High‐intensity‐focused ultrasound and phase‐sensitive optical coherence tomography for high resolution surface acoustic wave elastography

Elastography has the ability of quantitatively evaluating the mechanical properties of soft tissue; thus it is helpful for diagnosis and treatment monitoring of many diseases, for example, skin diseases. Surface acoustic waves (SAWs) have been proven to be a non‐invasive, non‐destructive method for accurate characterization of tissue elastic properties. Current SAW elastography using high‐energy laser pulse or mechanical shaker still have some problems. In order to improve SAW elastography in medical application, a new technique was proposed in this paper, which combines high‐intensity‐focused ultrasound as a SAWs impulse inducer and phase‐sensitive optical coherence tomography as a SAWs detector. A 2% agar‐agar phantom and ex‐vivo porcine skin were tested. The data were processed by a new algorithm based on the Fourier analysis. The results show that the proposed method has the capability of quantifying the elastic properties of soft tissue‐mimicking materials. The lateral resolution of the elastogram has been significantly improved and the different layers in heterogeneous material could also been distinguished. Our improved technique of SAW elastography has a large potential to be widely applied in clinical use for skin disease diagnosis and treatment monitoring.      

Fabrication,Operation and Flow Visualization in Surface-acoustic-wave-driven Acoustic-counterflow Microfluidics

Surface acoustic waves (SAWs) can be used to drive liquids in portable microfluidic chips via the acoustic counterflow phenomenon. In this video we present the fabrication protocol for a multilayered SAW acoustic counterflow device. The device is fabricated starting from a lithium niobate (LN) substrate onto which two interdigital transducers (IDTs) and appropriate markers are patterned. A polydimethylsiloxane (PDMS) channel cast on an SU8 master mold is finally bonded on the patterned substrate. Following the fabrication procedure, we show the techniques that allow the characterization and operation of the acoustic counterflow device in order to pump fluids through the PDMS channel grid. We finally present the procedure to visualize liquid flow in the channels. The protocol is used to show on-chip fluid pumping under different flow regimes such as laminar flow and more complicated dynamics characterized by vortices and particle accumulation domains.     

CFD simulation of aerosol delivery to a human lung via surface acoustic wave nebulization

Administration of drug in the form of particles through inhalation is generally preferable in the treatment of respiratory disorders. Conventional inhalation therapy devices such as inhalers and nebulizers, nevertheless, suffer from low delivery efficiencies, wherein only a small fraction of the inhaled drug reaches the lower respiratory tract. This is primarily because these devices are not able to produce a sufficiently fine drug mist that has aerodynamic diameters on the order of a few microns. This study employs computational fluid dynamics to investigate the transport and deposition of the drug particles produced by a new aerosolization technique driven by surface acoustic waves (SAWs) into an in silico lung model geometrically reconstructed using computed tomography scanning. The particles generated by the SAW are released in different locations in a spacer chamber attached to a lung model extending from the mouth to the 6th generation of the lung bronchial tree. An Eulerian approach is used to solve the Navier–Stokes equations that govern the airflow within the respiratory tract, and a Lagrangian approach is adopted to track the particles, which are assumed to be spherical and inert. Due to the complexity of the lung geometry, the airflow patterns vary as it penetrates deeper into the lung. High inertia particles tend to deposit at locations where the geometry experiences a significant reduction in cross section. Our findings, nevertheless, show that the injection location can influence the delivery efficiency: Injection points close to the spacer centerline result in deeper penetration into the lung. Additionally, we found that the ratio of drug particles entering the right lung is significantly higher than the left lung, independent of the injection location. This is in good agreement with this fact that the most of airflow enters to the right lobes.     

Integration of a surface acoustic wave biosensor in a microfluidic polymer chip

SAW devices based on horizontally polarized surface shear waves (HPSSW) enable label-free, sensitive and cost-effective detection of biomolecules in real time. It is known that small sampling volumes with low inner surface areas and minimal mechanical stress arising from sealing elements of miniaturized sampling chambers are important in this field. Here, we present a new approach to integrate SAW devices with sampling chamber. The sensor device is encapsulated within a polymer chip containing fluid channel and contact points for fluidic and electric connections. The chip volume is only 0.9 microl. The polymeric encapsulation was performed tailor-made by Rapid Micro Product Development 3Dimensional Chip-Size-Packaging (RMPD 3D-CSP), a 3D photopolymerisation process. The polymer housing serves as tight and durable package for HPSSW biosensors and allows the use of the complete chips as disposables. Preliminary experiments with these microfluidic chips are shown to characterise the performance for their future applications as generic bioanalytical micro devices.     

Covalent bound sensing layers on surface acoustic wave (SAW) biosensors

This paper reports on the development of immunosensors based on commercially available surface acoustic wave (SAW) devices working at 380 MHz. Approaches for coating the sensor surface with a sensing layer of receptive biomolecules are presented and discussed. It was found that the sensitivity strongly relates to the immobilization method. Additionally, the sensitivity can be influenced by the density of accessible biomolecules on the active sensing area. Usually, by most of the standard immobilization procedures, two-dimensional layers of receptive biomolecules are obtained. We present a three-dimensional layer, which provides a higher absolute amount of recognition molecules. A dextran layer is photoimmobilized to the sensor surface and the recognition molecules are covalently embedded into the dextran matrix. The feasibility of specific immunosensing is investigated using SAW sensors connected to a fluid handling system.     

Model of the bacterial flagellar motor: response to varying viscous load.

A model of bacterial flagellar drive by cytomembrane streaming is described and applied to experiments of bacterial propulsion under varying viscous load. The theory predicts a linear dependence of the reciprocal propulsion velocity on the viscosity of the suspension medium, if the velocity of cytomembrane streaming far from the basal body of the flagella is assumed independent of the external viscosity. The theoretical predictions are in good agreement with experiments on free-swimming and on tethered bacteria. From comparison of the theory with experiments, the surface viscosity of the bacterial cytomembrane is evaluated for different bacterial species and turns out to be in the range observed experimentally on lipid monolayers.     

Cytoplasmic streaming inParamecium

Summary Certain species ofParamecium demonstrate rotational cytoplasmic streaming, in which most cytoplasmic particles and organelles flow along permanent route, in a constant direction. By means of novel methods of immobilization, observation and recording, some dynamic properties of cytoplasmic streaming have been described. It was found that the velocity profiles of coaxial layers of cytoplasm have a (parabolic) paraboidal shape and the mean output of cytoplasm flow in different examined zones of streaming is constant. As the consequence of randomly distributed elementary propulsion units within the cytoplasm, particles, which serve as markers of movement, exhibit movements of a saltatory nature; this form of movement is seen inParamecium streaming only in cases of error due to polarization of the saltating particles. Interaction of actin filaments and myosin is likely to occur under specific conditions in microcompartments of cytoplasm where local solations are generated eventually leading to contractions which might propagate on gelated neighbouring areas. Places of elementary contractions are scattered. Therefore the motile effect appears as streaming. Rotational cytoplasmic streaming inParamecium may serve as a convenient model for the study of the dynamics and function of cytoplasmic motility.     

A configuration scheme for connectivity-aware mobile P2P networks for efficient mobile cloud-based video streaming services

Mobile cloud-based video streaming services cannot be provided seamlessly when network traffic increases sharply in congested areas such as colleges, universities, and downtown at specific times. This paper proposes a configuration scheme for connectivity-aware P2P networks which can reduce network traffic of cloud-based streaming servers through sharing of streaming video by utilizing information on connectivity status of mobile devices, and which can improve the quality of mobile cloud-based video streaming services by considering mobility of mobile devices and QoS which have not been considered in existing P2P schemes. Our proposed scheme reduces the amount of server traffic and the disconnection times of mobile devices significantly, compared to the non-P2P scheme and the AODV scheme. It also increases considerably the number of mobile devices to which a cloud-based streaming server can provide video streaming services simultaneously, compared to the two schemes.     

Acoustic wave based MEMS devices for biosensing applications

This paper presents a review of acoustic-wave based MEMS devices that offer a promising technology platform for the development of sensitive, portable, real-time biosensors. MEMS fabrication of acoustic wave based biosensors enables device miniaturization, power consumption reduction and integration with electronic circuits. For biological applications, the biosensors are integrated in a microfluidic system and the sensing area is coated with a biospecific layer. When a bioanalyte interacts with the sensing layer, mass and viscosity variations of the biospecific layer can be detected by monitoring changes in the acoustic wave properties such as velocity, attenuation, resonant frequency and delay time. Few types of acoustic wave devices could be integrated in microfluidic systems without significant degradation of the quality factor. The acoustic wave based MEMS devices reported in the literature as biosensors and presented in this review are film bulk acoustic wave resonators (FBAR), surface acoustic waves (SAW) resonators and SAW delay lines. Different approaches to the realization of FBARs, SAW resonators and SAW delay lines for various biochemical applications are presented. Methods of integration of the acoustic wave MEMS devices in the microfluidic systems and functionalization strategies will be also discussed.     

Electrochemical characteristics of a hyperthermophilic enzyme in microdroplets stirred and heated by surface acoustic waves

Micro total analysis system (μTAS) is expected to be applied in various fields. In particular, since electrochemical measurement is inexpensive and easy, electrochemical measurement can be integrated with a microchannel. However, electrochemical detection sensitivity in a microchannel is lowered because the diffusion of the detection target is limited. In an ordinary electrochemical detection system, using a stirrer in a beaker can overcome limited diffusion. We previously proposed a new detection system that combines a microliquid solution agitation technology using surface acoustic waves (SAWs) with the μTAS. The SAWs function as microstirrers, thus making electrochemical detection possible by overcoming limited diffusion of the sample. However, when the solution is stirred by the SAWs, the temperature of the solution increases to 70°C due to vibrational energy. This leads to enzyme inactivation and impaired electrochemical response. Therefore, in this study, we used a hyperthermophile-derived enzyme. Temperature and electrochemical characteristics of the detection system using SAWs and a multi-copper oxidase (MCO) derived from the hyperthermophilic archaea Pyrobaculum aerophilum were studied. Laccase, which is an MCO derived from the thermophilic fungus Trametes versicolor, was also studied. We also characterized the enzyme-electrochemical reaction using SAWs by comparing the magnitude of the reduction current obtained using the two enzymes with different heat resistances. We observed an increase in the electrochemical response with the SAWs, without impaired enzyme activity. Thus, the use of a thermostable enzyme is suitable for the development of a biosensor that uses SAWs for agitation.     

SPR biosensing coupled to a digital microfluidic microstreaming system

This article reports on a proof-of-concept system composed of a droplet based surface plasmon resonance (SPR) system coupled to a surface acoustic wave (SAW) microfluidic plateform. It is now well established that surface based binding analyses such as SPR are highly influenced by the transport of analyte to the sensing surface. Further, obtaining reliable equilibrium in flow cells to realize quantification studies is not straightforward. An original solution compared to generally used pressure driven flows is then proposed to favourably cope with these issues. Efficiency of SAW microstreaming coupled to SPR biosensing is considered, in order to improve the accuracy of kinetic parameter estimation in mass transport limited regime and to realize reliable quantification studies. First, the droplet based SPR technique and its advantages are presented. Then, the integration of the microstreaming on the system is discussed. Streptavidin binding is then monitored in static mode and under SAW streaming mode.     

Force generation by cellular motors

Cell motility processes in non-muscle cells depend on the activity of motor proteins that bind to either microtubules or actin filaments. From presently available data it must be concluded that the driving force is generated by transient interaction of the respective motors with microtubules or actin filaments which then activates the binding and hydrolysis of ATP. This reaction results in an abrupt discharge of the motor molecule, the direction of which is determined by the spatial orientation of its binding to the helical and polar vehicle. The latter is thereby propelled in its length direction and simultaneously undergoes an axial rotation, while the expelled motor exerts an oppositely directed current in the surrounding fluid, comparable to jet propulsion. Force production, propulsion velocities and energy requirements known from in vitro studies comply with those derived from the theory. The theory opens new ways for the understanding of cellular activities such as particle transport, mitosis and morphodynamics.     

New immobilization method for SAW-biosensors: covalent attachment of antibodies via CNBr

Surface acoustic wave devices (SAWs) based on horizontally polarized shear waves can be used as mass-sensitive immunosensors. If the standard material, aluminium, is used for the interdigital transducers (IDTs) of these devices a pretreatment with a shielding layer of polyimide is necessary to prevent corrosion processes. However, this layer also prevents an easy covalent attachment of the necessary receptive molecules. Therefore, we developed a new activation method of this inert polyimide surface by treating with cyanogenbromide using the established cyano-transfer-technique. With a subsequent covalent attachment of anti-glucose oxidase (anti-GOD) a very sensitive SAW-immunosensor for glucose oxidase (GOD) can be obtained.     

Mechanisms of flagellar propulsion

Summary Flagellar propulsion takes place in the viscosity-dominated realm of low Reynolds number fluid dynamics. Volumes of fluid are carried in a capture zone around the moving regions of the flagellum, and the flagellar motion achieves propulsion because some of that water is shed from the capture zone, either from the flagellar tip in typical flagellar motion or to the side reached at the end of the effective stroke in the case of ciliary motion. Helical flagellar motion is in principle more efficient than planar beating, and the rotation caused by the former introduces complications in propulsion that may be advantageous, e.g., inEuglena, or disadvantageous, e.g., in a fixed cell. The presence of a surface near to the moving organelle restricts the fluid motion, but this effect enhances ciliary propulsion. There is a great variety of beat patterns, functionally adapted hydrodynamically or in other ways for locomotion, feeding, and other more restricted roles.Abbreviations Re Reynolds number - C_N coefficient of resistance to normal motion - C_T coefficient of resistance to tangential motion - l length - v velocity - fluid density - fluid viscosity - L an element of flagellar length moving at velocity V_L - V_W velocity of a wave - V_N velocity of element L in perpendicular (normal) direction - V_T velocity of element L in tangential direction - F_N force in normal direction - F_T force in tangential direction - F_P propulsive force - F_D drag force - E effective stroke - R recovery stroke - angular velocity of flagellum - angular velocity of body     

A study of protoplasmic streaming in Nitella by laser Doppler spectroscopy.

Laser light scattered from particles in the streaming protoplasm of a living cell is shifted in frequency by the Doppler effect. The spectrum of the scattered light can be measured and interpreted to infer details of the velocity distribution in the protoplasm. We have developed this approach to study the protoplasmic streaming in the fresh-water alga Nitella. Our results indicate a characteristic flow pattern to which diffusion makes a negligible contribution. No difference in the velocity of particles of different size is indicated. The streaming velocity linearly with temperature with a supraoptimal temperature of 34 degrees C, and the velocity distribution becomes narrower at high temperatures. The protoplasmic streaming can be inhibited by laser light, and this effect has been used to study the photoresponse of the algae. Using beam diameters of about 50 mum, we have shown that the inhibition is very local, becoming minimal at a displacement of about 200 mum in the upstream direction and 400 mum in the downstream direction. Prolonged exposure produces a bleached area free of chloroplasts, which is three orders of magnitude less sensitive to photoinhibition.     

The endogenous difference in the rates of acropetal and basipetal cytoplasmic streaming inChara rhizoids is enhanced by gravity

Summary Measurements of cytoplasmic streaming inChara rhizoids were made by a streak-photography method combined with dark-field illumination. The velocity of cytoplasmic streaming in the acropetal direction was faster than in the basipetal direction. The difference in the streaming velocities in both morphological directions was apparently due to endogenous forces. In addition to this, a small difference attributable to gravity was superimposed if the rhizoid was oriented parallel to the gravity vector. The difference in the endogenous forces underlying the oppositely directed streams may be as high as about 12-fold the force imposed by gravity but, on average, it is about 5-fold the gravity force. In the normal vertical position of the rhizoid, this endogenously generated difference is enhanced by the gravity effect. In contrast to the variability of streaming rate due to endogenous forces, the effect of the gravity force is relatively uniform. The difference between acropetal and basipetal streaming velocities is perpetuated over the whole range of lowered velocities after treatment with cytochalasin B. After prolonged incubation in cytochalasin B, the basipetal streaming stops earlier than the acropetal streaming. A difference in the length of filaments on both sides of the streaming machinery in rhizoids is proposed as the structural basis for the difference in velocities.     

Establishment of a biomimetic device based on tri-layer polymer actuators--propulsion fins

We propose to use bending type tri-layer polymer actuators as propulsion fins for a biomimetic device consisting of a rigid body, like a box fish having a carapace, and paired fins running through the rigid body, like a fish having pectoral fins. The fins or polymer bending actuators can be considered as individually controlled flexible membranes. Each fin is activated with sinusoidal inputs such that there is a phase lag between the movements of successive fins to create enough thrust force for propulsion. Eight fins with 0.125 aspect ratio have been used along both sides of the rigid body to move the device in the direction perpendicular to the longitudinal axis of the body. The designed device with the paired fins was successfully tested, moving in an organic solution consisting of solvent, propylene carbonate (PC), and electrolyte. The design procedure outlined in this study is offered as a guide to making functional devices based on polymer actuators and sensors.     

On the electric potentials inside a charged soft hydrated biological tissue: streaming potential versus diffusion potential

The main objective of this study is to determine the nature of electric fields inside articular cartilage while accounting for the effects of both streaming potential and diffusion potential. Specifically, we solve two tissue mechano-electrochemical problems using the triphasic theories developed by Lai et al. (1991, ASME J. Biomech Eng., 113, pp. 245-258) and Gu et al. (1998, ASME J. Biomech. Eng., 120, pp. 169-180) (1) the steady one-dimensional permeation problem; and (2) the transient one-dimensional ramped-displacement, confined-compression, stress-relaxation problem (both in an open circuit condition) so as to be able to calculate the compressive strain, the electric potential, and the fixed charged density (FCD) inside cartilage. Our calculations show that in these two technically important problems, the diffusion potential effects compete against the flow-induced kinetic effects (streaming potential) for dominance of the electric potential inside the tissue. For softer tissues of similar FCD (i.e., lower aggregate modulus), the diffusion potential effects are enhanced when the tissue is being compressed (i.e., increasing its FCD in a nonuniform manner) either by direct compression or by drag-induced compaction; indeed, the diffusion potential effect may dominate over the streaming potential effect. The polarity of the electric potential field is in the same direction of interstitial fluid flow when streaming potential dominates, and in the opposite direction of fluid flow when diffusion potential dominates. For physiologically realistic articular cartilage material parameters, the polarity of electric potential across the tissue on the outside (surface to surface) may be opposite to the polarity across the tissue on the inside (surface to surface). Since the electromechanical signals that chondrocytes perceive in situ are the stresses, strains, pressures and the electric field generated inside the extracellular matrix when the tissue is deformed, the results from this study offer new challenges for the understanding of possible mechanisms that control chondrocyte biosyntheses.     

Mathematical modelling of ciliary propulsion of an electrically-conducting Johnson-Segalman physiological fluid in a channel with slip

Bionic systems frequently feature electromagnetic pumping and offer significant advantages over conventional designs via intelligent bio-inspired properties. Complex wall features observed in nature also provide efficient mechanisms which can be utilized in biomimetic designs. The characteristics of biological fluids are frequently non-Newtonian in nature. In many natural systems super-hydrophobic slip is witnessed. Motivated by these phenomena, in this paper, we discussed a mathematical model for the cilia-generated propulsion of an electrically-conducting viscoelastic physiological fluid in a ciliated channel under the action of magnetic field. The rheological behavior of the fluid is simulated with the Johnson-Segalman constitutive model which allows internal wall slip. The regular or coordinated movement of the ciliated edges (which line the internal walls of the channel) is represented by a metachronal wave motion in the horizontal direction which generates a two-dimensional velocity profile. This mechanism is imposed by a periodic boundary condition which generates propulsion in the channel flow. Under the classical lubrication approximation, the boundary value problem is non-dimensionalized and solved analytically with a perturbation technique. The influence of the geometric, rheological (slip and Weissenberg number) and magnetic parameters on velocity, pressure gradient and the pressure rise (evaluated via the stream function in symbolic software) are presented graphically and interpreted at length.     

Cytoplasmic streaming in internodal cells ofNitella under centrifugal acceleration: a study done with a newly constructed centrifuge microscope

Summary We constructed a new centrifuge microscope of the stroboscopic type, with which the cytoplasmic streaming inNitella internodal cells under centrifugal acceleration was studied. Under moderate centrifugal acceleration (ca. 50–100×g), the direction of cytoplasmic streaming in an internodal cell ofNitella is parallel to the direction of the subcortical fibrils. The speed of endoplasm flowing contiguous to the subcortical fibrils is neither accelerated nor retarded by moderate centrifugal acceleration. The endoplasmic flow, however, stops suddenly following an electrical stimulus. The endoplasm contiguous to the subcortical fibrils is immobilized transiently at the time of streaming cessation induced by an electrical stimulus under centrifugal acceleration at 50–100×g, even at 900×g. It is suggested that transitory cross bridges between the immobilized endoplasm and the subcortical fibrils are formed at the time of streaming cessation. The bulk endoplasm flows as a whole in the direction parallel to that of the subcortical fibrils and stops promptly upon electrical stimulation. Soon after the stoppage the bulk endoplasm starts to flow passively in the direction parallel to that of the centrifugal acceleration as a result of the centrifugal force.Abbreviations APW artificial pond water - CMS centrifuge microscope