Visually controlled pulsatile release of insulin from chitosan poly-acrylic acid nanobubbles triggered by focused ultrasound.

Insulin therapy is the most effective way to control the blood glucose value of diabetic patients. The most effective administration route for insulin is subcutaneous injection because bioavailability for non-injection administration is low and unstable. However, patients often need a multiple daily insulin injection regimen to control basal and postprandial blood glucose, which causes various complications. Controlled pulsatile drug release technology using ultrasound as an external stimulus source is a very promising method to avoid multiple injections of insulin. However, most of the drug-loaded microbubbles used for ultrasound-mediated treatment have a short half-life, which limits their use in controlled pulsatile drug release. More importantly, how to control insulin release is still a challenge. In this paper, chitosan poly-acrylic acid nanobubbles as drug carriers of insulin were prepared to achieve a visually controlled pulsatile release of insulin triggered by focused ultrasound. The experimental results in vivo demonstrated that nanobubbles were stable enough to achieve long-term visualization for 7 days after intramuscular injection in rats. Under the guidance of ultrasound imaging, it is visible to find the position and observe the gray values change of nanobubbles. Thus, when triggered by focused ultrasound, the amount of insulin could be accurately pulsatile released from nanobubbles. In vivo experiments in rats showed that the visually controlled pulsatile release of insulin could be achieved for a long time, up to 3 consecutive days. The blood glucose level could be repeatedly reduced by focused ultrasound irradiation with just one injection. Our research provided a promising way for visually controlled pulsatile release of insulin, which would significantly reduce the injection frequency of insulin.

An ultrasensitive solid-state ECL biosensor based on synergistic effect between Zn-NGQDs and porphyrin-based MOF as "on-off-on" platform.

To develop an ultra-sensitive solid-state electrochemiluminescence (ECL) biosensor for detection of miRNA 24, three different forms of porphyrin metal-organic framework (MOF) nanomaterials with good biocompatibility were synthesized through small molecule ligand modulation. We investigated various properties of synthesized MOFs in the presence of different small molecule ligands. The as-obtained 2D MOF nanodisk exhibited high ECL intensity and outstanding stability in the presence of a co-reactant at low concentrations. We also synthesized zinc-based quantum dots (Zn-NGQDs) with excellent photovoltaic properties by doping zinc dithiothreitol (DTT-Zn) into quantum dots. Accordingly, an enzyme-free solid-state ECL biosensor for miRNA 24 based on the "on-off-on" signal conversion strategy was created. Dependent on the synergy between the luminophor 2D MOF and Zn-NGQDs, the biosensor achieves a wide linear range from 1.00 × 10-16 to 1.00 × 10-10 mol·L-1 and an exceedingly low detection limit of 0.03 fM. Furthermore, the ECL biosensor exhibits outstanding selectivity, repeatability, and stability. The method has great potential for investigating sensitive detection models for various biomolecules and the design of highly efficient MOF luminescent materials.

Wireless Power Transmission for Implantable Medical Devices Using Focused Ultrasound and a Miniaturized 1-3 Piezoelectric Composite Receiving Transducer.

Wireless power transmission (WPT) using ultrasound is a promising way for wirelessly recharging implantable medical devices (IMDs). However, the transmitted power using ultrasound so far is insufficient for driving the existing IMDs. Moreover, the size of the receiving transducer is larger, which is not suitable for implantation. To increase the output power and reduce the size of the implantable receiver, this article presents a method of combining focused ultrasound with a miniaturized 1-3 piezoelectric composite receiving transducer to produce higher electrical power. An analytical fluid-structure interaction model is constructed to fully understand the operating mechanism of the receiving transducer under ultrasonic force. In our experiments, a miniaturized 1-3 piezoelectric composite receiving transducer with a diameter of 3.7 mm was used. The output power generated from the receiving transducer reached 60 mW at a distance of 150 mm. In vitro and in vivo animal experiments proved that the miniaturized transducer could successfully receive focused ultrasonic energy and convert it to electrical power. The method presented and the electrical power that we obtained can provide a valuable reference for wirelessly charging of IMDs.

Fabrication of Lipid Nanotubules by Ultrasonic Drag Force.

This work reports a new method of fabricating lipid nanotubules using ultrasonic Stokes drag force in theory and experiment. Ultrasonic Stokes drag force generated using a planar piezoelectric ultrasonic transducer in a remotely controllable way is introduced. When ultrasonic Stokes drag force is applied on lipid vesicles, the lipid nanotubules attached can be dragged out from the lipid film. In order to demonstrate the formation mechanism of the lipid nanotubules produced by ultrasonic drag force clearly, a theoretical kinetic model is developed. In the experiments, the lipid nanotubules can be rapidly and efficiently fabricated using this ultrasonic transducer both in deionized water and NaCl solutions with different concentrations. The stretching speed of the lipid nanotubules can reach 33 µm/s, approximately 10 times faster than that of the existing methods. The formed lipid nanotubules have a diameter of 600 ± 100 nm (>80%). The length can reach the millimeter level. This work provided a remotely controllable, highly efficient, high-velocity, and solution environment-independent approach for fabricating lipid nanotubules.

Ultrasonic exposure parameters screening in permeability of mycobacterium smegmatis cytoderm induced by cavitation based on artificial neural network identification.

The low intensity ultrasound has been adopted by researchers to enhance the bactericidal effect against bacteria in vitro and in vivo. Although the mechanism is not completely understood, one dominant opinion is that the permeability increases because of acoustic cavitation. However, the relationship between ultrasonic exposure parameters and cavitation effects is not definitely addressed. In this paper, by establishing a modified artificial neural network (ANN) model between ultrasonic parameters and cavitation effects, the cavitation effects can be predicted and inversely the direction for choosing parameters can be given despite of different ultrasonic systems. Compared with the generic model, the computational results obtained by modified model are more close to experimental results with low calculation cost. It means that as an efficient solution, the validity of the new model has been proved. Although the research is of preliminary stage, the new method may have great value and significance because of reducing the experimental expense. The next step of this research is to explore an optimization method to obtain the most suitable parameters based on this identification model. We hope it can give a guideline for future applications in ultrasonic therapy.

A rapid and non-invasive method for measuring the peak positive pressure of HIFU fields by a laser beam.

Based on the acousto-optic interaction, we propose a laser deflection method for rapidly, non-invasively and quantitatively measuring the peak positive pressure of HIFU fields. In the characterization of HIFU fields, the effect of nonlinear propagation is considered. The relation between the laser deflection length and the peak positive pressure is derived. Then the laser deflection method is assessed by comparing it with the hydrophone method. The experimental results show that the peak positive pressure measured by laser deflection method is little higher than that obtained by the hydrophone, confirming that they are in reasonable agreement. Considering that the peak pressure measured by hydrophones is always underestimated, the laser deflection method is assumed to be more accurate than the hydrophone method due to the absence of the errors in hydrophone spatial-averaging measurement and the influence of waveform distortion on hydrophone corrections. Moreover, noting that the Lorentz formula still remains applicable to high-pressure environments, the laser deflection method exhibits a great potential for measuring HIFU field under high-pressure amplitude. Additionally, the laser deflection method provides a rapid way for measuring the peak positive pressure, without the scan time, which is required by the hydrophones.

Optimal electrode shape and size of a few singly rotated quartz and langasite resonators.

Based on Mindlin's early work, we calculate and plot optimal electrode shape and size of Y-cut quartz, At-cut quartz, and Y-cut langasite plate thickness-shear resonators. The electrodes obtained are optimal in that they satisfy Bechmann's number in every direction. The results are useful in the design optimization of these resonators.

Nonlinear coupling between thickness- shear and thickness-stretch modes in a rotated Y-cut quartz resonator.

We point out an implication of the Poynting effect in nonlinear elasticity. It is shown that, due to the Poynting effect, thickness-stretch vibration can be induced in a plate thickness-shear mode resonator of rotated Y-cut quartz when the thickness-shear deformation is no longer infinitesimal. This nonlinear coupling is particularly strong when the frequency of the thickness-stretch mode is twice the frequency of the thickness-shear mode. The induced thickness-stretch vibration affects the operating thickness-shear mode through Mathieu's equation.

Effect of mass layer stiffness on propagation of thickness-twist waves in rotated Y-cut quartz crystal plates.

We analyze the effect of mass layer stiffness on thickness-twist waves propagating in a rotated Y-cut quartz crystal plate with thin mass layers on its surfaces. An equation that determines the dispersion relation of the waves is given and is solved numerically. Quantitative results of the effect of the mass layer stiffness on wave frequencies are presented. These results are important to the understanding and design of resonators and mass sensors.

Energy trapping in power transmission through an elastic plate by finite piezoelectric transducers.

We study transmission of electric energy through an elastic plate by acoustic wave propagation and piezoelectric transducers. Our mechanics model consists of an elastic plate with finite piezoelectric patches on both sides of the plate. A theoretical analysis using the equations of elasticity and piezoelectricity is performed. Energy trapping that describes the confinement and localization of the vibration energy is examined.

Nonlinear behavior of electric power transmission through an elastic wall by acoustic waves and piezoelectric transducers.

Weakly nonlinear behavior of electric power transmission through an elastic wall by piezoelectric transducers and acoustic waves near resonance is studied based on the cubic theory of nonlinear electroelasticity. An approximate analytical solution is obtained. Output voltage is calculated and plotted. Basic nonlinear behaviors of the power transmission structure are examined. It is found that near nonlinear resonance the electrical input-output relation loses its linearity, becomes multi-valued, and experiences jumps due to large mechanical deformations. The behavior below and above resonance is qualitatively different and is qualitatively material dependent.

Vibration characteristics of a circular cylindrical panel piezoelectric transducer.

We study the theory of the basic vibration characteristics of a circular cylindrical shell piezoelectric transducer. The linear theory of piezoelectricity is used. Both the free-vibration solution for resonant frequencies and modes as well as the electrically forced-vibration solution for admittance are obtained. Numerical results are presented.

A thickness mode acoustic wave sensor for measuring interface stiffness between two elastic materials.

We studied thickness vibration of 2 elastic layers with an elastic interface mounted on a plate piezoelectric resonator. The effect of the interface elasticity on resonant frequencies was examined. The result obtained suggests an acoustic wave sensor for measuring the elastic property of an interface between 2 materials.

Membrane analogy of the Stevens-Tiersten equation for essentially thickness modes in plate quartz resonators.

We show that the well-known Stevens-Tiersten equation for essentially thickness modes in doubly rotated quartz resonators is mathematically analogous to the equation governing the transverse motion of a pre-stretched elastic membrane resting on an elastic foundation. The implication of this analogy is that commercial finite element software for structural analysis can be used to solve the Stevens-Tiersten equation for resonators.

Transmitting electric energy through a closed elastic wall by acoustic waves and piezoelectric transducers.

Transmission of electric energy through a closed elastic wall by piezoelectric transducers and acoustic waves is studied based on the linear theory of piezoelectricity and elasticity. A theoretical analysis is performed. For the structure and motion considered, the 3-D equations of linear piezoelectricity reduce to a 1-D mathematical problem. An exact solution is obtained. Transmitted voltage, current, power, efficiency and stress distribution are obtained. Their dependence on various parameters is examined. The model and results of this paper are closer to real situations compared with those in a previous analysis.

On the eigenvalue problem for free vibrations of a piezoelectric/piezomagnetic body.

We present a systematic analysis of the eigenvalue problem associated with free, small-amplitude vibrations in an elastic body possessing piezoelectric, piezomagnetic, and magnetoelectric couplings. An abstract formulation is introduced. The operators in the abstract formulation are shown to be self-adjoint, from which a series of fundamental properties of resonant frequencies and vibration modes are proved concisely. A variational formulation and a perturbation analysis of the eigenvalue problem are also given, based on the abstract formulation.