Biomedical subjects
Publications and source records attributed to Junru Wu.
An experimental study using a mason horn of 21.4 kHz indicated that the threshold shear stress for cell sonoporation was 12+/-4 Pa for ultrasound exposure time up to 7 min. Numerical calculations have shown that shear stress associated with microstreaming surrounding encapsulated bubbles may be large enough to generate sonoporation at 0.1 MPa of 1 or 2 MHz ultrasound.
It has been shown experimentally in cell suspensions that sonoporation could be used to deliver the anti-cancer drug Adriamycin hydrochloride (ADR) into Jurkat lymphocytes and that it could also be used to deliver goat anti-rabbit IgG and anti-mouse IgD, antibodies into human peripheral blood mononuclear cells (PBMC) and Jurkat lymphocytes. When ADR was delivered, the delivery efficiency reached 4.80+/-2.04% and control baseline (no ultrasound and no ADR) was 0.17+/-0.14%. When anti-rabbit IgD was delivered, the efficiencies were 34.90+/-1.80% (control baseline was 1.33+/-0.31%) and 32.50+/-4.36% (control baseline was 1.66+/-0.06%) respectively for Jurkat cells and PBMC. When goat anti-rabbit IgG was delivered, the efficiencies were 78.60+/-3.60% (control baseline was 1.60+/-0.00%) and 57.50+/-4.23% (control baseline was 11.30+/-0.81%) respectively for Jurkat cells and PBMC.
It is known that microscopic spherulite growth plays an important role in macroscopical properties such as elastic moduli of some semicrystalline polymers. Ultrasonic spectroscopy can be used to quantitatively determine the role of spherulites. As a first approximation, spherulitic polymers are modeled as a material with spherical inclusions in an amorphous matrix. This two-phase composite model is then physically realized by embedding glass micro-spheres in an epoxy. The dynamic mechanical properties of these composites are experimentally determined by measuring their acoustic properties such as phase velocity and attenuation. Acoustic scattering theories are then applied to this model to test their predictive capabilities for the real composite's mechanical properties.
A method to prepare liposomes is presented. Liposomes made in our laboratory were characterized acoustically and optically. The phase velocity and attenuation of liposomes in suspension (concentration = 10(9)/mL) were measured, ranging from 2 to 14 MHz, using ultrasound spectroscopy. Anti-rabbit IgG conjugated with Alexafluor 647 was delivered into Jurkat cells in suspension, using the liposomes, by 10 % duty cycle ultrasound tonebursts of 2.2 MHz (the in situ spatial peak-pressure amplitude = 80 W/cm2) with an efficiency of 13 %. It has been experimentally shown that liposomes may be an alternative stable agent to Optison for delivering macromolecules into cells.
Water chestnut (Trapa natans L.), an annual aquatic plant with floating leaves was first introduced into North America in 1874. Since then, wild populations have quickly become established in many locations within Northeastern USA. Due to its detrimental effects on the overall health of aquatic ecosystems, millions of dollars have been spent to control the water chestnut infestations in the North America through mechanical harvesting and manual removal, with limited success. The potential for continued expansion of the infestations demonstrates an urgent need for an effective control method. This study examined the potential of ultrasound application as an alternative control strategy for water chestnut management. Various frequencies and amplitudes of ultrasound generated by submerged transducers were applied directly to water chestnuts harvested from Lake Champlain. Substantial damages on water chestnut cells as well as penetrated petitoles were observed at the following tested frequencies of ultrasound, 20 kHz, 187 kHz, 469 kHz, 519 kHz and 2.34 MHz. Among them, 20 kHz ultrasound of 1.9 MPa acoustic pressure amplitude demonstrated the most significant damages within 10 s of ultrasound exposure. The treated plants started to die within 72 h and the mortality rate of water chestnut plants treated with the ultrasound application was 100%.
Nonthermal technologies are emerging as promising alternatives to heat treatment for food processing. Ultrasound, defined as sound waves with a frequency greater than 20 kHz, has proven bactericidal effects, especially when combined with other microbial-reduction strategies such as mild heating. In this study, ultrasound treatment (sonifier probe at 20 kHz, 100% power level, 150 W acoustic power, 118 W/cm2 acoustic intensity) with or without the effect of mild heat (57 degrees C) was effective at reducing microbial levels in raw milk, Listeria monocytogenes levels inoculated in ultrahigh-temperature milk, and Escherichia coli O157:H7 in apple cider. Continuous flow ultrasound treatment combined with mild heat (57 degrees C) for 18 min resulted in a 5-log reduction of L. monocytogenes in ultrahigh-temperature milk, a 5-log reduction in total aerobic bacteria in raw milk, and a 6-log reduction in E. coli O157:H7 in pasteurized apple cider. Inactivation regressions were second-order polynomials, showing an initial period of rapid inactivation, eventually tailing off. Results indicate that ultrasound technology is a promising processing alternative for the reduction of microorganisms in liquid foods.
BACKGROUND: Acupuncture points and meridians are commonly believed to possess unique electrical properties. The experimental support for this claim is limited given the technical and methodological shortcomings of prior studies. Recent studies indicate a correspondence between acupuncture meridians and connective tissue planes. We hypothesized that segments of acupuncture meridians that are associated with loose connective tissue planes (between muscles or between muscle and bone) visible by ultrasound have greater electrical conductance (less electrical impedance) than non-meridian, parallel control segments. METHODS: We used a four-electrode method to measure the electrical impedance along segments of the Pericardium and Spleen meridians and corresponding parallel control segments in 23 human subjects. Meridian segments were determined by palpation and proportional measurements. Connective tissue planes underlying those segments were imaged with an ultrasound scanner. Along each meridian segment, four gold-plated needles were inserted along a straight line and used as electrodes. A parallel series of four control needles were placed 0.8 cm medial to the meridian needles. For each set of four needles, a 3.3 kHz alternating (AC) constant amplitude current was introduced at three different amplitudes (20, 40, and 80 microAmps) to the outer two needles, while the voltage was measured between the inner two needles. Tissue impedance between the two inner needles was calculated based on Ohm's law (ratio of voltage to current intensity). RESULTS: At the Pericardium location, mean tissue impedance was significantly lower at meridian segments (70.4 +/- 5.7 Omega) compared with control segments (75.0 +/- 5.9 Omega) (p = 0.0003). At the Spleen location, mean impedance for meridian (67.8 +/- 6.8 Omega) and control segments (68.5 +/- 7.5 Omega) were not significantly different (p = 0.70). CONCLUSION: Tissue impedance was on average lower along the Pericardium meridian, but not along the Spleen meridian, compared with their respective controls. Ultrasound imaging of meridian and control segments suggested that contact of the needle with connective tissue may explain the decrease in electrical impedance noted at the Pericardium meridian. Further studies are needed to determine whether tissue impedance is lower in (1) connective tissue in general compared with muscle and (2) meridian-associated vs. non meridian-associated connective tissue.
A fundamental mathematical framework for applications of Doublet Mechanics to ultrasound propagation in a discrete material is introduced. A multiscale wave equation, dispersion relation for longitudinal waves, and shear waves are derived. The van Hove singularities and corresponding highest frequency limits for the Mth-order wave equations of longitudinal and shear waves are determined for a widely used microbundle structure. Doublet Mechanics is applied to soft tissue and low-density polyethylene. The experimental dispersion data for soft tissue and low-density polyethylene are compared with results predicted by Doublet Mechanics and an attenuation model based on a Kramers-Kronig relation in classical continuum mechanics.
The mathematical framework of a new elastic theory-doublet mechanics (DM)-was reviewed. The fundamental difference between DM and classical continuum mechanics (CCM) is that the former has taken the discrete nature of tissue on the cellular level into account and the latter assumes tissue is uniform and continuous. Theoretical calculations based on DM were performed for reflection coefficients of a substrate-tissue layer-substrate assembly. Results of computer simulations have shown that ultrasound reflection coefficients in the range of 15-30 MHz are sensitive to changes in cell size and elastic moduli of tissue according to DM but not to CCM. Potential experimental applications of this technique to tissue characterization are discussed.
The nonlinear properties of an encapsulated microbubble of a contrast agent were studied theoretically and experimentally. A modified nonlinear differential equation (Herring equation) was used to describe the radial oscillation of the microbubble and solved numerically. It was found that the nonlinear resonance frequency, at which the peak radial oscillation amplitude occurs, was a decreasing function of the acoustic amplitude of a driving ultrasonic pulse. Optical images of the contrast agent microbubbles under various ultrasonic exposure conditions: 1. sham exposure; 2. 2-MHz spatial peak acoustic pressure = 200 kPa, I(SATA) = 260 mW/cm(2), duty cycle = 7.5%, repetition period = 0.0266 ms; 3. 0.5-MHz spatial peak acoustic pressure = 200 kPa, I(SATA) = 130 mW/cm(2), duty cycle = 7.5%, repetition period = 0.1067 ms; have also shown that the lower-frequency ultrasound (US) excitation (0.5 MHz) is more effective in disruption of the microbubbles due to acoustic inertial cavitation than the higher frequency US (2 MHz).
Subcutaneous tissue is part of a bodywide network of "loose" connective tissue including interstitial connective tissues separating muscles and surrounding all nerves and blood vessels. Despite its ubiquitous presence in the body and its potential importance in a variety of therapies utilizing mechanical stretch, as well as normal movement and exercise, very little is known about loose connective tissue's biomechanical behavior. This study aimed to determine elastic and viscoelastic mechanical properties of ex-vivo rat subcutaneous tissue in uniaxial tension with incremental stress relaxation experiments. The elastic response of the tissue was linear, with instantaneous and equilibrium tensile moduli of 4.77 kPa and 2.75 kPa, respectively. Using a 5 parameter Maxwell solid model, material parameters micro(1) = 0.95 +/- 0.24 Ns/m and micro(2) = 8.49 +/- 2.42 Ns/m defined coefficients of viscosity related to time constants tau(1M) = 3.83 +/- 0.15 sec and tau(2M) = 30.15 +/- 3.16 sec, respectively. Using a continuous relaxation function, parameters C = 0.25 +/- 0.12, tau(1C) = 1.86 +/- 0.34 sec, and tau(2C) = 110.40 +/- 25.59 sec defined the magnitude and frequency limits of the relaxation spectrum. This study provides baseline information for the stress-strain behaviors of subcutaneous connective tissue. Our results underscore the differences in mechanical behaviors between loose and high-load bearing connective tissues and suggest that loose connective tissues may function to transmit mechanical signals to and from the abundant fibroblasts, immune, vascular, and neural cells present within these tissues.
Acupuncture needle manipulation gives rise to "needle grasp," a biomechanical phenomenon characterized by an increase in the force necessary to pull the needle out of the tissue (pullout force). This study investigates the hypothesis that winding of connective tissue, rather than muscle contraction, is the mechanism responsible for needle grasp. We performed 1) measurements of pullout force in humans with and without needle penetration of muscle; 2) measurements of pullout force in anesthetized rats, with and without needle rotation, followed by measurements of connective tissue volume surrounding the needle; 3) imaging of rat abdominal wall explants, with and without needle rotation, using ultrasound scanning acoustic microscopy. We found 1) no evidence that increased penetration of muscle results in greater pullout force than increased penetration of subcutaneous tissue; 2) that both pullout force and subcutaneous tissue volume were increased by needle rotation; 3) that increased periodic architectural order was present in subcutaneous tissue with rotation, compared with no rotation. These data support connective tissue winding as the mechanism responsible for the increase in pullout force induced by needle rotation. Winding may allow needle movements to deliver a mechanical signal into the tissue and may be key to acupuncture's therapeutic mechanism.
Numerical calculations have shown that shear stress associated with microstreaming surrounding encapsulated stable bubbles of contrast agents, near living cells driven by 0.12-MPa acoustic pressure amplitude ultrasound (US) at 1 MHz or 2 MHz, may be large enough to generate reparable sonoporation of the cells. Some encapsulated bubbles that have mechanically weak shells may break into free bubbles under the above-mentioned sound field. When that happens, the shear stress caused by microstreaming surrounding the free bubble increases dramatically and may play an important role in lethal sonoporation and fragmentation of cells during the early stage of US exposure.
A feasibility study of using high-amplitude ultrasound (US) to deliver large molecules transdermally was undertaken. US (20 kHz) of intensity in the range between 2 to 50 W/cm(2) was used to increase the permeability of skin in vitro to large size molecules. For example, when 20-kHz, 5% duty cycle US at the spatial average and pulse-average intensity I(SAPA) = 19 W/cm(2) was applied for 10 min and the distance between the US source and the surface of a skin specimen was 2 mm, the skin permeability was calculated to be 0.5 +/- 0.2 cm/h and 8.5 +/- 4.2 cm/h, respectively, for poly l-lysine-fluorescein isothiocyanate (FITC) (51 kDa) and octa-1-lysine-FITC (2.5 kDa). Without application of US, the skin permeability of the above-mentioned molecules would be essentially zero. A transdermal flux enhancement occurring during the process reported here was much higher than that due to sonophoresis (I(SAPA) < 2 W/cm(2)) as reported in the literature. For comparison, for example, the skin permeability for delivering erythropoeitin (48 kDa) and insulin (6 kDa) reached 9.8 x 10(-6) and 3.3 x10(-3) cm/h, respectively, by using sonophoresis for 1 h US exposure. Experimental results from transdermal flux kinetics, and confocal microscopic cross-sectional and optical images, suggested that the formation of pores in the stratum corneum, whose size varies with skin samples, may be in the range of 1 to 100 microm. The confocal images also suggest the formation of microm-size pathways in epidermis during US exposure.
Reparable sonoporation was observed in Jurkat lymphocytes in suspension exposed to a vibrating Mason horn tuned to 21.4 KHz. The diameter of the horn tip was 400 microm and its transverse displacement amplitude was 7.8 microm. It was found that the shear stress associated with microstreaming surrounding the Mason-horn tip was the primary reason for the cell reparable sonoporation. The threshold shear stress was determined to be 12 +/- 4 Pa for exposure time up to 7 min. It was also found that the shorter the exposure time, the greater the threshold.
Explore the source record for details and available documents.