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During clinical procedures, the lithotripter shock wave (LSW) that is incident on the stone and resultant stress field is often asymmetric due to the respiratory motion of the patient. The variations of the LSW-stone interaction and associated fracture pattern were investigated by photoelastic imaging, phantom experiments, and three-dimensional fluid-solid interaction modeling at different lateral locations in a lithotripter field. In contrast to a T-shaped fracture pattern often observed in the posterior region of the disk-shaped stone under symmetric loading, the fracture pattern gradually transitioned to a tilted L-shape under asymmetric loading conditions. Moreover, the model simulations revealed the generation of surface acoustic waves (SAWs), i.e., a leaky Rayleigh wave on the anterior boundary and Scholte wave on the posterior boundary of the stone. The propagation of SAWs on the stone boundary is accompanied by a progressive transition of the LSW reflection pattern from regular to von Neumann and to weak von Neumann reflection near the glancing incidence and, concomitantly, the development and growth of a Mach stem, swirling around the stone boundary. The maximum tensile stress and stress integral were produced by SAWs on the stone boundary under asymmetric loading conditions, which drove the initiation and extension of surface cracks into the bulk of the stone that is confirmed by micro-computed tomography analysis.

The penetration depth of photoacoustic imaging in biological tissues has been fundamentally limited by the strong optical attenuation when light is delivered externally through the tissue surface. To address this issue, we previously reported internal-illumination photoacoustic imaging using a customized radial-emission optical fiber diffuser, which, however, has complex fabrication, high cost, and non-uniform light emission. To overcome these shortcomings, we have developed a new type of low-cost fiber diffusers based on a graded-scattering method in which the optical scattering of the fiber diffuser is gradually increased as the light travels. The graded scattering can compensate for the optical attenuation and provide relatively uniform light emission along the diffuser. We performed Monte Carlo numerical simulations to optimize several key design parameters, including the number of scattering segments, scattering anisotropy factor, divergence angle of the optical fiber, and reflective index of the surrounding medium. These optimized parameters collectively result in uniform light emission along the fiber diffuser and can be flexibly adjusted to accommodate different applications. We fabricated and characterized the prototype fiber diffuser made of agarose gel and intralipid. Equipped with the new fiber diffuser, we performed thorough proof-of-concept studies on ex vivo tissue phantoms and an in vivo swine model to demonstrate the deep-imaging capability (~10 cm achieved ex vivo) of photoacoustic tomography. We believe that the internal light delivery via the optimized fiber diffuser is an effective strategy to image deep targets (e.g., kidney) in large animals or humans.

Shock wave lithotripsy (SWL) has been widely used for non-invasive treatment of kidney stones. Cavitation plays an important role in stone fragmentation, yet it may also contribute to renal injury during SWL. It is therefore crucial to determine the spatiotemporal distributions of cavitation activities to maximize stone fragmentation while minimizing tissue injury. Traditional cavitation detection methods include high-speed optical imaging, active cavitation mapping (ACM), and passive cavitation mapping (PCM). While each of the three methods provides unique information about the dynamics of the bubbles, PCM has most practical applications in biological tissues. To image the dynamics of cavitation bubble collapse, we previously developed a sliding-window PCM (SW-PCM) method to identify each bubble collapse with high temporal and spatial resolution. In this work, to further validate and optimize the SW-PCM method, we have developed tri-modality cavitation imaging that includes three-dimensional high-speed optical imaging, ACM, and PCM seamlessly integrated in a single system. Using the tri-modality system, we imaged and analyzed laser-induced single cavitation bubbles in both free field and constricted space and shock wave-induced cavitation clusters. Collectively, our results have demonstrated the high reliability and spatial-temporal accuracy of the SW-PCM approach, which paves the way for the future in vivo applications on large animals and humans in SWL.

A damage model suggested by the Tuler–Butcher concept of dynamic accumulation of microscopic defects is obtained from experimental data on microcrack formation in synthetic kidney stones. Experimental data on appearance of microcracks is extracted from micro-computed tomography images of BegoStone simulants obtained after subjecting the stone to successive pulses produced by an electromagnetic shock-wave lithotripter source. Image processing of the data is used to infer statistical distributions of crack length and width in representative transversal cross-sections of a cylindrical stone. A high-resolution finite volume computational model, capable of accurately modeling internal reflections due to local changes in material properties produced by material damage, is used to simulate the accumulation of damage due to successive shocks. Comparison of statistical distributions of microcrack formation in computation and experiment allows calibration of the damage model. The model is subsequently used to compute fracture of a different aspect-ratio cylindrical stone predicting concurrent formation of two main fracture areas as observed experimentally.

Temperature mapping is essential in many biomedical studies and interventions to precisely control the tissue’s thermal conditions for optimal treatment efficiency and minimal side effects. Based on the Grüneisen parameter’s temperature dependence, photoacoustic (PA) imaging can provide relative temperature measurement, but it has been traditionally challenging to measure absolute temperatures without knowing the baseline temperature, especially in deep tissues with unknown optical and acoustic properties. Here, we report a new thermal-energy-memory-based photoacoustic thermometry (TEMPT). By illuminating the tissue with a burst of nanosecond laser pulses, TEMPT exploits the temperature dependence of the thermal energy lingering, which is probed by the corresponding PA signals acquired within the thermal confinement. A self-normalized ratiometric measurement cancels out temperature-irrelevant quantities and estimates the Grüneisen parameter. The temperature can then be evaluated, given the tissue’s temperature-dependent Grüneisen parameter, mass density, and specific heat capacity. Unlike the conventional PA thermometry, TEMPT does not require the knowledge of tissue’s baseline temperature, nor the optical properties. We have developed a mathematical model to describe the temperature dependence in TEMPT. We have demonstrated the feasibility of the temperature evaluation on tissue phantoms at 1.5 cm depth within a clinically relevant temperature range. Finally, as proof-of-concept, we applied TEMPT for temperature mapping during focused ultrasound treatment in mice in vivo at 2 mm depth. As a generic temperature mapping method, TEMPT is expected to find applications in thermotherapy of cancers on small animal models.

In this manuscript, we first describe the fabrication protocol of a microfluidic chip, with gold dots and fibronectin-coated regions on the same glass substrate, that precisely controls the generation of tandem bubbles and individual cells patterned nearby with well-defined locations and shapes. We then demonstrate the generation of tandem bubbles by using two pulsed lasers illuminating a pair of gold dots with a few-microsecond time delay. We visualize the bubble-bubble interaction and jet formation by high-speed imaging and characterize the resultant flow field using particle image velocimetry (PIV). Finally, we present some applications of this technique for single cell analysis, including cell membrane poration with macromolecule uptake, localized membrane deformation determined by the displacements of attached integrin-binding beads, and intracellular calcium response from ratiometric imaging. Our results show that a fast and directional jetting flow is produced by the tandem bubble interaction, which can impose a highly localized shear stress on the surface of a cell grown in close proximity. Furthermore, different bioeffects can be induced by altering the strength of the jetting flow by adjusting the standoff distance from the cell to the tandem bubbles.

Previous studies have demonstrated that stone comminution decreases with increased pulse repetition frequency as a result of bubble proliferation in the cavitation field of a shock wave lithotripter (Pishchalnikov et al 2011 J. Acoust. Soc. Am. 130 EL87-93). If cavitation nuclei remain in the propagation path of successive lithotripter pulses, especially in the acoustic coupling cushion of the shock wave source, they will consume part of the incident wave energy, leading to reduced tensile pressure in the focal region and thus lower stone comminution efficiency. We introduce a method to remove cavitation nuclei from the coupling cushion between successive shock exposures using a jet of degassed water. As a result, pre-focal bubble nuclei lifetime quantified by B-mode ultrasound imaging was reduced from 7 to 0.3 s by a jet with an exit velocity of 62 cm s(-1). Stone fragmentation (percent mass2 mm) after 250 shocks delivered at 1 Hz was enhanced from 22 ± 6% to 33 ± 5% (p = 0.007) in water without interposing tissue mimicking materials. Stone fragmentation after 500 shocks delivered at 2 Hz was increased from 18 ± 6% to 28 ± 8% (p = 0.04) with an interposing tissue phantom of 8 cm thick. These results demonstrate the critical influence of cavitation bubbles in the coupling cushion on stone comminution and suggest a potential strategy to improve the efficacy of contemporary shock wave lithotripters.

The dynamics, stabilization, and acoustic spectra of a bubble cluster in different liquids are investigated under the condition of ultrasonic cavitation. Experimental data for the dynamics of a spherical ultrasonic cluster near the end face of a rod, capillary, or pressure sensor placed in the antinode of a pressure standing wave at the center of a single-wave spherical piezoelectric concentrator (piezoelectric sphere) are presented. The variation of the cluster size with the parameters of the ultrasonic field and properties of the liquid is studied. It is found that the shape, collapse dynamics, and stability of the cavitation cluster have a significant influence on the acoustocapillary effect. It is shown that the maximal acoustocapillary effect and sonoluminescence are observed when a stable cluster with spherically symmetric collapse dynamics is provided at the end of a capillary in a 50% solution of glycerol. Using a small-size piezotransducer placed at the center of the sphere, the acoustic pressure is measured and acoustic spectra are studied for different voltages across the piezosphere and during the formation of variously shaped cavitation clusters. In the case of fully developed cavitation and a spherical cluster, the acoustic spectra contain subharmonic components, the cavitation noise factor rises to 35%, and the maximum of the noise envelope shifts toward higher frequencies.

The mechanism responsible for the development of autocyclic circular breakdowns in electrolyte as a result of the electric discharge within a hole in a dielectric plate has been experimentally studied. It is demonstrated that the breakdowns are caused by an axisymmetric electrohydrodynamic process involving the formation of a circular bubble breakdown, which acts as a current interrupter in the stage of expansion and as a switch in the stage of collapse, which is followed by the circular breakdown. On the whole, a self-adjusting antiphase process of bubble generation dynamics is developed in the system, whereby each preceding bubble collapses, in the field of pressure due to the subsequent bubble breakdown. This collapse proceeds at an accelerated rate and is accompanied by the fractionation of bubbles.

To elucidate mechanisms of cavitation action on a surface with microcapillary discontinuity and refine the model of the sonocapillary effect, the force acting on a cylinder is correlated with the height of a liquid in the capillary under cavitation, both quantities being measured at the same point of the ultrasonic field. It is found that the force acting on the cylinder is directed toward a cavitation cluster stabilized at the end face of the cylinder. This force can be enhanced with another cylinder placed on the side of the cluster coaxially with the first one. The dynamics of the cavitation cluster depending on the cylinder spacing is investigated in the case when one of the cylinders is on a pendulum suspension. The conditions for self-sustained oscillations of the pendulum are found. The dependence of the attracting force between the cylinders on the ultrasonic frequency and cylinder spacing is derived. The end-face-averaged pressure exerted on a cylinder of diameter 1.2 mm may reach 0.16 kPa, and the intracapillary pressure attains 0.89 kPa. Thus, the sonocapillary effect may be explained, at least partially, by a counterpressure arising from cluster-capillary interaction. This effect can be used in designing cavitation sensors and ultrasonic sources.

The determination of the phase of the bubble oscillation at the instant of light emission, which is a key issue for understanding the origin of cavitation luminescence of liquids, is discussed. The observation of luminescence in the course of the nucleation and growth of a bubble up to its collapse is performed in a bipolar wave consisting of a compression phase followed by a rarefaction phase in the regime of a two-fraction bubble cluster formation. The space-time distributions of the luminescence intensity and pressure and the dynamics of the cluster in water and a glycerin solution are investigated at the early stage of cavitation. A correlation between the maximal density of light flashes and the positive pressure pulses in the field of superposition of the initial and secondary cavitation compression waves is revealed. It is shown that the spherical focusing of acoustic pulses both away from the boundaries of the liquid and near its free surface makes it possible to compare the luminescence intensities for different rates of the pressure decrease.

The application of an electric discharge at numerous holes in a dielectric diaphragm for generating spherically focused shock waves in a salt solution is described. The design of the presented transducer makes the erosion of the electrodes impossible, since they are placed beyond the discharge zone; as a result, the point of focus stabilizes. The dependences on the discharge voltage, the number and total area of the holes in the diaphragm, and the electrolyte concentration are obtained for the pressure-wave amplitude at the focus; the extreme values are ∼40 and –12 MPa in the compression and rarefaction waves, respectively. The possibility of comminuting stones with masses of

Nonlinear processes accompanying the focusing of a microsecond acoustic pulse produced by an electromagnetic source shaped as a spherical segment are investigated. The processes are considered to be far from the boundaries of a liquid, in the absence of cavitation. Detailed measurements of the pressure field by a fiber-optic sensor and high-speed photography of the shock front are performed. The pressure field is found to be determined by the nonlinear effects that occur in the course of the propagation of the initial converging compression wave and an edge rarefaction wave. The peak pressure amplitudes at the focus are 75 and −42 MPa for the compression and rarefaction waves, respectively, at the maximum voltage of the pulse generator in use. The measured length of the compression wave front is equal to the response time of the sensor (8 ns). The pressure amplitude is shown to be limited by the irregularity of the propagation of a shock wave in the form of Mach’s disk. At the focus, the pressure gradient across the radiator axis reaches 0.5 atm/μm, while the diameter of the focal spot is 2.5±0.2 mm. The focus of the edge rarefaction wave formed due to diffraction is located closer to the radiator than the focus of the compression wave, which may facilitate the study of the biological effect of cavitation independently of the shear motion of the medium.

A transducer for measuring the velocity of shock wave propagation in salt water is described. The transducer operation is based on the depolarization of a double electrical layer exposed to an acoustic pulse. The time lag of the electrolysis current step at a disk anode was used for measuring the velocity of the propagation of the pressure disturbance. It was shown experimentally that the suggested method provides a measurement accuracy of 2% for the shock-wave front velocity, and base length of 5 mm. The transducer withstands repeated exposure to cavitation and shock waves at a pressure of up to 70 MPa.

The dynamics of luminescence generation and cavitation in the field of spherically focused and plane shock-acoustic waves in water, glycerin, and their mixtures is studied. It is shown that in the spherical focusing of shock-acoustic waves, the first pulse of luminescence correlates with cavitational rupture of the liquid. It is assumed that the registered luminescence is caused by electrokinetic processes upon formation and growth of cavitational bubbles.

A resonant plasma coiwerter for an atomie particie analyzer, created for an open magnetic trap AMBAL-M, is presented. A flow of charge-exchange atoms from the main plasma passes through a hydrogen plasma target, where they undergo partially the resonant charge-exchange and are transformed into posilive ions. High efficiency of the charge conversion in a wide energy range is reached, pollution of the main plasma by heavy impurities is excluded, the analyzed particles do not lose energy on acauiring the electric charge. The formed ion flow is analyzed for energy by a 30° electrostatic analyzer, and after accelerations are registered by a multichannel deteetor made on the MCP basis. Experimental researches of the plasma converter have shown that the chosen plasma are source providcs a controlled change of the target linear density in the range of (0.2–2) 1014cm−2 at low ion temperature and Frank Condon atomie concentration of hydrogen. It permits to reach high transformation efficiency of atoms into...

The performance of a newly developed light spot hydrophone (LSHD) in lithotripter field characterization was compared to that of the fiber optic probe hydrophone (FOPH). Pressure waveforms produced by a stable electromagnetic shock wave source were measured by the LSHD and FOPH under identical experimental conditions. In the low energy regime, focus and field acoustic parameters matched well between the two hydrophones. At clinically relevant high energy settings for shock wave lithotripsy, the measured leading compressive pressure waveforms matched closely with each other. However, the LSHD recorded slightly larger |P–| (p < 0.05) and secondary peak compressive pressures (p < 0.01) than the FOPH, leading to about 20% increase in total acoustic pulse energy calculated in a 6 mm radius around the focus (p = 0.06). Tensile pulse durations deviated ∼5% (p < 0.01) due to tensile wave shortening from cavitation activity using the LSHD. Intermittent compression spikes and laser light reflection artifacts have been correlated to bubble activity based on simultaneous high-speed imaging analysis. Altogether, both hydrophones are adequate for lithotripter field characterization as specified by the international standard IEC 61846.

The 3rd‐generation electromagnetic (EM) shock wave lithotripters often have narrow focal width and high peak pressure compared to the original Dornier HM‐3. In addition, the pressure waveform produced by a typical EM lithotripter has a secondary compressive wave following the tensile component that suppresses lithotripter pulse induced cavitation, which may impact negatively on stone comminution. These characteristic changes in the modern EM lithotripters may contribute in part to their reduced effectiveness observed clinically. To overcome these two drawbacks, we have designed a new acoustic lens for the Siemens Modularis EM lithotripter that produces an idealized pressure waveform similar to that of the HM‐3 with broad focal width and low peak pressure. At acoustic pulse energy of 53 mJ, the new lens design enlarges the −6 dB focal width of the Modularis by 47% while significantly reducing the second compressive wave in the lithotripter pulse throughout its focal plane. After 2000 shocks, in vitro commi...

The dynamic interaction between laser-generated tandem bubble and individual polystyrene particles of 2 and 10 μm in diameter is studied in a microfluidic channel (25 μm height) by high-speed imaging and particle image velocimetry. The asymmetric collapse of the tandem bubble produces a pair of microjets and associated long-lasting vortices that can propel a single particle to a maximum velocity of 1.4 m/s in 30 μs after the bubble collapse with a resultant directional displacement up to 60 μm in 150 μs. This method may be useful for high-throughput cell sorting in microfluidic devices.

Using a reflector insert, the original HM-3 lithotripter field at 20 kV was altered significantly with the peak positive pressure (p(+)) in the focal plane increased from 49 to 87 MPa while the -6 dB focal width decreased concomitantly from 11 to 4 mm. Using the original reflector, p(+) of 33 MPa with a -6 dB focal width of 18 mm were measured in a pre-focal plane 15-mm proximal to the lithotripter focus. However, the acoustic pulse energy delivered to a 28-mm diameter area around the lithotripter axis was comparable ( approximately 120 mJ). For all three exposure conditions, similar stone comminution ( approximately 70%) was produced in a mesh holder of 15 mm after 250 shocks. In contrast, stone comminution produced by the modified reflector either in a 15-mm finger cot (45%) or in a 30-mm membrane holder (14%) was significantly reduced from the corresponding values (56% and 26%) produced by the original reflector (no statistically significant differences were observed between the focal and pre-focal planes). These observations suggest that a low-pressure/broad focal width lithotripter field will produce better stone comminution than its counterpart with high-pressure/narrow focal width under clinically relevant in vitro comminution conditions.

The effect of beam size on stone comminution in the Dornier HM‐3 lithotripter were investigated using a modified reflector (MR), which was developed to produce an acoustic field with higher peak pressure and smaller beam size compared to the original reflector (OR) of the HM‐3. The acoustic fields produced at 20 kV by the MR in the focal plane, and by the OR in the focal and pre‐focal plane (z = −15 mm) were characterized using a light spot hydrophone. The efficiencies of stone comminution in a mesh holder were similar, but the corresponding values produced by using the MR in a membrane holder were significantly lower than those produced by the OR in the focal and pre‐focal planes. These results suggest that a broad beam size could increase stone comminution efficiency when fragments are spreading out or moving due to respiratory motion in a large area during SWL. In contrast, when stone fragments are confined and well aligned to lithotripter focus the beam size may not influence significantly the treatme...

Understanding the dynamics of bubble oscillation in tissue-constrained media such as within blood vessels is important for many current and potential therapeutic ultrasound applications. Cavitation is a primary mechanism responsible for vessel rupture and tissue injury in shock wave lithotripsy [1]. In sonoporation cavitation can be used to increase permeability of biological membranes. Particularly, ultrasound contrast agents are widely used for imaging of blood vessels and for enhancement of ultrasound-mediated gene delivery [2]. Modeling of non-linear oscillations of bubbles in acrylic capillaries in a high-intensity focused ultrasound field revealed a clear dependence of bubble displacement and fragmentation on tube diameter [3]. However, the effect of elastic boundary on bubble dynamics may differ significantly from that of a rigid boundary [4, 5]. In this study, experimental investigation of the dynamics of bubble oscillation in an elastic tube was performed and preliminary results from tubes of different inner diameters are presented.Copyright © 2007 by ASME

A previously introduced model for stone comminution in shock wave lithotripsy is extended to include damage produced by cavitation. At the macroscopic, continuum level a 3D elasticity model with time-varying material constants capturing localized damage provides the overall stress field within kidney stone simulants. Regions of high stress are identified and a mesoscopic crack propagation is used to dynamically update localized damage. The crack propagation model in turn is linked with a microscopic grain dynamics model. Continuum stresses and surface pitting is provided by a multiscale cavitation model (see related talk). The overall procedure is capable of tracking stone fragments and surface cavitation of the fragments through several levels of breakdown. Computed stone fragment distributions are compared to experimental results. [Work supported by NIH through 5R37DK052985-18.]

Cavitation damage is responsible for initial pitting of kidney stone surfaces, damage that is thought to play an important role in shock wave lithotripsy. We introduce a multiscale model of the formation of cavitation bubbles in water, and subsequent breakdown. At a macroscopic, continuum scale cavitation is modeled by the 3D Euler equations with a Tait equation of state. Adaptive mesh refinement is used to provide increased resolution at the liquid/vapor boundary. Cells with both liquid and vapor phases are flagged by the continuum solver for mesoscale, kinetic modeling by a lattice Boltzmann description capable of capturing non-equilibrium behavior (e.g., phase change, energetic jet impingement). Isolated and interacting two-bubble configurations are studied. Computational simulation results are compared with high-speed experimental imaging of individual bubble dynamics and bubble–bubble interaction. The model is used to build a statistical description of multiple-bubble interaction, with input from cavitation cloud imaging. [Work supported by NIH through 5R37DK052985-18.]

A challenge in clinical shock wave lithotripsy (SWL) is stone translation due to a patient’s respiratory motion, in a direction perpendicular to shockwave propagation, which may negatively affect stone comminution while increasing the risk of tissue injury. We have developed a method using external masks and a modified lens geometry to transform the axisymmetric pressure distribution in the focal plane of an electromagnetic lithotripter into a non-axisymmetric elliptical distribution. At equivalent acoustic pulse energy (46 mJ), the peak pressure was reduced from 44 MPa to 38 MPa while the −6 dB focal width was increased from 7.4 mm for the original to 11.7 mm (major axis) and 7.9 mm (minor axis) of the modified field. In vitro stone comminution was performed in a tube holder (d = 14 mm) using a translation pattern with 12 breaths per minute and 15 mm in excursion distance. Stone comminution after 1000 shocks are 71.2 ± 4.4% and 65.2 ±8.3% (p

Previous research shows that a shockwave’s tensile phase can be strongly attenuated as a function of gas concentration in the coupling medium. Here, we seek to elucidate the relationship between tensile attenuation and gas concentration via pressure measurements at the focus and highspeed imaging. By performing in vitro experiments with water of varying gas concentrations (2.05 mg/L, 4.30 mg/L, and 6.50 mg/L), the negative impulsive pressure is correlated to the density of the bubble cloud that occurs in the beampath. It is found that for gas contents below 4 mg/L the bubble cloud remains sparse and the shockwave’s tensile phase is successfully transmitted with no loss in impulsive pressure. For gas contents 4 mg/L and above the bubble cloud becomes highly dense and prevents transmission with up to a 75% loss in impulsive pressure. Corresponding stone comminution experiments show that the treatment efficiency sharply decreases with increasing gas concentration. These results underlie the importance of degassing the water used in the coupling medium before treatment.

To assess the role of stress waves and cavitation in comminuting residual fragments during shock wave lithotripsy (SWL), cylindrical 4 × 4 mm BegoStone phantoms were treated in an electromagnetic lithotripter either at the focus (z = 0, p+ = ∼45 MPa) or pre-focally (z = −30 mm, p+ = ∼24 MPa). The treatment was performed with the stone immersed either in degassed water or in Butanediol, which has similar acoustic impedance to water but much higher viscosity to suppress cavitation. At the focus, the first fracture was observed after 26 ± 9 shocks, both in water and Butanediol (p = 0.7). However, when stones were moved pre-focally where comparable cavitation is produced (based on high speed imaging), the average shock number required for the initial fracture was increased to 66 ± 10 in water and 122 ± 20 in Butanediol (p = 0.002). Below −40 mm prefocally (p+

Understanding the dynamic interaction of cavitation bubbles with biological tissue is central to the effective and safe application of therapeutic ultrasound in clinical medicine. Coupled oscillation of two laser generated microbubbles (maximum radius = 28 μm) in constrained media and associated shear stresses are investigated experimentally. Bubble‐bubble interaction in a microchannel of 25‐μm height is observed using high‐speed video cameras and μPIV technique. Two liquid micro‐jets moving in opposite directions can be generated when the second bubble is produced at the maximum size of the first one. The interaction of these tandem microbubbles with single cell leads to controllable poration of adjacent cell membrane and dye uptake. Micro‐PIV data are compared with cell viability at various bubble‐cell distances and azimuthal orientations. This method provides a new approach for highly selective cell treatment in situ applicable to targeted microinjection of macromolecules and gene vectors in microfluid...

Coupled oscillations of two adjacent laser‐induced microbubbles have been shown to produce unique asymmetric bubble deformation and microjet formation. The resultant microstreaming and shear stress can cause localized cell membrane poration with potential application in targeted drug and gene delivery. In this study, we investigate the bubble dynamics and flow field produced by laser‐generated tandem microbubble in a microfluidic device. Flow field around the tandem microbubble is analyzed with respect to phase delay, inter‐bubble distance, and size ratio between the two microbubbles. In addition, micropatterning technique is used to control the adhesion site and growth pattern of HeLa cells in relation to the tandem microbubble. Flow vorticity is observed to be a key parameter that correlates with the strength of tandem microbubble oscillation and resultant macromolecule uptake efficiency. [Work supported by NIH Grant Nos. R01DK052985, R21CA135221, and S10RR016802].

Slow variation (for 10–40 min) of the electrical conductivity of a water cell in weak permanent magnetic fields was studied. Relaxation characteristics and the dependence of the resistivity on a magnetic field ranging between 0.02 and 0.11 G were obtained. It was found that the cell response lags behind magnetic field switching-on and switching-off.

Coupled oscillation of two laser generated microbubbles (maximum radius = 28 μm) and associated shear stresses are investigated experimentally. Bubble‐bubble interaction in a microchannel of 25 μm height is observed using high‐speed video cameras and μPIV technique. Two liquid microjets moving in opposite directions can be generated when the second bubble is produced at the maximum size of the first one. The interaction of these tandem microbubbles with single cell leads to controllable poration of adjacent cell membrane and dye uptake. μPIV data are compared with cell viability at various bubble‐cell distances and azimuthal orientations. This method provides a new approach for highly selective cell treatment in situ, applicable to targeted microinjection of macromolecules and gene vectors in microfluidics devices. [Work supported in part by NIH.]

Recent studies have highlighted the potential for using laser‐induced micro‐cavitation in lab‐on‐a‐chip devices. Shear stress in a liquid can be controlled and significantly enhanced by bubble‐bubble interaction, providing new options for in situ cell treatment. Two micro‐bubbles (10 μs life time) are generated in a 25‐μm liquid layer using 5 ns tandem laser pulses delivered through the objective of a microscope. Bubble‐bubble interaction in nearly two‐dimensional flow is observed using high‐speed video cameras. Two liquid micro‐jets moving in opposite directions can be generated when the second bubble is produced at the maximum size of the first one. The jet velocity is estimated about 35 m/s. Particle imaging velocimetry reveals vortex flow motion around the oscillating bubble lasting for about 200 μs. Cell lyses produced by jetting from asymmetric oscillation of tandem microbubbles are investigated at various bubble‐cell distances and compared with the results from single symmetric bubble oscillation. ...

Results are presented of experimental investigations of the dynamics of the electrical conductivity of an electrolyte when one of the electrodes is exposed to a weak shock pulse. It is shown that the electrical conductivity in the cell increases as a result of damage to the electric double layer.