用于甲胎蛋白检测的表面波免疫传感器的研制

文章设计了以声表面波为振动模式的压电免疫传感器，用于检测溶液中甲胎蛋白(AFP)的含量。实验采用双通道系统进行频率变化的测定，并采用蛋白A在晶体固定AFP抗体。实验结果得到了频率变化和质量附着的定量关系，并与理论分析相比较。试验表明该免疫传感器具有较好的重复性、选择性和敏感性。     

Vapor phase detection of a narcotic using surface acoustic wave immunoassay sensors

Currently, the narcotic sniffing dog remains the most accurate, reliable, and widely used sensing technology in the war on drugs. However, recent studies done at the Institute for Biological Detection Systems at Auburn University, Auburn, AL, have shown that in the presence of extraneous odors (nontarget odors), these animals show a higher propensity for so-called false alarms. For this reason, there have been an increasing demand for a portable, highly specific vapor-sensing device capable of distinguishing a target vapor signature in a complex odor. In this paper, we present the results of a series of experiments demonstrating real-time vapor phase detection of cocaine molecules. A distinctive response or signature was observed under laboratory conditions, where the cocaine vapors were presented using an INEL vapor generator and under "field" conditions facilitated by the Georgia Bureau of Investigation Crime Lab. For these experiments, the sensor component was an ST-X quartz resonator with a center frequency of approximately 250-MHz. Anti-benzoylecgonine (anti-BZE) antibodies are attached to the electrodes on the device surface via a protein-A cross linker. We observed a large transient frequency shift accompanied by baseline shift with the anti-BZE coated sensor. After repeated experiments and the use of numerous controls, we believe that we have achieved real-time molecular recognition of cocaine molecules.     

Sensitive carbohydrate detection using surface enhanced Raman tagging

Glycomic analysis is an increasingly important field in biological and biomedical research as glycosylation is one of the most important protein post-translational modifications. We have developed a new technique to detect carbohydrates using surface enhanced Raman spectroscopy (SERS) by designing and applying a Rhodamine B derivative as the SERS tag. Using a reductive amination reaction, the Rhodamine-based tag (RT) was successfully conjugated to three model carbohydrates (glucose, lactose, and glucuronic acid). SERS detection limits obtained with a 633 nm HeNe laser were ～1 nM in concentration for all the RT-carbohydrate conjugates and ～10 fmol in total sample consumption. The dynamic range of the SERS method is about 4 orders of magnitude, spanning from 1 nM to 5 μM. Ratiometric SERS quantification using isotope-substituted SERS internal references allows comparative quantifications of carbohydrates labeled with RT and deuterium/hydrogen substituted RT tags, respectively. In addition to enhancing the SERS detection of the tagged carbohydrates, the Rhodamine tagging facilitates fluorescence and mass spectrometric detection of carbohydrates. Current fluorescence sensitivity of RT-carbohydrates is ～3 nM in concentration while the mass spectrometry (MS) sensitivity is about 1 fmol, achieved with a linear ion trap electrospray ionization (ESI)-MS instrument. Potential applications that take advantage of the high SERS, fluorescence, and MS sensitivity of this SERS tagging strategy are discussed for practical glycomic analysis where carbohydrates may be quantified with a fluorescence and SERS technique and then identified with ESI-MS techniques.     

Investigation of cocaine plumes using surface acoustic wave immunoassay sensors

Vapor sensors, aka electronic noses, are becoming an increasingly popular analytical tool for detection and identification of small molecules in the gas phase. In this paper, we present the results of a series of experiments demonstrating real-time vapor phase detection of cocaine molecules. A distinctive response or signature was observed under laboratory conditions in which the cocaine vapors were presented using an INEL vapor generator and under "field" conditions facilitated by the Georgia Bureau of Investigation (GBI) Crime Lab. For these experiments, the sensor component was a two-port resonator on ST-X quartz with a center frequency of approximately 250 MHz. On this cut of quartz, a temperature-compensated surface acoustic wave is generated via an interdigital transducer. Antibenzoylecgonine (anti-BZE) antibodies are attached to the electrodes on the device surface via a protein-A cross linker. We observed a large transient frequency shift accompanied by baseline shift with the anti-BZE coated sensor. After repeated experiments and the use of numerous controls, we believe that we have achieved real time molecular recognition of cocaine molecules.     

Modeling of surface acoustic wave strain sensors using coupling-of-modes analysis

SAW devices may be configured as strain sensors, providing passive, wireless strain measurement in demanding conditions. A key consideration is the modeling of the sensors, enabling different device designs to be considered. This paper presents a simulation scheme using coupling-of-modes (COM) analysis which allows both the frequency response of a SAW strain sensor and its bias sensitivity to be evaluated. Example applications are presented to demonstrate the use of the model.     

Emission of a surface acoustic wave by an internal acoustic wave propagating near the surface

It was observed that the propagation of an internal acoustic wave near a surface is accompanied by the excitation of a surface acoustic wave directed at an angle to the internal wave. Pis’ma Zh. Tekh. Fiz. 24, 57–61 (September 26, 1998)     

Quantitative surface acoustic wave detection based on colloidal gold nanoparticles and their bioconjugates

The immobilization scheme of monodispersed gold nanoparticles (10-nm diameter) on piezoelectric substrate surfaces using organosilane molecules as cross-linkers has been developed for lithium niobate (LiNbO3) and silicon oxide (SiO2)/gold-covered lithium tantalate (LiTaO3) of Rayleigh and guided shear horizontal- (guided SH) surface acoustic wave (SAW) sensors. In this study, comparative measurements of gold nanoparticle adsorption kinetics using high-resolution field-emission scanning electron microscopy and SAW sensors allow the frequency responses of SAW sensors to be quantitatively correlated with surface densities of adsorbed nanoparticles. Using this approach, gold nanoparticles are used as the "nanosized mass standards" to scale the mass loading in a wide dynamical range. Rayleigh-SAW and guided SH-SAW sensors are employed here to monitor the surface mass changes on the device surfaces in gas and liquid phases, respectively. The mass sensitivity ( approximately 20 Hz.cm2/ng) of Rayleigh-SAW device (fundamental oscillation frequency of 113.3 MHz in air) is more than 2 orders of magnitude higher than that of conventional 9-MHz quartz crystal microbalance sensors. Furthermore, in situ (aqueous solutions), real-time measurements of adsorption kinetics for both citrate-stabilized gold nanoparticles and DNA-gold nanoparticle conjugates are also demonstrated by guided SH-SAW (fundamental oscillation frequency of 121.3 MHz). By comparing frequency shifts between the adsorption cases of gold nanoparticles and DNA-gold nanoparticle conjugates, the average number of bound oligonucleotides per gold nanoparticle can also be determined. The high mass sensitivity ( approximately 6 Hz.cm2/ng) of guided SH-SAW sensors and successful detection of DNA-gold nanoparticle conjugates paves the way for real-time biosensing in liquids using nanoparticle-enhanced SAW devices.     

Simulation of surface acoustic wave devices

The Mason crossed-field circuit model is generalized to simulate apodized interdigital transducers without channel division. The apodized transducer model is based on the transmission line model, and the artificial transformer with different voltage and current coupling ratios is used to independently obtain the transfer function and radiation admittance. In addition, a heuristic expression for transformer current ratios is used to approximate the radiation admittance of apodized transducers. Through comparing with the multichannel model, this unichannel model is illustrated to successfully describe the frequency response of apodized interdigital transducers.     

Molecular recognition for electronic noses using surface acoustic wave immunoassay sensors

In this paper, we present the results of a series of experiments on vapor phase surface acoustic wave (SAW) sensors using a layer of antibodies as the chemically sensitive film. For these experiments, the sensor component was a ST-quartz resonator with a center frequency of approximately 250 MHz. Anti-FITC antibodies were attached to the electrodes on the device surface via a protein-A crosslinker. SAW resonator devices with various coatings were mounted in TO-8 packages, inserted into a sensor head module and subjected to various fluorescent analyte gases. Numerous controls were performed including the use of coated and uncoated devices along with devices coated with antibodies which were not specific for the target analyte. The SAW immunosensor response was monitored and a baseline frequency shift was observed when the analyte being presented was the antigen for the immobilized antibody. To provide an independent measure of antibody/antigen binding, the devices were removed from the sensor head, washed with a buffer solution to remove any unbound analyte, and then inspected using a confocal laser scanning microscope (CLSM). Since all the analytes being used in these experiments were fluorescent, this afforded us the opportunity to visualize the attachment of the analyte to the antibody film. Given the high resolution of the CLSM, we were able to identify the location of the attachment of the fluorescent analytes relative to the 1.5 /spl mu/m wide electrodes of the SAW device. We believe that these experiments demonstrate that we have achieved real time molecular recognition of these small molecules in the vapor phase.     

Chemical sensor based on surface acoustic wave resonator using Langmuir-Blodgett film

A one-port surface acoustic wave (SAW) resonators incorporating Langmuir-Blodgett (LB) films has been investigated. SAW sensors are one potential applications of SAW devices. Most of the work reported on SAW sensor concerns delay lines. In this paper we characterize the mass loading effects of one-port resonators by depositing successive monolayers of LB films onto the surface. A 90 MHz SAW gas-phase sensor has been fabricated on an ST cut quartz substrate, and one-port resonator configurations have been used as the sensing element. Ultra thin monolayers of arachidic acid and arachidic acid ethyl ester have been deposited using the LB method. The resonant frequencies and the Q values have been measured as sensor response. Experimental results show that the Q values and the resonant frequencies of the one-port SAW resonator vary with film mass loading on the SAW device surface.     

Guided shear horizontal surface acoustic wave sensors for chemical and biochemical detection in liquids.

The design and performance of guided shear horizontal surface acoustic wave (guided SH-SAW) devices on LiTaO3 substrates are investigated for high-sensitivity chemical and biochemical sensors in liquids. Despite their structural similarity to Rayleigh SAW, SH-SAWs often propagate slightly deeper within the substrate, hence preventing the implementation of high-sensitivity detectors. The device sensitivity to mass and viscoelastic loading is increased using a thin guiding layer on the device surface. Because of their relatively low shear wave velocity, various polymers including poly(methyl methacrylate) (PMMA) and cyanoethyl cellulose (cured or cross-linked) are investigated as the guiding layers to trap the acoustic energy near the sensing surface. The devices have been tested in biosensing and chemical sensing experiments. Suitable design principles for these applications are discussed with regard to wave guidance, electrical passivation of the interdigital transducers from the liquid environments, acoustic loss, and sensor signal distortion. In biosensing experiments, using near-optimal PMMA thickness of approximately 2 microm, mass sensitivity greater than 1500 Hz/(ng/mm2) is demonstrated, resulting in a minimum detection limit less than 20 pg/mm2. For chemical sensor experiments, it is found that optimal waveguide thickness must be modified to account for the chemically sensitive layer which also acts to guide the SH-SAW. A detection limit of 780 (3 x peak-to-peak noise) or 180 ppb (3 x rms noise) is estimated from the present measurements for some organic compounds in water.     

Suppression of reflection coefficients of surface acoustic wave filters using quadrature hybrids

This paper proposes a simple technique to suppress the reflection coefficients S11 and S22 of surface acoustic wave (SAW) filters. Two identical SAW filters are sandwiched in between two quadrature hybrids, where their two ports are used as input and output, and others are terminated by matched loads. First, it is shown by simulation that both [S11] and [S22] are suppressed to be less than -20 dB without deteriorating the transmission characteristics. Next, two hybrids using microstrip lines were fabricated, and two RF SAW filters for GSM850 were sandwiched in between them. The result showed that the maximum [S11] within the passband was improved from -12.5 dB to -21.7 dB, i.e., 9.2 dB suppression of [S11] was achieved by sacrificing only the insertion loss of less than 0.6 dB. We also attempted to replace the microstrip lines with lumped elements. In this case, the maximum [S11] within the passband was improved more than 7.5 dB with the increased insertion loss of less than 1.5 dB. Finally, simple discussion is given on the inclusion of the transformer function in the quadrature hybrid.     

Design of a radio-linked implantable cochlear prosthesis using surface acoustic wave devices

Cochlear prosthesis systems for postlingually deaf individuals (those who have become deaf due to disease or injury after having developed mature speech capability) are considered. These systems require the surgical implantation of an array of electrodes within the cochlea and are driven by processed sound signals from outside the body. A system that uses an analog signal approach for transcutaneous transfer of six processed speech data channels using frequency multiplexing is described. The system utilizes a filterbank of six narrowband surface acoustic wave (SAW) filters in the range 72-78 MHz with a 1.2-MHz channel spacing to multiplex the six carrier signals, frequency modulated, by the processed speech signals, onto a composite signal. The same SAW filters are used in the receiver filterbank for signal separation, but are housed in a miniaturized package. The system includes a portable transmitter and a receiver package which is to be implanted in the patient. The implanted circuits are supplied exclusively from power transferred from outside the body via a separate 10-MHz transcutaneous link.     

Analysis of liquid-phase chemical detection using guided shear horizontal-surface acoustic wave sensors

Direct chemical sensing in liquid environments using polymer-guided shear horizontal surface acoustic wave sensor platforms on 36 degrees rotated Y-cut LiTaO3 is investigated. Design considerations for optimizing these devices for liquid-phase detection are systematically explored. Two different sensor geometries are experimentally and theoretically analyzed. Dual delay line devices are used with a reference line coated with poly (methyl methacrylate) (PMMA) and a sensing line coated with a chemically sensitive polymer, which acts as both a guiding layer and a sensing layer or with a PMMA waveguide and a chemically sensitive polymer. Results show the three-layer model provides higher sensitivity than the four-layer model. Contributions from mass loading and coating viscoelasticity changes to the sensor response are evaluated, taking into account the added mass, swelling, and plasticization. Chemically sensitive polymers are investigated in the detection of low concentrations (1-60 ppm) of toluene, ethylbenzene, and xylenes in water. A low-ppb level detection limit is estimated from the present experimental measurements. Sensor properties are investigated by varying the sensor geometries, coating thickness combinations, coating properties, and curing temperature for operation in liquid environments. Partition coefficients for polymer-aqueous analyte pairs are used to explain the observed trend in sensitivity for the polymers PMMA, poly(isobutylene), poly(epichlorohydrin), and poly(ethyl acrylate) used in this work.     

Full-circular surface acoustic wave excitation for high resolution acoustic microscopy using spherical lens and time gate technology

With a fixed gate width under the condition where the focus of an acoustic lens was set inside the sample, we varied signal taking-in time. Discrimination was made between differences in time required for an ultrasonic signal reflected from the sample to reach the acoustic lens. This process also enabled three types of images to be obtained separately: the surface reflection wave image, a combination of images based on the interference of the surface reflection wave with surface acoustic waves, and the surface acoustic wave image. Thus it was presumed that this process also would reveal the causes of image contrast and allow an easy interpretation of images. Furthermore, the image resolution was improved, because the surface acoustic wave image was drawn by an ultrasonic beam produced by full-circular surface acoustic wave excitation propagating toward the center converging concentrically; the theoretical resolution was 0.4 times the value of the surface acoustic wave wavelength lambda(R) and independent of the defocus value of the acoustic lens. Several kinds of samples were observed with this method. The results showed that the new method permitted observation of the internal structures of samples while offering new knowledge through the data reflecting the ultrasonic wave damping and scatter drawn on the display.     

Response to cardiac markers in human serum analyzed by guided-mode resonance biosensor

Cardiac markers in human serum with concentrations less than 0.1 ng/mL were analyzed by use of a guided-mode resonance (GMR) biosensor. Cardiac troponin I (cTnI), creatine kinase MB (CK-MB), and myoglobin (MYO) were monitored in the serum of both patients and healthy controls. Dose-response curves ranging from 0.05 to 10 ng/mL for cTnI, from 0.1 to 10 ng/mL for CK-MB, and from 0.03 to 1.7 μg/mL for MYO were obtained. The limits of detection (LOD) for cTnI, CK-MB, and MYO were less than 0.05, 0.1, and 35 ng/mL, respectively. Analysis time was 30 min, which is short enough to meet clinical requirements. Antibody immobilization and the hydrophilic properties of the guided-mode resonance filter (GMRF) surface were investigated by X-ray photoelectron spectroscopy (XPS) and by monitoring the peak wavelength shift and water contact angle (CA). Both assays used to evaluate the surface density of the immobilized antibodies, a sandwich enzyme-linked immunosorbent assay (ELISA) and a sandwich immunogold assay, showed that the antibodies were successfully immobilized and sufficiently aligned to detect the low concentration of biomarkers. Our results show that the GMR biosensor will be very useful in developing low-cost portable biosensors that can screen for cardiac diseases.     

Low-loss and wide-band double-mode surface acoustic wave filters using pitch-modulated interdigital transducers and reflectors

This paper proposes use of pitch-modulated interdigital transducers (IDTs) and reflectors for the realization of low-loss and wideband longitudinally coupled double-mode surface acoustic wave (DMS) filters. This technique offers drastic improvement of the device performances through the introduction of a sufficient number of degrees of freedom in the DMS filter design. Namely, the pass-band becomes wide and flat, and insertion loss can be reduced through the suppression of the bulk acoustic wave (BAW) scattering. First, it is shown how the BAW scattering loss can be reduced by the use of the pitch-modulated structure. The DMS filter with this structure is designed so that the frequency response becomes similar to that of the filter with the conventional unmodulated structure, and device performances are compared both theoretically and experimentally. It then is demonstrated how the total device performances are improved by the use of this technology when the device is designed optimally for given specifications. Adding to the reduced bulk wave scattering loss, various distinctive features offer drastic improvement of total device performances.     

A surface acoustic wave biosensor concept with low flow cell volumes for label-free detection

Special surface acoustic wave (SAW) devices using horizontally polarized surface shear waves can be operated in water. They allow an easy detection of molecules with biological relevance (e.g., proteins) via direct detection of the adsorbed mass. The transducer structures of conventional SAW devices are usually connected to the electronics by bond wires. In consequence, flow cell volumes can hardly be designed smaller than 50 microL. A new type of SAW device that is coupled capacitively with the electronics enables the reduction of flow cell volumes down to 60 nL, which decreases sample consumption and reduces the length of the measurement cycles down to a few minutes. To create an immunosensor, the SAW devices first are coated with a thin parylene layer for creating a sensor surface that is chemically homogeneous. Then OptoDex, a dextran containing both photoactive and functional groups is immobilized photochemically. Finally, antibodies are coupled via conventional EDC/NHS chemistry. The technique has been used to monitor urease binding at anti-urease-coated SAW devices in real time and with good resolution. Because of the simple sensor handling and the economical sample use, the new SAW device is particularly suitable for the design of an array.     

Surface acoustic wave measurements of surface cracks in ceramics

An investigation of scattering from surface cracks has been conducted. In particular, the change in the reflection coefficient of a Rayleigh wave incident on a surface indentation crack has been measured as the sample is stressed to fracture. The acoustic measurements have been correlated with the stable crack extension that precedes final failure. The crack extension behavior of as-indented specimens was found to differ appreciably from that of annealed specimens. Cracks in the annealed samples exhibited partial crack tip closure, but little stable extension, whereas cracks in the as-indented samples displayed both crack closure and irreversible crack growth. This behavior has been rationalized by invoking concepts based upon the residual stresses created by indentation.