Thickness-shear Mode Acoustic Wave Sensor Research Articles

Label-free methods for probing the interaction of clioquinol with amyloid-β

The presence of amyloid-β (Aβ) fibrils is characteristic of Alzheimer's disease (AD), and the aggregation of these amyloidogenic proteins is a nucleation-dependent process. In this report, label-free methods based on surface plasmon resonance (SPR) and thickness shear mode acoustic wave sensors (TSM-AWS) were used to detect monomer elongation in real-time. The modulation of Aβ aggregation using a well-described flavonoid, clioquinol (CQ) was also observed. Established methods like fluorescence and electrochemistry were also employed to confirm the interaction of CQ with Aβ. Good correlation between the designed label-free methods creates a promising platform for the screening of novel amyloid inhibitors.

Thickness-shear vibration of an elastic plate carrying an array of rigid microbeams with consideration of couple stresses

We study thickness-shear vibration of an elastic plate carrying an array of rigid microbeams with their bottoms attached to the top surface of the plate. The beams undergo rigid-body translation and rotation when the plate is in thickness-shear motion. The plate is modeled by the couple-stress theory of elasticity to properly take into account both the shear forces and the bending moments at the bottoms of the beams. A equation that determines the resonant frequencies of the structure is derived. Analytical and numerical examinations of a few special cases of the general frequency equation reveal a few basic effects of the microbeams and the couple stress. The results are useful in measuring geometric/physical properties of the microbeams using plate thickness-shear mode acoustic wave sensors.

Interaction of cationic surfactants with DNA detected by spectroscopic and acoustic wave techniques

Interaction of the cationic surfactants benzalkonium chloride and 1-hexadecylpyridinium chloride, in the concentration range 0.1 microM to 1 mM with calf thymus DNA and with short 19-mer double-stranded DNA has been examined in solution using UV absorption and fluorescent spectroscopies and at the liquid-solution interface by thickness-shear mode acoustic wave sensor. Higher concentrations of surfactant resulted in an increase of UV absorption, and decrease of melting temperature and van't Hoff enthalpy of calf thymus DNA. Both surfactants induce fluorescence quenching of ethidium bromide which is also associated with intercalation of the molecules into the nucleic acid strand. The effect of the pyridinium compound is greater than for the other surfactant likely because of the lower size of polar head group in this molecule. With respect to acoustic wave detection at the device surface, for relatively low surfactant concentrations (below 100 microM), decreases of both series resonant frequency and motional resistance were observed. At higher surfactant concentration both parameters increased. These effects are attributed to acoustic coupling processes that occur at the device-film/liquid boundary.

Depolarization of surface-attached hypothalamic mouse neurons studied by acoustic wave (thickness shear mode) detector

Isolation of neurons from animal tissue is an important aspect of understanding basic biochemical processes such as the action of hormones and neurotransmitters. In the present work, the focus is on an effort to evaluate the utility of acoustic wave physics for the study of such cells. Immortalised hypothalamic neuronal cells from mouse embryos were cultured on the surface of the gold electrode of a 9.0 MHz thickness-shear mode acoustic wave sensor. These cells, which are clonal, are imposed on the surface of the device at a confluence in the range of 80-100%. The coated sensor is incorporated into a flow-injection configuration such that electrolytes can be introduced in order to examine their effects through measurement by network analysis. Both series resonance frequency, fs, and motional resistance, R(m), were measured in a number of experiments involving the injection of KCl and NaCl into the sensor-neuron system. The various responses to these electrolytes were interpreted in terms of changes in cellular structure associated with the depolarization process. The sensor-neuron system was found to elicit different responses to the addition of KCl and NaCl. Preliminary findings indicate that the TSM sensor does not purely measure changes in the membrane potential upon KCl addition. Typical changes in fs for 15 mM, 30 mM and 60 mM KCl additions were 54 +/- 15, 80 +/- 26 and 142 +/- 58 Hz (mean +/- standard deviation) respectively. Typical changes in R(m) for these KCl additions were 7 +/- 3, 13 +/- 4 and 23 +/- 6 Omega, respectively. These results were concluded after 17 runs at each concentration. Despite the large relative standard deviations, the dependence of f(s) and R(m) with respect to concentration was apparent. Controls performed by coating the TSM sensor with laminin or a cell attachment matrix showed no significant changes in either f(s) or R(m) for the same solutions tested on the sensor-neuron system.

Experimentally fitting the attraction strength of an interface by the response of the thickness shear-mode acoustic wave sensor

The thickness shear-mode (TSM) sensor is extended for operating in a liquid environment for application in biological engineering. The interfacial effect between the sensor surface and the attached medium is one of the major controversies in modelling of the TSM resonator in a liquid environment. Several slip models have been proposed to describe the interfacial mechanism of a TSM resonator in a liquid environment. In this paper, the correlation between the spring–damper model and other slip models is presented. Three TSM sensors with different surface modifications were fabricated to verify the models. The results of the measured experimental frequency shifts are found to deviate from theoretical results evaluated using a non-slip model. By adjusting the attraction strength between the contacted interfaces, the results can be fitted by the spring–damping interface model.

Acoustic coupling at multiple interfaces and the liquid phase response of the thickness shear-mode acoustic wave sensor

Interfacial slip at two interfaces is included in an acoustic wave model for a transverse-shear mode (TSM) device, coated with a thin viscoelastic film in contact with a liquid, producing series resonant frequency (fs) and motional resistance (Rm) shifts in the same direction.

An acoustic wave biosensor for human low-density lipoprotein particles: construction of selective coatings

Cholesterol is found in four major classes of blood particles including chylomicrons, very low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). The most studied fraction is LDL as it is most closely associated with heart disease. The challenge in current methods of analysis is the determination of the cholesterol in the individual lipoprotein fractions. Accordingly, the critical step in any analysis is the complete separation of the lipoprotein fractions. In this work, enhanced selectivity for the LDL fraction was achieved by the covalent binding of dextran sulfate (DS) to the gold surface of a thickness shear-mode acoustic wave sensor. The thickness and surface concentration of the DS layer was estimated by in situ ellipsometry to be 219 Å and 0.8 ng/mm 2, respectively, but it was difficult to construct the sensing layer reproducibly. The DS coated sensor was ten times more responsive to LDL than the other lipoprotein (LP) fractions. The sensor was a main component in a flow injection analysis system that exposed LDL, VLDL and HDL to not only the DS layer, but also to the underlayers used in the construction of the DS layer. A possible regeneration solution was found which would rinse the LDL from the layer, restoring the sensor for repeated use. Frequency shifts from LP absorption into the DS layer were corrected for dissipative losses through the DS layer using an oscillator circuit equipped with an automatic gain control feature.

Nanoscale investigation on nature of dark hole in moisture-exposed tris(8-hydroxyquinoline) aluminum thin films

The morphological evolution and nature of the degradation of the moisture-exposed tris(8-hydroxyquinoline) aluminum (Alq 3) thin films have been microscopically investigated by variable-temperature tapping mode atomic force microscopy and complementarily by thickness-shear mode acoustic wave sensor. It is plausibly ascertained that the dark hole in the Alq 3 films results from the release of the volatile 8-hydroxyquinoline, a product of the reaction of Alq 3 with moisture.

An acoustic wave sensor incorporated with a microfluidic chip for analyzing muscle cell contraction.

We report the fabrication of a microfluidic chip or lab-on-a-chip integrated with a thickness-shear mode (TSM) acoustic wave sensor for muscle cell analysis. The sensor, essentially an AT-cut quartz crystal, serves as a detector for recording changes in acoustic wave properties occurring in an attached cardiomyocyte (single heart muscle cell) during its contraction and relaxation. Presumably, the changes resulted from alterations in viscoelastic properties (e.g. stiffness) of the cells. The effects of excitation electrode size, the presence of a microfluidic channel plate, and liquid loading on the sensor were first examined. Thereafter, muscle cell contraction analysis upon chemical stimuli were described. The potential of the chip for screening of cardiovascular drugs is discussed.

Electrode modification and the response of the acoustic shear wave device operating in liquids

The effect of electrode polarity, geometry, and stray capacitance on the performance of the thickness-shear mode acoustic wave sensor operating in electrolytes and solutions of biomolecules has been studied. In contrast to the well-known mass-based response of the device operating in the gas phase, the response in a liquid is governed by several factors including acoustoelectric and fringing field effects, which are known to be active at the edges of the electrodes. In order to investigate and utilize these effects, we modified the electrode geometry to increase the edge length, which, in turn, raises the sensitivity of the device. These changes which constituted either complete coverage of the back of the device with electrode material, or the removal of disks and lines from the electrode surface, resulted in a two to three times enhancement of sensor response. Such modifications that extend device sensitivity beyond the electrode area to the quartz region of the sensing structure also provide a better surface for the immobilization of various probes. We verified the enhancing ability of the modified electrodes for the case of adsorption of the protein avidin and neutravidin, followed by their affinity reactions with biotinylated biomolecules. It was found that the active electrode in contact with electrolyte exhibits a sensitivity of about twice that of the grounded electrode. The existence of stray capacitance around the cell was confirmed by shielding the cell assembly with a bath of concentrated KCl solution. This shielding effect was measured to be about 25-60 Hz in series resonant frequency and -1000 Hz in parallel resonant frequency.

Adsorptions of plasma proteins and their elutabilities from a polysiloxane surface studied by an on-line acoustic wave sensor.

Gold electrodes of thickness-shear mode acoustic wave sensors were modified with poly[(mercaptopropyl)methylsiloxane]. The flow-through adsorption of three major plasma proteins (human serum albumin, fibrinogen, and immunoglobulin G) was detected by acoustic network analysis. The elution of fibrinogen and albumin from coated and unmodified gold surfaces by sodium dodecyl sulfate was studied with respect to different adsorption times and protein concentrations. Both sequential and competitive adsorptions of the three proteins on polymer-modified surfaces of sensors were examined as were simultaneous adsorptions from binary and ternary mixtures. The experimental results confirm that the competitive behaviors of proteins in terms of adsorptive processes are explained by factors other than displacement phenomena.

Surface energy and the response of transverse acoustic wave devices in liquids

A magnetic acoustic resonator sensor was silanized with octadecyltrichlorosilane in order to produce a hydrophobic surface. Confirmation of the presence of the silane film was obtained from quantitative X-ray photoelectron spectroscopy and from measurement of advancing water contact angle. Frequency shifts for operation of the device in water, compared with air, were much smaller than for bare, untreated sensors. This result is consistent with analogous experiments conducted with the thickness-shear mode acoustic wave sensor. Atomic force microscopy showed that the cavities (depth, 2.9 nm; width, 11 nm) present on the bare surface numbered about 2860 per square micrometer. The calculated frequency shift associated with cavity-trapped water for the hydrophilic sensor was about half the value found by experimental measurement, assuming all similar-sized cavities on the hydrophobic device are filled with gas. Furthermore, since the cavities on the latter surface were largely filled by silane the level of supposed trapped gas was much reduced, leading to a gross overestimate of the possible air to water shift in frequency. The results of this work confirm that an alternative explanation for surface free energy effects connected to acoustic device responses is required.

Signal Enhancement using A Swellable Polymer TSM Acoustic Wave Sensor Coating

ABSTRACT The generation of large changes in the crystal frequency is a highly sought-after goal in designing a successful thickness-shear mode (TSM) acoustic wave sensor application. We examined the potential for modulating the mass loading and viscoelastic properties of a swellable polymeric coating to achieve this goal. Using a 10 MHz AT-cut crystal with an immobilized coating of a styrene-divinylbenzene copolymer, a high molecular weight target analyte with complementary ionic and molecular binding properties was selected. Injection of the antibiotic cefoperazone in a sodium acetate buffer generated exceptionally large changes in frequency, in the range 500 - 5000 Hz. The rate of change in frequency is proportional to the analytical concentration. A multi-step regeneration protocol allows the coating to be reused multiple times. These results suggest that TSM sensor sensitivities can be significantly enhanced for selected analytes by the judicious selection of an appropriate swellable polymer coating.

Organic vapor detection using quartz crystal sensors coated by sputtering of porous sintered-polymer targets

A lipophilic hydrocarbon–polymeric film applicable to hydrocarbon gas sensing at the ppm level was prepared by radiofrequency sputtering of a porous sintered-polyethylene (PE) disk on to an AT-cut quartz crystal resonator as a mass transducer. The hydrocarbon polymeric structure was confirmed by hydrogen forward scattering–Rutherford backscattering spectroscopy and X-ray photoelectron spectroscopy. This thickness-shear mode acoustic wave sensor was also sensitive to polar organic vapors owing to the incorporation of 8% of oxygen. Fluoropolymer films without oxygen can also be produced by rf sputtering of a porous sintered-poly(vinylidene fluoride) (PVDF) disk. The sorption behaviors of the PE and PVDF films for 20 ppm primary alcohols showed proportional and inversely proportional relationships, respectively, with the polarizabilities of solute molecules. Although 100 ppm toluene vapor did not induce mechanical damping of the PE film owing to its swelling or softening, its sorption capacity strongly decreased during iterative sorption tests. However, 100 ppm ethanol vapor did not cause such an abrupt decrease in sorption capacity over 10-cycle iterative tests.

Protein adsorption to organosiloxane surfaces studied by acoustic wave sensor.

Surfaces of the two organosiloxanes, polymercaptopropylmethylsiloxane and octaphenylcyclotetrasiloxane, were prepared on the gold electrodes of thickness-shear mode acoustic wave sensors. Compounds containing the siloxane bond are important in the fabrication of medical implants. The flow-through adsorption of the proteins: human serum albumin, alpha-chymotripsinogen A, cytochrome c, fibrinogen, hemoglobin, immunoglobulin G and apo-transferrin to the two siloxane surfaces and a gold electrode were detected by acoustic network analysis. With the exception of minor wash-off by buffer flow, the adsorption of all proteins to the three surfaces is irreversible. Differences observed for the magnitudes of adsorption for the various cases are ascribed to the role played by molecular interactions at the liquid/solid interface. The results confirm that changes in series resonant frequencies caused by macromolecular adsorption differ significantly from the widely accepted "mass based" model usually employed to characterize the response of this type of acoustic wave device.

Adhesion of human platelets to collagen detected by 51Cr labelling and acoustic wave sensor

Selective adhesion of human platelets to layers of collagen Type I, immobilized on silicon wafers, has been confirmed using 51Cr radiolabelling of platelets. Corresponding experiments conducted with collagen-treated thickness-shear mode acoustic wave sensors resulted in changes in series resonant frequency in the range 35–43 Hz. Control experiments with sensors, coated with bovine serum albumin, displayed significantly reduced response. Similar reduced values were also obtained when EDTA was present and Mg 2+ was absent from the assay-buffer solution. Direct correlation of the sensor results with 51Cr labelling experiments confirms that the conventional quartz crystal microbalance description is completely inadequate to explain the magnitude of the sensor response, which is 200 times less than that predicted by the well-known Sauerbrey expression.

Kinetics of hybridization of interfacial RNA homopolymer studied by thickness-shear mode acoustic wave sensor

The impedance response of RNA homopolymer hybridization on the electrode-solution interface of thickness shear mode acoustic wave sensors has been examined on a real-time basis by network analysis. The effects of blocking agents conventionally used to avoid nonspecific adsorption, solution ionic strength and temperature on the rate of interfacial hybridization have been examined quantitatively in terms of a pseudo-first order effective rate constant. A hybridization mechanism involving transport of RNA probe molecules in solution followed by duplex formation is proposed. The results suggest that the use of blocking agents is not necessary and that the biosensor is capable of the direct detection of hybridization in the present of nonspecific adsorption.

Characterization of polymer films of pyrrole derivatives for chemical sensing by cyclic voltammetry, X-ray photoelectron spectroscopy and vapour sorption studies.

Eight different conducting polymer films formed from pyrrole and N-substituted pyrrole derivatives were characterized by cyclic voltammetry, X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy. In particular, the XPS of poly[N-butylpyrrole], poly[N-(2-carboxyethyl)pyrrole], poly[N-(6-hydroxyhexyl)pyrrole] and poly[N-(6-tetrahydropyranylhexyl)pyrrole] is reported for the first time. The vapour sorption properties of these films were also examined by forming the films onto the electrodes of thickness-shear mode acoustic wave sensors. The influence of the pendant side chain is apparent in both the electrochemical behaviour, composition, doping level, morphology and the nature and extent of polymer-vapour interactions. The latter can be rationalized by consideration of vapour physical properties and solvatochromic parameters.

Effect of redox state on the response of poly-N-(2-cyanoethyl)pyrrole coated thickness-shear mode acoustic wave sensors to organic vapours

Different redox states of poly-N-(2-cyanoethyl)pyrrole (PCPY) films were prepared by electropolymerization and subsequent oxidation or reduction on the surface of thickness-shear mode (TSM) acoustic wave sensors. The resulting films were characterized by cyclic voltammetry, impedance spectroscopy, X-ray photoelectron spectroscopy and scanning electron microscopy. The response of the coated sensors to organic vapours consisting of 9-carbon chains with different functionalities was also studied. The observed responses were dependent on both film redox state and organic vapour properties. All films showed high sensitivity to nona-3,6-dien-1-ol, an aroma component characteristic of early degradation of fresh fish. Principal components analysis allowed all five analytes to be distinguished in the discriminant plane using only different redox state PCPY films.

Selective detection of aroma components by acoustic wave sensors coated with conducting polymer films

Eight conducting polymer films of polypyrrole and its derivatives were used as sensitive and selective coatings for thickness-shear mode (TSM) acoustic wave sensors. They were applied to the detection of volatile alcohols and carbonyl compounds, which are important fish freshness determinants. The conducting polymers were synthesized and coated on TSM devices by electrochemical oxidation. The exposure of the coated TSM sensors to four compounds (pent-1-en-3-ol, oct-1-en-3-ol, nona-3,6-dien-1-ol and nona-2,6-dienal) was investigated, and a linear response with concentration found for the different aroma components. The sensor response was also found to be proportional to the film thickness. The response patterns obtained by grouping the data from the individual sensors are characteristic for each aroma molecule, and were investigated using both cluster and principal components analysis. The results demonstrate the feasibility of fish freshness determination through the use of a TSM sensor array combined with pattern recognition techniques.