Sono-crystallisation has been used to enhance crystalline product quality particularly in terms of purity, particle size and size distribution. In this work, the effect of impurities and ultrasound on crystallisation processes (nucleation temperature, yield) and crystal properties (crystal size distribution determined by Focused Beam Reflectance Measurement (FBRM), crystal habit, filtration rate and impurity content in the crystal product by Liquid Chromatography-Mass Spectroscopy (LC-MS)) were investigated in bulk suspension crystallisation experiments with and without the use of ultrasound. The results demonstrate that ultrasonic intervention has a significant effect on both crystallisation and product crystal properties. It increases the nucleation rate resulting in smaller particles and a narrower Particle Size Distribution (PSD), the yield has been shown to be increase as has the product purity. The effect of ultrasound is to reduce the level acetanilide impurity incorporated during growth from a 2 mol% solution of the selected impurity from 0.85 mol% to 0.35 mol% and likewise ultrasound reduces the uptake of metacetamol from 1.88 mol% to 1.52 mol%.

Wider operational bandwidth is an important requirement of an ultrasound transducer across many applications. In nature, it can be observed that several hearing organs possess a broad operating bandwidth by having a varying length scales structure. Moreover, conventional 1-3 piezoelectric composite transducers have been widely recognized for their wider bandwidth over their piezoelectric ceramic counterparts. In this paper, a novel 1-3 piezoelectric composite design using a fractal geometry, known as the Sierpinski Gasket (SG), is proposed in order to explore the potential of further extending the operational bandwidth and sensitivity of the transducer. Two equivalent 1-3 piezocomposite designs are compared to this end, one with a conventional periodic parallelepiped shaped pillar structure and one with the SG fractal geometry, both theoretically, using a finite element (FE) analysis package, and experimentally. The transmit voltage response and open circuit voltage response are used to illustrate bandwidth improvement from the fractal composite design. Following the simulation results, a 580 kHz single element transducer, utilizing the proposed SG fractal microstructure, is fabricated using a pillar placement methodology. The performance of the prototyped device is characterized and compared with a conventional 1-3 composite design, as well as with a commercial ultrasound transducer. In the one-way transmission mode, a bandwidth improvement of 27.2 % and sensitivity enhancement of 3.8 dB can be found with the SG fractal design compared to an equivalent conventional composite design and up 105.1 % bandwidth improvement when compared to the commercial transducer. In the one-way reception mode, the bandwidth improvement for the SG fractal design is 2.5 % and 32.9 % when compared to the conventional and commercial transducers, respectively.

Systemically circulating microbubbles are used as contrast agents to aid both drug targeting and delivery using ultrasound. Exploiting their acoustic behaviour in small diameter vessels is critical for both applications, but the highly controlled experiments required to support this are not possible in vivo and challenging in vitro. Experimental platforms with small diameter channels (below 200 microns) are not readily available nor able to represent vascular geometries, leaving the existence and extent of microbubble-microvessel interactions incompletely defined. In this work we present a 3D-printed microchannel platform using tissue-mimicking hydrogels featuring radii down to 75 microns. We demonstrate application to study microbubble behaviour via acoustic backscatter under controlled environments in physiologically-relevant conditions.

We have previously demonstrated product purity enhancement during the crystallization of paracetamol in a low intensity ultrasound field. In order to elucidate the underlying mechanisms of sonocrystallization, the applied ultrasonic interventions were characterized by measurements of cavitation bubble number, size and size distribution with a Mettler FBRM probe. Ultrasonic intensity measurements were conducted using a needle hydrophone. The solvents selected for study; water, ethanol and isoamyl alcohol show significant differences in behavior. This data provides an insight into the relationship between solvent properties and cavitation bubble activity under the same applied ultrasonic energy. Substantially more cavitation bubbles form in the organic solvents compared with water, this is consistent with the lower surface tension and higher vapor pressure of the organic solvents. The difference in bubble size distributions between ethanol and isoamyl alcohol is significant. In ethanol most bubbles remain below 30μm whereas in isoamyl alcohol they tend towards 1mm in size. Detection, quantification and measurement of cavitation bubbles in crystallization solvents contributes further evidence that acoustic cavitation is a key component in sonocrystallization. The industrial driver is to incorporate this understanding into both pharmaceutical process and equipment design to improve the product quality, reduce waste and improve access to medicines.