Micron sized, lipid stabilized bubbles of gas are of interest as contrast agents for ultra-sound (US) imaging and increasingly as delivery vehicles for targeted, triggered, therapeutic delivery. Microfluidics provides a reproducible means for microbubble production and surface functionalisation. In this study, microbubbles are generated on chip using flow-focussing microfluidic devices that combine streams of gas and liquid through a nozzle a few microns wide and then subjecting the two phases to a downstream pressure drop. While microfluidics has successfully demonstrated the generation of monodisperse bubble populations, these approaches inherently produce low bubble counts. We introduce a new micro-spray flow regime that generates consistently high bubble concentrations that are more clinically relevant compared to traditional monodisperse bubble populations. Final bubble concentrations produced by the micro-spray regime were up to 10(10) bubbles mL(-1). The technique is shown to be highly reproducible and by using multiplexed chip arrays, the time taken to produce one millilitre of sample containing 10(10) bubbles mL(-1) was ∼10 min. Further, we also demonstrate that it is possible to attach liposomes, loaded with quantum dots (QDs) or fluorescein, in a single step during MBs formation.

structures which exhibit extraordinary behaviour(s). This review represents a comprehensive account of the state-of-the-art in the production of such metamaterials using additive manufacturing methods and highlights areas, which, based on trends observed in the literature, are worthy of further research and require a coordinated effort on behalf of the afore mentioned disciplines in order to advance the state-of-the-art.

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Important aspects in engineering gold nanoparticles for theranostic applications include the control of size, optical properties, cytotoxicity, biodistribution and clearance. In this study,

Open platform (OP) ultrasound systems are aimed primarily at the research community. They have been at the forefront of the development of synthetic aperture, plane wave, shear wave elastography, and vector flow imaging. Such platforms are driven by a need for broad flexibility of parameters that are normally preset or fixed within clinical scanners. OP ultrasound scanners are defined to have three key features including customization of the transmit waveform, access to the prebeamformed receive data, and the ability to implement real-time imaging. In this paper, a formative discussion is given on the development of OPs from both the research community and the commercial sector. Both software- and hardware-based architectures are considered, and their specifications are compared in terms of resources and programmability. Software-based platforms capable of real-time beamforming generally make use of scalable graphics processing unit architectures, whereas a common feature of hardware-based platforms is the use of field-programmable gate array and digital signal processor devices to provide additional on-board processing capacity. OPs with extended number of channels (>256) are also discussed in relation to their role in supporting 3-D imaging technique development. With the increasing maturity of OP ultrasound scanners, the pace of advancement in ultrasound imaging algorithms is poised to be accelerated.

Abstract-Linear frequency modulated (LFM) excitation combined with pulse compression provides an increase in signal to noise ratio (SNR) at the receiver. LFM signals are of longer duration than pulsed signals of the same bandwidth. Consequently, in many practical situations, maintaining temporal separation between echoes is not possible. Where analysis is performed on individual LFM signals, a separation technique is required. Time windowing is unable to separate signals overlapping in time. Frequency domain filtering is unable to separate signals with overlapping spectra. This paper describes a method to separate time overlapping LFM signals through the application of the fractional Fourier transform (FrFT), a transform operating in both time and frequency domains. A short introduction to the FrFT, its operation and calculation are presented. The proposed signal separation method is illustrated by application to a simulated ultrasound signal, created by the summation of multiple time overlapping LFM signals and the component signals recovered with ±0.6% spectral error. The results of an experimental investigation are presented where the proposed separation method is applied to time overlapping LFM signals, created by the transmission of a LFM signal through a stainless steel plate and water-filled pipe.

Micron-sized lipid-stabilised bubbles of heavy gas have been utilised as contrast agents for diagnostic ultrasound (US) imaging for many years. Typically bubbles between 1 and 8 μm in diameter are produced to enhance imaging in US by scattering sound waves more efficiently than surrounding tissue. A potential area of interest for Contrast Enhanced Ultrasound (CEUS) are bubbles with diameters <1 μm or 'nanobubbles.' As bubble diameter decreases, ultrasonic resonant frequency increases, which could lead to an improvement in resolution for high-frequency imaging applications when using nanobubbles. In addition, current US contrast agents are limited by their size to the vasculature in vivo. However, molecular-targeted nanobubbles could penetrate into the extra-vascular space of cancerous tissue providing contrast in regions inaccessible to traditional microbubbles. This paper reports a new microfluidic method for the generation of sub-micron sized lipid stabilised particles containing perfluorocarbon (PFC). The nanoparticles are produced in a unique atomisation-like flow regime at high production rates, in excess of 10(6) particles per s and at high concentration, typically >10(11) particles per mL. The average particle diameter appears to be around 100-200 nm. These particles, suspected of being a mix of liquid and gaseous C4F10 due to Laplace pressure, then phase convert into nanometer sized bubbles on the application of US. In vitro ultrasound characterisation from these nanoparticle populations showed strong backscattering compared to aqueous filled liposomes of a similar size. The nanoparticles were stable upon injection and gave excellent contrast enhancement when used for in vivo imaging, compared to microbubbles with an equivalent shell composition.

This paper investigates the characteristics of the shadowed fading observed in off-body communications channels at 5.8 GHz. This is realized with the aid of the κ-μ/gamma composite fading model, which assumes that the transmitted signal undergoes κ-μ fading, which is subject to multiplicative shadowing. Based on this, the total power of the multipath components, including both the dominant and scattered components, is subject to non-negligible variations that follow the gamma distribution. For this model, we present an integral form of the probability density function (PDF) as well as important analytic expressions for the PDF, cumulative distribution function, moments, and moment generating function. In the case of indoor off-body communications, the corresponding measurements were carried out in the context of four explicit individual scenarios, namely: line of sight (LOS), non-LOS walking, rotational, and random movements. The measurements were repeated within three different indoor environments and considered three different hypothetical body worn node locations. With the aid of these results, the parameters for the κ-μ/gamma composite fading model were estimated and analyzed extensively. Interestingly, for the majority of the indoor environments and movement scenarios, the parameter estimates suggested that dominant signal components existed even when the direct signal path was obscured by the test subject's body. In addition, it is shown that the κ-μ/gamma composite fading model provides an adequate fit to the fading effects involved in off-body communications channels. Using the Kullback-Leibler divergence, we have also compared our results