, can encourage one or two P, but in one situation of back, two excitations are preferably synchronous.
Figure 38 has described to construct with like Figure 19 category-A, and difference is to have increased N16 section bar materials and parts.This structure is to realize that with respect to the advantage of Figure 19 A more controls and this structure to the resonant frequency peak position can suppress undesired mould effectively.Depend on that required performance NP116 can equal or be not equal to NP2 16.The free end cantilevered construction of Figure 38 can be converted to beam construction by simply the far-end of NP2 being fixed to base members.Also note, be designated as among Figure 38 the part of NP2 can be simply by with electrode from one section P-type material remove (laser ablation, chemical etching etc.) and use P-type material can not driver unit produce.
Figure 39 has described to construct with like Figure 19 category-A, and difference is to have increased NP1.Here, NP1 is connected to substrate 20 rather than P type layer.This structure provides improved signal, because different with the structure of Figure 19 A, thereby thereby not limited its part signal energy of the near-end of P does not dissipate and produces bigger signal.In other words, the part signal energy of Figure 19 A can lose owing to near-end is limited.The structure of Figure 39 has been represented the improvement with respect to the structure of Figure 19 A.As in the structure of Figure 35-37, can generate beam construction by adding mirror image around center line A-A.
Figure 40 has described the structure with the similar of Figure 19 F, and difference has been to increase the P and the NP zone of putting upside down and has increased P type layer 14.This structure can provide improved signal because not limited its part signal energy that makes of near-end of P does not dissipate.Therefore, produce bigger signal.Figure 41 has described similarly to construct with Figure 19 E, and difference is to have increased NP1.This structure can provide improved signal because not limited its part signal energy that makes of near-end of P does not dissipate.Therefore, produce bigger signal.Figure 42 has described similarly to construct with Figure 19 G, and the bending modulus (EI) that difference is the NP layer is as the function of length L and change.By changing this parameter, realized that the stress that concentrates on the electrode position place by increase makes sensitivity strengthen.A practical methods that realizes this as shown in Figure 43, wherein the NP layer is made of a plurality of discrete segments, the width of described a plurality of discrete segments can be empty space or the substitute material of low modulus and change along with adjacent part.Generate beam construction by in Figure 42 or 43, adding mirror image around A-A.
Figure 44 similarly constructs with Figure 36, and difference is that top NP layer has as the function of length and bending modulus (EI) that changes and the bottom that changes as length function.This be effectively Figure 43 mirror image but wherein bottom be different from top layer to generate resonant structure.In Figure 44, have only when the P layer is as shown in figure 37 sandwich construction, top layer just can be identical with bottom.Figure 45 fully concentrates on electrode points with stress to sentence the structure that generates sensitive response.And since the position of NP16 this give more stable response.Can generate girder construction by forming mirror image around the A-A center line.Because the substrate of simplifying 20 is so Figure 46 is the structure that is of value to manufacturing.Yet it provides more undesired resonant mode.Can generate girder construction by forming mirror image around the A-A center line.
Yet, should understand, though provided the details of many feature and advantage of the present invention and 26S Proteasome Structure and Function of the present invention in the description in front, but disclosed content only is illustrative, and explain therein in the scope as much as possible of the principle of the invention shown in the general wide in range implication of term of claims, in detail, especially can change on shape, size and the layout about parts.

Claims (61)

1. method that detects airborne target analytes may further comprise the steps:
The sensor of mm size is provided, and described sensor comprises:
Piezoelectric layer with first end and second end, described first end vicinity also is attached to first substrate,
Non-piezoelectric layer with first end and second end, the part of wherein said non-piezoelectric layer and described piezoelectric layer are overlapping and be attached to described piezoelectric layer,
The identification body related with described non-piezoelectric layer, the combination of wherein said piezoelectric layer, described non-piezoelectric layer and described identification body comprises bracketed part, and
Operationally be attached to the electrode of described piezoelectric layer, wherein the electro photoluminescence from described electrode makes described bracketed part vibration;
The sensor of described mm size is installed in the airflow;
The described identification body of described cantilever is exposed to described target analytes in the described airflow;
Measure the oscillation frequency of described cantilever; And
With the oscillation frequency measured and the comparison of baseline oscillation frequency to determine to be illustrated in the frequency displacement that exists of described the above target analytes of identification body.
2. method according to claim 1 wherein provides the sensor of mm size further to comprise following sensor is provided, and comprises the piezoelectric and the non-piezoelectric of linear arrangement at piezoelectric layer described in the described sensor.
3. method according to claim 1 wherein provides the sensor of mm size further to comprise following sensor is provided, and comprises two piezoelectric layers separating by adhesive at piezoelectric layer described in the described sensor.
4. method according to claim 1 wherein provides the sensor of mm size further to comprise following sensor is provided, and comprises a plurality of linear arrangement and isolated non-piezoelectric at non-piezoelectric layer described in the described sensor.
5. method according to claim 1 further comprises:
Determine the amount of the described target analytes that exists on the described identification body.
6. method according to claim 1, wherein provide the sensor of mm size further to comprise the sensor that described mm size is provided, wherein said identification body is to be selected from a kind of in the group of following composition: antibody, dna molecular, adaptive son, bacteriophage and biological chemical reagent, and wherein said selection is a kind of by in the natural and synthetic group that constitutes.
7. method according to claim 6, wherein said identification body are identification and in conjunction with the antibody of airborne analyte.
8. method according to claim 7, wherein said airborne analyte by with described antibodies chemical fixation on the cantilever sensor surface.
9. method according to claim 1, wherein the step that the described identification body of described cantilever is exposed to the described target analytes in the described airflow comprises described identification body is exposed to a kind of in the group of being made up of biological substance in the airflow and chemical substance.
10. method according to claim 9, wherein said biological substance are bacillus anthracis (Bacillus anthracis) spores.
11. method according to claim 1 further comprises:
The sensor of a plurality of mm sizes is provided in sensor array, wherein in the sensor of the described a plurality of mm sizes in the described array each all is exposed to described airflow to detect at least a analyte.
12. method according to claim 11 wherein detects described at least a analyte by measuring a plurality of frequency displacements, for the sensor of each mm size that provides a frequency displacement is arranged.
13. method according to claim 1, the step that the sensor of described mm size wherein is installed in airflow comprises installs the sensor and the described airflow of described mm size substantially orthogonally.
14. method according to claim 13, wherein said airflow is in the scope of 0.01 to 10 meter per second.
15. method according to claim 1, wherein the step that the described identification body of described cantilever is exposed to the described target analytes in the described airflow comprises and described identification body is exposed to described target analytes and need not to collect described target analytes in liquid medium.
Measure following resonant frequency 16. method according to claim 1, the oscillation frequency of wherein measuring described cantilever comprise, described cantilever vibrates at described resonant frequency after being exposed to described target analytes.
17. method according to claim 1 wherein provides the sensor of mm size to comprise the sensor that following mm size is provided, and is attached to second substrate at described second end of non-piezoelectric layer described in the sensor of described mm size.
18. a method that detects airborne target analytes may further comprise the steps:
The sensor of mm size is provided, and described sensor comprises:
The first non-piezoelectric layer with first end and second end, described first end vicinity also is attached to first substrate,
Piezoelectric layer with first end and second end, the part of wherein said piezoelectric layer is attached to the described first non-piezoelectric layer with linear arrangement,
The identification body related with the second non-piezoelectric layer, the wherein said second non-piezoelectric layer and described piezoelectric layer are overlapping and be attached to described piezoelectric layer, wherein said piezoelectric layer, the described first and second non-piezoelectric layers, and the combination of described identification body comprise bracketed part, and
Operationally be attached to the electrode of described piezoelectric layer, wherein the electro photoluminescence from described electrode makes described bracketed part vibration;
The sensor of described mm size is installed in the airflow;
The described identification body of described cantilever is exposed to described target analytes in the described airflow;
Measure the oscillation frequency of described cantilever; And
With the oscillation frequency measured and the comparison of baseline oscillation frequency to determine to be illustrated in the frequency displacement that exists of described the above target analytes of identification body.
19. a method that detects airborne target analytes may further comprise the steps:
The sensor of mm size is provided, and described sensor comprises:
Have first end that is attached to first substrate and the non-piezoelectric layer that is attached to second end of second substrate, described non-piezoelectric layer forms the beam between described first substrate and described second substrate,
Be attached to first piezoelectric layer of described non-piezoelectric layer,
With a related identification body in the group of being made up of described non-piezoelectric layer and described piezoelectric layer, the combination of wherein said piezoelectric layer, described beam and described identification body comprises bracketed part, and
Operationally be attached to the electrode of described piezoelectric layer, wherein the electro photoluminescence from described electrode makes described bracketed part vibration;
The sensor of described mm size is installed in the airflow;
The described identification body of described cantilever is exposed to described target analytes in the described airflow;
Measure the oscillation frequency of described cantilever; And
With the oscillation frequency measured and the comparison of baseline oscillation frequency to determine to be illustrated in the frequency displacement that exists of described the above target analytes of identification body.
20. method according to claim 19 wherein provides the sensor of mm size further to comprise following sensor is provided, and comprises the piezoelectric and the non-piezoelectric of linear arrangement at non-piezoelectric layer described in the described sensor.
21. method according to claim 19 further comprises:
Determine the amount of the described target analytes that on described identification body, exists.
22. method according to claim 19, wherein provide the sensor of mm size further to comprise the sensor that following mm size is provided, at the body of identification described in the sensor of described mm size for selecting a kind of by in the following group of forming: antibody, dna molecular, adaptive son, bacteriophage and biological chemical reagent, and a kind of by in the natural and synthetic group of forming of wherein said selection.
23. method according to claim 22, wherein said identification body are identification and in conjunction with the antibody of airborne analyte, and described antibody chemical fixation is on the cantilever sensor surface.
24. method according to claim 19, wherein the step that the described identification body of described cantilever is exposed to the described target analytes in the described airflow comprises described identification body is exposed to a kind of in the group of being made up of biological substance in the airflow and chemical substance.
25. method according to claim 24, wherein said biological substance are the bacillus anthracis spores.
26. method according to claim 19 further comprises:
The sensor of a plurality of mm sizes is provided in sensor array, wherein in the sensor of the described a plurality of mm sizes in the described array each all is exposed to described airflow to detect at least a analyte.
27. method according to claim 19, wherein said airflow is in the scope of 0.01 to 10 meter per second.
28. method according to claim 19, wherein the step that the described identification body of described cantilever is exposed to the described target analytes in the described airflow comprises and described identification body is exposed to described target analytes and need not to collect described target analytes in liquid medium.
Measure following resonant frequency 29. method according to claim 19, the step of wherein measuring the oscillation frequency of described cantilever comprise, described cantilever vibrates at described resonant frequency after being exposed to described target analytes.
30. method according to claim 19 wherein provides the sensor of mm size to comprise the sensor with the mm size that is positioned at second piezoelectric layer on the described beam is provided, described second piezoelectric layer and described first piezoelectric layer are separated.
31. a method that detects airborne target analytes may further comprise the steps:
The sensor of mm size is provided, and described sensor comprises:
Have first end that is attached to first substrate and the piezoelectric layer that is attached to second end of second substrate, described piezoelectric layer forms at least a portion beam between first substrate and second substrate,
Be attached to the non-piezoelectric layer of described piezoelectric layer,
With a related identification body in the group of being made up of described non-piezoelectric layer and described piezoelectric layer, the combination of wherein said piezoelectric layer, described beam and described identification body comprises bracketed part, and
Operationally be attached to the electrode of described piezoelectric layer, wherein the electro photoluminescence from described electrode makes described bracketed part vibration;
The sensor of described mm size is installed in the airflow;
The described identification body of described cantilever is exposed to described target analytes in the described airflow;
Measure the oscillation frequency of described cantilever; And
With the oscillation frequency measured and the comparison of baseline oscillation frequency to determine to be illustrated in the frequency displacement that exists of described the above target analytes of identification body; And
Determine the amount of the described target analytes that on described identification body, exists.
32. method according to claim 31 wherein provides the sensor of mm size further to comprise following sensor is provided, and comprises two piezoelectric layers separating by adhesive at piezoelectric layer described in the described sensor.
33. method according to claim 31 wherein provides the sensor of mm size further to comprise following sensor is provided, and comprises a plurality of linear arrangement and isolated non-piezoelectric at non-piezoelectric layer described in the described sensor.
34. method according to claim 31 wherein provides the sensor of mm size further to comprise the sensor that following mm size is provided, and is selected from a kind of in the group of being made up of antibody and dna molecular at the body of identification described in the sensor of mm size.
35. method according to claim 31, wherein said identification body are identification and in conjunction with the antibody of airborne analyte, and described antibody chemical fixation is on the cantilever sensor surface.
36. method according to claim 31, wherein the step that the described identification body of described cantilever is exposed to the described target analytes in the described airflow comprises described identification body is exposed to a kind of in the group of being made up of biological substance in the airflow and chemical substance.
37. a kind of in the group that method according to claim 36, wherein said biological substance are made up of bacterium, virus, egg capsule, prion and spore.
38. method according to claim 36, wherein said biological substance are the bacillus anthracis spores.
39. a device that detects airborne target analytes, described device comprises:
The sensor of mm size, described sensor comprises:
Ground floor with first end and second end, described first end vicinity also is attached to first substrate,
The second layer with first end and second end, the part of the wherein said second layer and described ground floor are overlapping and be attached to described ground floor with adhesive, and it is the material that is different from ground floor that wherein said ground floor is selected from the group and the described second layer be made up of piezoelectric and non-piezoelectric material
The identification body related with the described second layer, the combination of wherein said ground floor, the described second layer and described identification body comprises bracketed part, and
Operationally be attached to the electrode of described piezoelectric, wherein the electro photoluminescence from described electrode makes described bracketed part vibration;
The exposure pipe assembly that comprises the sensor of described mm size;
Make the atomizer of described target analytes atomizing;
To the air source of described atomizer charging, described air source also is used to make the target analytes of described atomizing to enter described exposure pipe assembly;
Collect the analyser of resonant frequency data from the sensor of described mm size, relatively determining frequency change, described frequency change is illustrated in the amount of the quality of the described target analytes of collecting on the described identification body of sensor of described mm size to wherein said analyser with the resonant frequency of the measurement of the sensor of mm size and baseline resonant frequency.
40. according to the described device of claim 39, further comprise the array of the sensor of mm size, each sensor in the described array provides frequency information to determine existing and measuring of at least a analyte to described analyser.
41. according to the described device of claim 39, wherein said analyte is the bacillus anthracis spore.
42. a method that detects airborne analyte, described method comprises:
With the surface of fixing antibody coating cantilever checkout equipment, described cantilever checkout equipment has basic rank resonant frequency;
The surface of coating is exposed to airflow,, then is attached to the surface of described coating with the airborne analyte of described fixing antibody coupling if wherein described airflow contains airborne analyte;
Measure the described resonant frequency of described cantilever checkout equipment;
Determine to be attached to the amount of the airborne analyte of described identification body.
43. a method that detects airborne analyte, described method comprises:
With the surface of identification body coating cantilever checkout equipment, described identification body has a kind of in the group of being made up of fixing antibody, adaptive son, recombinant phage and dna molecular;
The surface of coating is exposed to airflow,, then is attached to the surface of described coating with the airborne analyte of described identification body coupling if wherein described airflow contains airborne analyte;
The transducer mechanism that use is connected with calculation element determines to be attached to the amount of the airborne analyte of described identification body.
44. the device of the sensor of the airborne analyte of fixed test, described device comprises:
The gas access of input air-flow;
Main part, described main part comprise the airflow chamber that air-flow is guided to exhausr port from described gas access; And
The mounting portion of fixing described sensor, the identification body on the wherein said sensor is exposed to the described air-flow in the described main part;
Wherein said sensor is the cantilever equipment of mm size, and its detection is attached to the quality of the described analyte of described identification body.
45. according to the described device of claim 44, wherein said identification body is the antibody of fixing.
46. according to the described device of claim 44, wherein said sensor comprises cantilever equipment, a kind of in the group that described cantilever equipment is made up of free end type cantilever equipment and girder cantilever equipment, wherein said sensor comprises the layer of piezoelectric and non-piezoelectric material.
47. a device that detects target analytes, described device comprises:
Piezoelectric layer with first end and second end, described first end vicinity also is attached to first substrate;
Non-piezoelectric layer with first end and second end, the part of wherein said non-piezoelectric layer and described piezoelectric layer are overlapping and be attached to described piezoelectric layer;
The identification body related with described non-piezoelectric layer, the combination of wherein said piezoelectric layer, described non-piezoelectric layer and described identification body comprises bracketed part; And
Operationally be attached to the electrode of described piezoelectric layer, wherein the electro photoluminescence from described electrode makes described bracketed part vibration.
48. according to the described device of claim 47, wherein said piezoelectric layer further comprises the piezoelectric and the non-piezoelectric of linear arrangement.
49. according to the described device of claim 47, wherein said piezoelectric layer further comprises two piezoelectric layers separating by adhesive.
50. according to the described device of claim 47, wherein said non-piezoelectric layer further comprises a plurality of linear arrangement and isolated non-piezoelectric.
51. a device that detects target analytes, described device comprises:
The first non-piezoelectric layer with first end and second end, described first end vicinity also is attached to first substrate;
Piezoelectric layer with first end and second end, the part of wherein said piezoelectric layer is attached to the described first non-piezoelectric layer with linear arrangement;
The identification body related with the second non-piezoelectric layer, the wherein said second non-piezoelectric layer and described piezoelectric layer are overlapping and be attached to described piezoelectric layer, wherein said piezoelectric layer, the described first and second non-piezoelectric layers, and the combination of described identification body comprise bracketed part; And
Operationally be attached to the electrode of described piezoelectric layer, wherein the electro photoluminescence from described electrode makes described bracketed part vibration.
52. a device that detects target analytes, described device comprises:
Have first end that is attached to first substrate and the non-piezoelectric layer that is attached to second end of second substrate, described non-piezoelectric layer forms the beam between described first substrate and described second substrate;
Be attached to first piezoelectric layer of described non-piezoelectric layer;
With a related identification body in the group of being made up of described non-piezoelectric layer and described piezoelectric layer, the combination of wherein said piezoelectric layer, described beam and described identification body comprises bracketed part; And
Operationally be attached to the electrode of described piezoelectric layer, wherein the electro photoluminescence from described electrode makes described bracketed part vibration.
53. according to the described device of claim 52, wherein said non-piezoelectric layer comprises the piezoelectric and the non-piezoelectric of linear arrangement.
54. a device that detects target analytes, described device comprises:
Have first end that is attached to first substrate and the piezoelectric layer that is attached to second end of second substrate, described piezoelectric layer forms at least a portion beam between described first substrate and described second substrate;
Be attached to the non-piezoelectric layer of described piezoelectric layer;
With a related identification body in the group of being made up of described non-piezoelectric layer and described piezoelectric layer, the combination of wherein said piezoelectric layer, described beam and described identification body comprises bracketed part; And
Operationally be attached to the electrode of described piezoelectric layer, wherein the electro photoluminescence from described electrode makes described bracketed part vibration.
55. according to the described device of claim 54, wherein said piezoelectric layer comprises two piezoelectric layers separating by adhesive.
56. according to the described device of claim 54, wherein said non-piezoelectric layer comprises a plurality of linear arrangement and isolated non-piezoelectric.
57. a device that detects target analytes, described device comprises:
The sensor of mm size, described sensor comprises:
Substrate;
Piezoelectric layer, described piezoelectric layer arrives described substrate in its proximal attachment;
Be attached to the non-piezoelectric layer of the far-end of described piezoelectric layer;
Operationally be attached to the electrode of described piezoelectric layer, the electric excitation of wherein said electrode causes the mechanical oscillation in the described piezoelectric layer, wherein with off-resonance under the oscillating phase ratio, resonance under vibration make described sensor stand higher stress level; And
Wherein compare, to the described piezoelectric layer of the attached vicinity of the electrode of described piezoelectric layer, represent the anti-point of increased resistance in this piezoelectric layer with other point in the described piezoelectric layer.
58. according to the described device of claim 57, each stress that increases on the described piezoelectric layer of the anti-expression of wherein said increased resistance.
59. a device that detects target analytes, described device comprises:
The sensor of mm size, described sensor comprises:
Substrate;
Piezoelectric layer, described piezoelectric layer arrives described substrate in its proximal attachment;
Be attached to the non-piezoelectric layer of the far-end of described piezoelectric layer;
Operationally be attached to the electrode of described piezoelectric layer, the electric excitation of wherein said electrode causes the mechanical oscillation in the described piezoelectric layer, wherein with off-resonance under the oscillating phase ratio, resonance under vibration make described sensor stand higher stress level; And
The wherein detection of the enhancing that realizes target analytes with the stress and the electrical impedance at intensifier electrode attachment point place of the bending modulus by changing described sensor.
60. a device that detects target analytes, described device comprises:
The sensor of mm size, described sensor comprises:
Substrate;
Piezoelectric layer, described piezoelectric layer arrives described substrate in its proximal attachment;
Be attached to the non-piezoelectric layer of the far-end of described piezoelectric layer;
Operationally be attached to the electrode of described piezoelectric layer, the electric excitation of wherein said electrode causes the mechanical oscillation in the described piezoelectric layer; Wherein with off-resonance under the oscillating phase ratio, resonance under vibration make described sensor stand higher stress level; And
Wherein the geometric configuration of geometric configuration by selecting described piezoelectric layer and described non-piezoelectric layer realizes that with at least one the main high-order mode that reaches described sensor at the electrode position place detection of the enhancing of described target analytes, wherein said at least one main high-order mode are the impedance under the resonance and the function of quality factor.
61. according to the described device of claim 60, wherein:
Compare with described at least one high-order mode, the oscillator intensity of the non-bending die of described sensor descends; And
Described non-bending die does not provide perceptible contribution in the impedance of the position of described electrode under bending die resonance.
CNA2007800260308A 2006-05-10 2007-05-10 Self-exciting, self-sensing piezoelectric cantilever sensor for detection of airborne analytes directly in air Pending CN101490539A (en)

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