Coupling Medium Research Articles

An investigation of the role of cavitation in low-frequency ultrasound-mediated transdermal drug transport.

Low-frequency ultrasound (20 kHz) has been shown to increase the skin permeability to drugs, a phenomenon referred to as low-frequency sonophoresis (LFS). Many previous studies of sonophoresis have proposed that ultrasound-induced cavitation plays the central role in enhancing transdermal drug transport. In this study, we sought to definitively test the role of cavitation during LFS, as well as to identify the critical type(s) and site(s) of cavitation that are responsible for skin permeabilization during LFS. Pig full-thickness skin was treated by 20 kHz ultrasound and the effect of LFS on the skin permeability was monitored by measuring the increase in the skin electrical conductance. A high pressure LFS cell was constructed to completely suppress cavitation during LFS. An acoustic method, as well as chemical and physical dosimetry techniques, was utilized to monitor the cavitation activities during LFS. The study using the high-pressure LFS cell showed definitively that ultrasound-induced cavitation is the key mechanism via which LFS permeabilizes the skin. By selectively suppressing cavitation outside the skin using a high-viscosity coupling medium, we further demonstrated that cavitation occurring outside the skin is responsible for the skin permeabilization effect, while internal cavitation (cavitation inside the skin) was not detected using the acoustic measurement method under the ultrasound conditions examined. Acoustic measurement of the two types of cavitation activities (transient vs. stable) indicates that transient cavitation plays the major role in LFS-induced skin permeabilization. Through quantification of the transient cavitation activity at two specific locations of the LFS system, including comparing the dependence of these cavitation activities on ultrasound intensity with that of the skin permeabilization effect, we demonstrated that transient cavitation occurring on, or in the vicinity of, the skin membrane is the central mechanism that is responsible for the observed enhancement of skin permeability by LFS. LFS-induced skin permeabilization results primarily from the direct mechanical impact of gas bubbles collapsing on the skin surface (resulting in microjets and shock waves).

Dry-coupled Pulse Echo Ultrasonic Inspection Methodology for Solid Graphite Products of Rocket Boosters

High modulus solid graphite products are used in nozzle throats of solid rocket boosters. Functionally, nozzle throats are critical and hence require to be inspected thoroughly. Ultrasonic method can be utilised for detecting tight defects/cracks and estimating material properties, such as elastic modulus, grain size, uniformity of structure, etc. For ultrasonic energy to pass to the material, a liquid coupling medium is used conventionally, and hence, commercially available transducers are meant for usage with a liquid couplant. Such a liquid couplant is harmful to graphite products and hence cannot be used. Replaceable solid couplant transducer faces have been developed that can be used on conventional probes for inspection of any product. Studies were conducted to understand various aspects of ultrasonic inspection for critical applications. This paper details the experimentation conducted and analysis done on signals collected for evolving an application methodology and a procedure.

Development of a new ultrasonic technique for bone and biomaterials in vitro characterization.

Classical techniques based on bone imaging allow visual examination or provide quantitative parameters like bone mineral density, which is a mass per unit of surface. Unfortunately, these techniques are generally expensive. A new method of bone characterization that uses ultrasound techniques is presented in this article. This method is able to evaluate mechanical properties like Young's modulus E and cortical bone thickness with low-frequency transducers and does not require the use of a coupling medium. Some results of Young's modulus measurements are presented and compared to the literature values and the pulse echo method.

Efficacy of lignocaine gel for outpatient laser treatment in inflamed eyes.

To evaluate the efficacy and safety of topical 2% lignocaine gel in providing analgesia during outpatient transpupillary or trans-scleral laser treatment of inflamed eyes. A prospective study was carried out of consecutive eligible eyes undergoing laser treatment using 2% lignocaine gel as a topical anaesthetic and a coupling medium. At the conclusion of each procedure, patients were asked to grade a pain score (0 = no discomfort, 1 = mild discomfort, 2 = mild pain, 3 = moderate pain, 4 = severe pain). Twenty eyes in 19 patients received laser treatment. No pain was reported in 95% of cases treated (no discomfort in 75%, mild discomfort in 20%) and only mild pain in 5% (one patient). No adverse reactions were encountered in any of the patients. There were no complications associated with the procedures. Lignocaine 2% gel is safe and effective for outpatient transpupillary and trans-scleral laser treatment in inflamed eyes, providing adequate analgesia and serving as a coupling medium at the same time.

Clinical, histologic, and electron microscopy study of skin exposed to low-frequency ultrasound.

The use of low-frequency ultrasound has been proposed to enhance the transdermal transport of various drugs, a technique referred to as sonophoresis. The aim of the present study was to determine the safety of low-frequency sonophoresis on human and rat skin by evaluating their structural modifications after ultrasound exposure. Human skin samples and hairless rats were exposed to 20 kHz ultrasound in vitro and in vivo, respectively. Ultrasound was used with average intensities ranging from 0.25 to 7 W/cm(2) in pulsed or continuous mode. Hairless rats were also exposed to a heat source mimicking the temperature versus time profile during sonication. Skin samples were observed under optical and electron microscopy to detect any structural changes. Human skin samples exposed to intensities lower than 2.5 W/cm(2) showed no modification. For hairless rats, slight and transient erythema was observed after 2.5 W/cm(2) exposure, whereas deep lesions (dermal and muscle necrosis) were observed 24 hr later. These lesions were also observed when a plastic film was placed between the coupling medium and the animals' skin during sonication. In contrast, no histologic lesion could be seen when a heat source was applied to animal skin. Low-frequency ultrasound induces delayed and deep lesions in hairless rat skin at 2.5 W/cm(2) which are not only attributable to the increase in temperature at the skin surface during ultrasound exposure. By using the same ultrasound conditions, human skin seems to be less sensitive in vitro.

A new transducer holder mechanism for pipe inspection

A new transducer holder mechanism has been designed and fabricated for pipe inspection by cylindrical guided waves. Commercially available ultrasonic transducers have been used to generate compressional ultrasonic waves in the coupling medium. Those waves are converted to cylindrical guided waves in the pipe by the new coupling mechanism. A number of advanced coupling mechanisms developed recently for large plate and pipe inspection require the presence of a coupling fluid between the ultrasonic transducer and the pipe or plate specimen. These mechanisms can be used for inspecting horizontal pipes and plates. The new coupling mechanism presented in this article uses solid material as the coupler and can be used equally well for inspecting horizontal as well as inclined or vertical pipes. The new coupling mechanism has been designed to generate efficiently different Lamb modes in the pipe. The new design has been used to inspect different kinds of anomalies in copper and aluminum pipes. The preliminary results show that a number of Lamb modes, when generated properly by the new coupling mechanism, are very sensitive to the pipe defects. These experimental results along with the new design of the coupling mechanism are presented in this article.

Quality control of laser welds of tailored blanks using guided waves and EMATs

In modern design of automobile bodies reduction in weight and maximisation of the structural stiffness and passive safety are the main challenge. The ‘tailored blank’ has contributed to achieving a significant weight reduction in recent years. Single flat sheets are joined by laser welding into the desired configuration without filler wire. Usually the quality of the welds is assured by precise preparation of the plate edges and measurement of two of the process parameters. However, due to process deviations, defects occur, which make non-destructive testing (NDT) necessary. These defects include incomplete welding, lack of fusion, misalignment of the weld, holes and porosity. The paper presents a versatile ultrasonic (UT) inspection technique designed for in-line inspection of laser welds of tailored blanks. Conventional ultrasonic tetsing is ruled out because of the necessary liquid coupling medium. Therefore, the proposed inspection approach is based on the application of guided ultrasonic (plate) waves with shear horizontal polarisation excited and detected by couplant-free electromagnetic acoustic transducers (EMATs).

Nondestructive inspection of delamination in IC packages by high-frequency microwaves

Delamination in IC packages was detected by microwaves. An open-ended coaxial line sensor was employed to couple microwave signals with the package and the package was scanned in two perpendicular directions on a plane parallel to the package. A microwave image was created by measuring the phase of the effective reflection coefficient at the aperture of the coaxial line sensor. A high-frequency microwave was used to obtain a higher spatial resolution. The image obtained from the microwave measurement shows almost the same features as that of a scanning acoustic tomograph. The delamination was detected significantly without a coupling medium. This indicates that microwave imaging is a promising technique for the integrity assessment of IC packages.

NDI of delamination in IC packages using millimeter-waves

To detect delamination in integrated circuit (IC) packages, a millimeter-wave inspection system was developed. An open-ended coaxial line sensor was used as a source and also a receiver of the millimeter-wave signal that was transmitted into and reflected from the packages. The phase of the reflection coefficient was measured for inspection of the delamination. The package was scanned in two perpendicular directions on a plane parallel to the package. A two-dimensional image was created by using the raw data of the millimeter-wave measurement. The millimeter-wave image showed almost the same features as that of scanning acoustic tomography; and the delamination was readily detected without using a coupling medium. Furthermore, a graph obtained by scanning the package in one direction along the center line of the package showed a higher sensitivity for distinguishing the delamination, thereby showing a potential for the on-line detection of delamination in an IC package.

Evaluation of inorganic matrixes as supports for immobilization of microbial lipase

Candida rugosa was immobilized by physical adsorption on several inorganic supports using hexane as coupling medium. The enzymatic activities of the different derivatives were determined by both hydrolysis of olive oil and esterification of n-butanol with butyric acid. The results were compared to previous data obtained by using a controlled porous silica matrix. The goal was to contribute in searching inexpensive supports for optimum lipase performance. All supports examined exhibited good properties for binding the enzyme lipase. Zirconium phosphate was the best support, giving the highest percentage of protein fixation (86%) and the highest retention of lipase activity after immobilization (34%). The operational stability performance for niobium oxide derivative was improved by previously activated the support with silane and glutaraldehyde. Thermal stabilities were also examined by thermal gravimetric analysis (TG).

Experimental study of construction mechanism of V(z) curves obtained by line-focus-beam acoustic microscopy

The propagation characteristics, viz., phase velocity and attenuation, of leaky surface acoustic waves (LSAWs), excited on the water/sample boundary are obtained through analyzing the V(z) curves measured by line-focus-beam acoustic microscopy. However, different values of these characteristics are obtained, depending upon different ultrasonic devices and operating frequencies employed. The construction mechanism of V(z) curves was investigated experimentally by measuring the amplitude and phase for Teflon to provide an understanding of the device performance for velocity measurements. A V(z) curve measured for Teflon, on which no leaky waves are excited when water is the coupling medium, can be used for the characteristic device response, depending only upon the device parameters and the operating frequencies. From the investigation of the ultrasonic device and the frequency dependences of the characteristic device responses, the phase gradient was found to be directly related to values of measured LSAW velocities. From this result, apparent frequency dependences in LSAW velocity measurements are explained quantitatively for a specimen of gadolinium gallium garnet.

The Complex Bonding of Titanium Nitride Layers in C/Mg Composites Revealed by ELNES Features

TiN interlayers in carbon fibre reinforced magnesium were investigated using high-resolution electron microscopy (HREM), scanning transmission electron microscopy (STEM) and electron energy loss spectroscopy (EELS), including analyses of near-edge fine structures (ELNES) and corresponding quantumchemical calculations. The nanocrystalline TiN fibre coatings of thicknesses between 10 and 30 nm were chemically vapour deposited from a TiCl4-N2-H2 atmosphere. Detailed ELNES measurements across the fibre/matrix interregion with a point-to-point distance of 1.3 nm in combination with quantumchemical calculations reveal in the fibre-near interlayer region interactions of the Ti-3d electrons with both the N-2p and the C-2p electrons resulting in mixed p-d-pi and p-d-sigma bondings. This hints to the formation of a TiC/TiN mixture of varying composition or of a titanium carbonitride (TiCxNy) with a high carbon content at the fibre/coating interface during the first steps of the coating by interaction of the carbon atoms of the fibre surface with the reactor gas. In this way the excellent adhesion of the TiN layers on the fibres can be understood which makes them appropriate for the important application in Mg matrices, where the layers have to serve as a suitable coupling medium between fibre and matrix.

The Complex Bonding of Titanium Nitride Layers in C/Mg Composites Revealed by ELNES Features

TiN interlayers in carbon fibre reinforced magnesium were investigated using high-resolution electron microscopy (HREM), scanning transmission electron microscopy (STEM) and electron energy loss spectroscopy (EELS), including analyses of near-edge fine structures (ELNES) and corresponding quantumchemical calculations. The nanocrystalline TiN fibre coatings of thicknesses between 10 and 30 nm were chemically vapour deposited from a TiCl 4 -N 2 -H 2 atmosphere. Detailed ELNES measurements across the fibre/matrix interregion with a point-to-point distance of 1.3 nm in combination with quantumchemical calculations reveal in the fibre-near interlayer region interactions of the Ti-3d electrons with both the N-2p and the C-2p electrons resulting in mixed p-d-π and p-d-σ bondings. This hints to the formation of a TiC/TiN mixture of varying composition or of a titanium carbonitride (TiC xNy) with a high carbon content at the fibre/coating interface during the first steps of the coating by interaction of the carbon atoms of the fibre surface with the reactor gas. In this way the excellent adhesion of the TiN layers on the fibres can be understood which makes them appropriate for the important application in Mg matrices, where the layers have to serve as a suitable coupling medium between fibre and matrix.

Seismic shear demand on wall segments of ductile coupled shear walls

This paper presents the results of nonlinear dynamic analyses carried out on ductile coupled shear walls (CSWs) to investigate the seismic shear demand on wall segments. The objectives of the present study were to evaluate the dynamic amplification and establish a code-format force reduction factor for shear, applicable in Canada. The study considered three Canadian seismic zones (4, 5, and 6), five numbers of storeys (6, 10, 15, 20, and 30), three degrees of coupling (low, medium, and high), and 10 historical earthquake records encompassing a broad range of frequency contents. Overall, 450 analyses were performed. Results indicate that the New Zealand amplification factor βv presently used in Canada overestimates the dynamic amplification. Additionally, the use of the overstrength factor for shear γp for tension walls may underestimate their shear resistance and result in a shear failure. Conversely, the use of γp for compression walls provided a reasonable factor of safety. Finally, for the shear design of CSWs, two alternative approaches are suggested. The first involves the use of a force reduction factor for shear, Rv, including the dynamic amplification factor γd and the overstrength factor γp as follows: Rv = 2.0 for Za > Zv, Rv = 1.0 for Za < Zv, and Rv = 1.3 for Za = Zv, where Za and Zv are acceleration- and velocity-related zonal identifiers. The second approach implies the use of the overstrength factor γp of the compression wall for both walls of CSWs and βv = 1.0.Key words: coupled shear walls, reinforced concrete, degree of coupling, seismic, frequency content, shear demand, dynamic amplification factor, force reduction factor for shear.

Microscopy

Microscopy

Ultrasonic measurement of enamel thickness: a tool for monitoring dental erosion?

Objectives: Wear of dental hard tissues, e.g. dental erosion, is reported to be a growing problem. A non-destructive measurement of enamel layer thickness would provide the opportunity for both early diagnosis, and longitudinal measurement of progressive enamel loss. It was the aim of this study to investigate the potential of ultrasonic pulse-echo measurements for the enamel thickness measurement. Methods: Nine extracted human incisor teeth were selected and stored in physiological saline. Mesial and distal tooth parts were removed, resulting in a central tooth slice of about 2 mm thickness. Where possible three buccal, and one palatal measuring sites were selected and indicated by pencil marks on one of the section planes. Ultrasonic pulse-echo measurements were made at each site using a Panametrics 25DL thickness gauge (Panametrics, Waltham, MA, USA), using a perspex delay line transducer (15 MHz) and glycerine coupling medium. Ultrasonic measurements were validated by measuring the thickness of the enamel layer at the marked side of the tooth slices with a light stereomicroscope at 120× magnification. Two observers performed independent measurements. Results: Limits of agreement for measurements by two observers ( n=42) were −0.09 and 0.09 mm. Measurements performed at 21°C and 34°C were not significantly different, as analysed by paired Student's t-test ( p=0.19). Pearson's correlation coefficient between ultrasonic and microscopic measurements was 0.90. Analysis of all measurements from both observers at both temperatures yielded a sound velocity in enamel of 6.5×10 3 m/s (standard error 0.1×10 3 m/s). Conclusions: It was concluded that the ultrasonic measurement of the enamel thickness is feasible without enamel preparation.

808 ミリ波による電子パッケージ内の非破壊評価

A nondestructive inspection system using millimeter-wave was developed for detection of delamination in IC packages. An open-ended coaxial line sensor was used as a source and also a receiver of millimeter-wave signal that was transmitted into and reflected from the packages. The phase of the reflection coefficient was measured for obtaining the information of the delamination. The package was scanned in two perpendicular directions on a plane parallel to the package. A two-dimensional image was created by using the raw data of the millimeter-wave measurement. The millimeter-wave image showed almost same feature as that of scanning acoustic tomography. The delamination was detected significantly without coupling medium. The millimeter-wave inspection system was proved to be a powerful tool for the integrity assessment of IC packages.

Compensator-based position control of an electrorheological actuator

This paper addresses the question of whether compensator-based controllers can be used to successfully control the position of a model scale robot arm attached to the output shaft of an electrorheological (ER) actuator, with a view of recommending the actuator for robotic applications and providing an alternative control strategy to proportional plus integral plus derivative, (PID), control. An ER actuator is a device that uses a ‘smart’ material, called an ER fluid or suspension, as a coupling medium between the prime mover running at a constant speed and a load. Three compensator-based controllers—the phase-lag, the phase-lead and lead-lag compensators—were designed and implemented on the ER actuator-arm system. The phase-lead and phase-lag compensators gave reasonable performance. The lead-lag compensator, on the other hand, was impossible to implement.

Ultrasonic testing of adhesive bonds of thin metal sheets

This article discusses the use of pulse-echo ultrasonic testing for the inspection of adhesive bonds between thin metal sheets (0.8 mm). The method is based on the measurement of the reflection coefficient at the metal/adhesive interface. After describing briefly the physical aspects of the phenomenon, an index is defined to detect defective zones of the joint (both for the lack of adhesive and for insufficient adhesion); the influence of the experimental variables (transducer frequency, coupling medium and contact force) on the measurement is discussed. The analysis shows that coupling medium and transducer frequency do not influence the results and that the method is robust with respect to the variation of contact force. By means of a control experiment it is shown that the statistical distribution of the index corresponding to good and defective adhesion zones are sufficiently separate to be distinguished. Finally, a procedure based on the statistical theory of decisions is proposed to evaluate the integrity of the joint under test.

Membrane-Based Laser Microdissection in Molecular Oncology

Background: PCR analysis of tumour-specific genomic alterations depends on the selective procurement of the tumour cells. Membrane-based microdissection, first described in 1992, has emerged as a valuable tool for the selective procurement of homogeneous cell populations from solid tumours, and provides good accuracy and correlation with standard histology. The incorporation of laser technology, either infra-red or ultra-violet, has further increased its impact. Material and Methods: The feasibility of microbeam MOMeNT ( Microdissection Of Membrane-mounted Native Tissue) is demonstrated with an emphasis on membrane type and coupling medium. Results: Microbeam MOMeNTis a reliable method for the detection of tumour-specific alterations when using PCR assays. Homozygous deletions in the MTS1/CDKN2tumour suppressor gene are demonstrated in bladder carcinomas. Ultra-thin (less than 2 μ) polyethylene terephthalate membranes and 70% ethanol as a coupling medium worked best in our hands. Conclusion: The re-evaluation of molecular markers of solid tumours may be necessary from microdissected material.