Ketan Pancholi

Increasing the nonlinear character of microbubble oscillations at low acoustic pressures

The nonlinear response of gas bubbles to acoustic excitation is an important phenomenon in both the biomedical and engineering sciences. In medical ultrasound imaging, for example, microbubbles are used as contrast agents on account of their ability to scatter ultrasound nonlinearly. Increasing the degree of nonlinearity, however, normally requires an increase in the amplitude of excitation, which may also result in violent behaviour such as inertial cavitation and bubble fragmentation. These effects may be highly undesirable, particularly in biomedical applications, and the aim of this work was to investigate alternative means of enhancing nonlinear behaviour. In this preliminary report, it is shown through theoretical simulation and experimental verification that depositing nanoparticles on the surface of a bubble increases the nonlinear character of its response significantly at low excitation amplitudes. This is due to the fact that close packing of the nanoparticles restricts bubble compression.

Dynamics of Bubble Formation in Highly Viscous Liquids

There has recently been considerable interest in the development of devices for the preparation of monodisperse microbubble suspensions for use as ultrasound contrast agents and drug delivery vehicles. These applications require not only a high degree of bubble uniformity but also a maximum bubble size of 8 mum, and this provides a strong motivation for developing an improved understanding of the process of bubble formation in a given device. The aim of this work was to investigate bubble formation in a T-junction device and determine the influence of the different processing parameters upon bubble size, in particular, liquid viscosity. Images of air bubble formation in a specially designed T-junction were recorded using a high-speed camera for different ratios of liquid to gas flow rate (Ql/Qg) and different liquid viscosities (microl). It was found that theoretical predictions of the flow profile in the focal region based on analysis of axisymmetric Stokes flow were accurate to within 6% when compared with the experimental data, indicating that this provided a suitable means of describing the bubble formation process. Both the theoretical and experimental results showed that Ql/Qg and mul had a significant influence upon bubble formation and eventual size, with higher flow rates and higher viscosities producing smaller bubbles. There were, however, found to be limiting values of Ql/Qg and mul beyond which no further reduction in bubble size was achieved.

Generation of microbubbles for diagnostic and therapeutic applications using a novel device

Developments in both diagnostic and therapeutic applications of microbubbles have greatly increased the need for more advanced preparation technologies which provide a well-defined, narrow microbubble size-distribution. In this paper, we demonstrate the use of a new device, consisting of a T-junction whose outlet capillary is fitted with an electrohydrodynamic spraying arrangement, to prepare phospholipid-coated air microbubbles, making significant advances in controlling and decreasing the size and size-distribution, and increasing the stability/lifetime of the bubbles prepared. The microbubbles were characterised via optical microscopy to determine the relationship between the size-distribution obtained and the process variables, specifically the flow rates of the phospholipid suspension and air (Ql and Qg), and the applied voltage (V). The formation of microbubbles in the device was also studied using high-speed photography. For the range of parameters investigated, the bubble diameter was found to scale with the product of the flow rate ratio (Ql/Qg) and the applied voltage, with a consistent bubble diameter of 5.1 ± 2 μm being obtained at Ql/Qg = 1.7 and V = 18 kV. The bubbles prepared using this method were found to be stable for at least 2 h at ambient temperature and pressure.

In vitro method to characterize diffusion of dye from polymeric particles: a model for drug release.

The release profile of a drug delivery system is a key factor in determining its efficacy. In the case of a polymeric particle based system, the release profile is a function of several parameters including particle diameter and porosity. The effects of these parameters are usually investigated experimentally using UV-spectroscopy. Predicting the drug release profile from particles as a result of the interaction of many parameters is desirable in order to facilitate the design of more efficient drug delivery particles. In this work, a quantitative method of determining the diffusion profile is developed which removes the need for repetitive experimentation. Particles of polymethylsilsesquioxane were prepared using coaxial electrohydrodynamic atomization and collected in solutions containing different concentrations of Evans blue dye (6, 0.6, and 0.06 mg/mL) which was used to simulate a drug. The dye release profile was calculated by solving the unsteady state diffusion equation for parameters used in the experiments. It was demonstrated that the dye release profile from particles with diameters ranging from 400 nm to 9 mum can be calculated using a simple equation without addition of a dissolution term, if the volume ratio of surrounding liquid to particle in the unsteady second order solution is substituted by the surface area of particles to liquid volume ratio. The calculated data are found to be in good agreement with the experimental, indicating that this method can be used to determine the diffusion coefficient as a function of particle diameter and material. This study represents a crucial step toward developing a full drug release model.

A review of imaging methods for measuring drug release at nanometre scale: a case for drug delivery systems

Introduction: Current drug delivery research is focused on improving the efficacy of drug delivery systems, with emphasis on precise targeting, accurate dose delivery, strategies for overcoming the tissue barrier and monitoring the effects of drugs on their targets. To realize these goals, it is essential to determine the spatio-temporal bio-distribution of particles in the whole animal. Enabling such a measurement at the nanometer scale helps in the design of efficient systems. Areas covered: This article discusses the need for molecular imaging in drug delivery development and also reviews promising imaging methods. Moreover, the physics behind each method is explained and evaluated to derive advantages and limitations. The review enables the readers to select, use and modify the existing methods to implement imaging protocols for studying drug release from particular drug delivery. Expert opinion: Currently, the difference in pharmacodynamics obtained via various imaging modalities cannot be verified and hinders clinical use. To establish imaging as a scientific tool, its translation into clinical use is vital. Presently, there is no single imaging method suitable for drug-release studies. However, hybrid imaging has the potential to provide the desired imaging system.

High yielding microbubble production method

Microfluidic approaches to microbubble production are generally disadvantaged by low yield and high susceptibility to (micro)channel blockages. This paper presents an alternative method of producing microbubbles of 2.6 μm mean diameter at concentrations in excess of 30 × 106 mL−1. In this method, the nitrogen gas flowing inside the liquid jet is disintegrated into spray of microbubble when air surrounding this coflowing nitrogen gas-liquid jet passes through a 100 μm orifice at high velocity. Resulting microbubble foam has the polydispersity index of 16%. Moreover, a ratio of mean microbubble diameter to channel width ratio was found to be less than 0.025, which substantially alleviates the occurrence of blockages during production.

In Situ Investigation of Microstructural Changes in Thermoplastic Composite Pipe Under Compressive Load

Thermoplastic composite materials are very advantageous as component layers in subsea risers due to their inherent properties such as high strength, low density, fatigue and chemical resistance. However, response of composite materials to applied loading is complex and three-dimensional in nature. The heterogeneous structure of the composite material induces irregular distribution of stress/strain over the cross-section and thus, it is essential for design to use analytical methods capable of determining the stress-strain relationship in three-dimensional space. Currently, most methods rely upon one-dimensional or two-dimensional data collection techniques with macro scale stress / strain observations for experimental validation. In order to ascertain the correct load to the failure, a complete understanding of the material failure at the micro-scale is essential.In this work, X-ray computed tomography is employed for the in situ observation of micromechanical failure of the composite material under a compressive load. The observed results are compared and validated with the traditional stress-strain data and finite element analysis. It is observed that the damage in the composite material initiates by delamination which grows as the loading progresses. Moreover, the properties and failure modes are highly dependent on the manufacturing process. By gaining further understanding of the failure modes using these methods, the findings can be utilized in optimizing the design of composite riser structures.© 2014 ASME

In Situ and Real Time X-Ray Computed Tomography for the Micromechanics Based Constitutive Modelling of the Unbonded Flexible Riser

The failure mechanism of the composite flexible riser, comprising a pipe with melt fused carbon fiber tape or pultruded composite rods, is not well understood. As there is change in the configuration of the composite layers and its manufacturing methods, so the bulk material property also changes significantly. To capture the correct material model for global FE analysis, real time x-ray computed tomography was performed while the flexible pipe was being compressed. For developing a constitutive model for the composites, a time series of 3D volume images were analyzed quantifying the local strains responsible for the debonding of the layers and the crack development. These values were then used to understand the inter-layer adhesion leading to correlation between the FE global modelling and experiments capable of capturing the progressive delamination. The resulting global modelling was used to determine the area under compressive loading. The effect of global sea conditions and cumulative damage was noted. A correlation between the global model and experiments can be used to optimize riser performance. This method hopes to capture the overall behavior of flexible pipe under compressive loading.Copyright

Integrated self-healing of the composite offshore structures

The self-repairing composite materials integrated with sensing is way forward to reduce maintenance cost and increase consumer safety. In this work, the novel self-healing carbon fibre reinforced unidirectional bulk tape of simple architecture is prepared using nanocomposite film. The bulk material tape was prepared using nanocomposite film of low melting temperature polymer sandwiched between two carbon fibre reinforced unidirectional tapes. First, the nanocomposite polyamide 6 (PA 6) tape with iron oxide nanoparticle was prepared using in-situ polymerization and mixing method. The iron oxide nanoparticle was silane coated suing tri-phasic reverse emulsion method to achieve better dispersion in PA 6 matrix. The nanocomposite was characterized using FTIR, XRD, DSC and TEM. Result shows that the proposed method of preparing self-healing bulk tape material has potential to be used for self-healing composite structure.

Insulating polymer nanocomposites for high thermal conduction and fire retarding applications.

The possibility of combining the flexibility and light - weight of polymers with the highest insulation of ceramics, drives the field of nanocomposites for potential commercial application. The inclusion of nano-sized insulating particles in the polymer matrix, and orienting the fillers along the direction of heat flow results in modifying the induced interfaces for effective phonon propagation. Such flexible polymer nanocomposites (PNC) offer easy workability and refined insulating effect with high thermal conductivity and fire-retardancy. Hence, opening a wider arena of applications with the advantage of their light-weight. The engineering of the interfaces, is the key for dictating the desired properties at the macro-scale. Consequently, silane functionalisation of nanoparticles with designed dispersion technique was tried for achieving this purpose. Transmission electron microscopy (TEM), Fourier transform infrared (FT-IR) spectroscopy, Differential scanning calorimetry (DSC), Thermogravimetric analysis (TGA), and Dynamic mechanical analysis (DMA) were done to characterize the properties and structure of the synthesised nanocomposite. This paper reports that surface modification of the nanoparticles can effectively solve the dispersion problem and reduces the electric field charge concentration at the interface. Synthesising PNC with selective nanoparticle loading percentage can yield a lmost 6-12% increase in the thermal capacity and fire retardability of the base polymer. Presenting an effective way of resulting in a commercially promising PNC suitable for various defence applications of radome technology, energy storage (e.g. batteries), structural bodies and cables in general.