Based on the Church-Hoff model, the nonlinear oscillations of a single encapsulated microbubble with a finite thickness shell are theoretically studied. The effects of viscoelasticity on radial oscillations and the fundamental and harmonic components are researched. The peaks of radial oscillations and magnitudes of power spectra of the fundamental and harmonic components all increase gradually with the shear modulus of shell varying from 0 to 10 MPa by an interval of 0. 1 MPa at the same shear viscosity, while they decrease as the shear viscosity increases from 0 to 1 Pa · s by an interval of 0. 01 Pa · s at the same shear modulus. The fluctuation ranges of subharmonic and ultraharmonic signals are much larger than both the fundamental and second harmonic components. It means that the effect of viscoelasticity on the subharmonic and ultraharmonic signals is greater than that on the fundamental and second harmonic components. So adjusting the viscoelasticity of the shell is a potential method to obtain a perfect microbubble contrast agent used for the subharmonic and ultraharmonic imaging. Four points with significant fundamental and harmonic components are chosen as an example: a shear viscosity of 0. 39 Pa · s with shear modulus of 3.9, 6. 6, and 8.6 MPa, respectively; a shear modulus of 6.6 MPa with a shear viscosity of 0.42 Pa · s.
A system for in vitro investigation of ultrasound contrast agent's enhancement effect is presented and evaluated. It includes the digital B-mode ultrasound scanner Belson3000A, the tissue-mimicking ultrasound phantoms and the software which is used for image quantitative analysis. The linear range, optimal settings and repeatability of the system are assessed and explored by scanning the ultrasound phantoms with different reflective intensities. The measurements are performed under an acoustic power from 4.8 to 12.3 mW, the scanner centre frequency is 3.5 MH and the gain setting is 50 dB. Both a self-made surfactant encapsulated microbubble and a commercial ultrasound contrast agent are scanned. The results show that the pixel intensity of ultrasonic images increases with the increase in the sound power, and for the stronger reflective phantoms of more particles, the increasing trend is much more evident. The system is optimal for evaluating the microbubble contrast agents' enhancement effects. It presents a simple, effective and real-time means for characterizing the enhancement ability of microbubbles.
With the rapid development of nanotechnology and increasingly broad bio-application of engineered nanomaterials, their bio- hazards have become a serious public concern. It is believed that the chemical nature, particle size, morphology, and surface chemistry of nanomaterials are key parameters that influence their toxicity. Although cultured ceils have been widely used to evaluate nanomaterial toxicity, it remains unclear whether the passage of these cells affects the evaluation results. In the pre- sent study, Ba/F3 cells transfected with the BCR-ABL gene were subcultured to study the effect of passage number on cell sta- bility and their cellular responses upon exposure to nanomaterials. The results demonstrated that proliferation, cellular senes- cence, BCR-ABL gene expression, cell cycle and apoptosis were stable across multiple passages. Senescence and BCR-ABL gene expression of cells from different passage cells were unchanged when treated with silver nanoparticles (AgNPs). In addi- tion, the cells at multiple passage numbers were all arrested in the G2/M phase and apoptosis was induced by the AgNPs. These nanoparticles could enter cells via endocytosis and localize in the cndosomes, which were also not influenced by passage number. These data suggest that short-term passage would not affect cultured cell stability and toxicity assessment using these cells would be consistent when maintained appropriately.
GUO DaWeiZHANG XiuYanHUANG ZhiHaiZHOU XueFengZHU LingYingZHAO YunGU Ning
Encapsulated gas microbubbles are well known as ultrasound contrast agents (UCAs) for medical ultrasound (US) imaging. With the development of shell materials and preparation technologies, the application of microbubbles has been enormously popular in molecular imaging, drug delivery and targeted therapy, etc. The objective of this study is to develop Fe3O4 nanoparticle-inclusion microbubble construct. The in vitro US imaging experiment indicates that the Fe3O4 nanoparticle-inclusion microbubbles have higher US enhancement than those without Fe3O4 nanoparticle-inclusion. According to the microbubble dynamic theory, the acoustic scattering properties can be quantified by scattering cross-section of the shell. The scattering study on Fe3O4 nanoparticle-inclusion microbubbles of different concentration shows that within a certain range of concentration, the scattering cross-section of microbubble increases with the addition of Fe3O4 nanoparticles. When exceeding the concentration range, the ultrasonic characteristic of microbubbles is damped. On the other hand, since Fe3O4 nanoparticles can also serve as the Magnetic Resonance Imaging (MRI) contrast agent, they can be potentially used as contrast agents for the double-modality (MRI and US) clinical studies. However, it is important to control the concentration of Fe3O4 nanoparticles in the shell in order to realize the combined functions of US and MRI.
The development of nanobiology requires a fundamental understanding of the interaction features between light and cells as well as cells containing nanoparticles. In this study, the generalized multiparticle Mie (GMM) theory was employed to calculate the scattering properties of cells under refractive index matching conditions. The angular distribution of scattered light is statistically averaged to obtain a good fit for the experimental results. Based on a simplified cell model, the variabilities between the scattered light pattern of normal cells and that of cancerous cells were examined. The results indicate that the small angle scattering is sensitive to the organelle distribution, which could be applied in the diagnostics of cancerous cells. Finally, the effects of cellular uptake of nanoparticles on the scattering pattern was also investigated.