Sonochemistry, although established in various fields, is still an emerging field finding new effects of ultrasound on chemical systems and are of particular interest for the biomedical field. This interdisciplinary area of research explores the use of acoustic waves with frequencies ranging from 20 kHz to 1 MHz to induce physical and chemical changes. By subjecting liquids to ultrasonic waves, sonochemistry has demonstrated the ability to accelerate reaction rates, alter chemical reaction pathways, and change physical properties of the system while operating under mild reaction conditions. It has found its way into diverse industries including food processing, pharmaceuticals, material science, and environmental remediation. This review provides an overview of the principles, advancements, and applications of sonochemistry with a particular focus on the domain of (bio-)medicine. Despite the numerous benefits sonochemistry has to offer, most of the research in the (bio-)medical field remains in the laboratory stage. Translation of these systems into clinical practice is complex as parameters used for medical ultrasound are limited and toxic side effects must be minimized in order to meet regulatory approval. However, directing attention towards the applicability of the system in clinical practice from the early stages of research holds significant potential to further amplify the role of sonochemistry in clinical applications.

Metastable polymorphic pharmaceuticals have garnered significant attention in recent years due to their enhanced physicochemical properties, including solubility, bioavailability, and intellectual property considerations. However, the manufacturing of metastable form pharmaceuticals remains a formidable challenge. The stable preparation of metastable carvedilol (CVD) form Ⅱ crystals during CVD production is elusive, leading to substantial inconsistencies in product quality and regulatory compliance. In this study, we successfully prepared metastable CVD Form Ⅱ crystals using a continuous tubular crystallizer. Our findings demonstrate that the tubular crystallizer exhibits high efficiency and robustness for generating metastable crystal Form Ⅱ. We optimized the crystallization process by incorporating air bubble segments and employing ultrasonic irradiation strategies to overcome blockages and wall sticking issues encountered during operation. Ultimately, we developed an ultrasound-assisted continuous slug-flow tubular crystallization method and evaluated its performance. The results indicate that the CVD crystals produced through this process are resilient, sustainable, and uninterrupted products with promising potential for producing metastable polymorphic pharmaceuticals while effectively addressing encrustation problems associated with continuous tubular crystallization.

The actual food system with fat is always complex and fat crystal and fat crystal networks have important effects on the physical properties of food. Recently, power ultrasound (PU) had been widely recognized as an auxiliary technology of fat crystallization to modify food properties. This review expounded on the mechanism of ultrasonic crystallization, and summarized effects of various factors in the process of ultrasonic treatment on fat crystallization. Based on the above, combined with the application of ultrasound in emulsions, the ultrasonic fat crystallization effect in the emulsion system was judged and described. Research results indicated that PU could shorten the induction time of crystallization, accelerate the formation of crystal nuclei, and change the polymorphism of fat crystals. The product treated by PU formed smaller and more uniform crystals to produce a more viscoelastic fat crystal network. In emulsion systems, ultrasonic treatments showed the same effect, but the effect of ultrasonic crystallization on the emulsion stability was different due to fat crystals in different emulsion systems. Meanwhile, the importance of ultrasonic crystallization in lipid emulsions was emphasized, thus ultrasonic crystallization had great potential in emulsion systems.

Ultrasound is known to promote crystal nucleation, but despite significant research there remains uncertainty about how the mechanisms are affected. Despite the proposal of various primary nucleation theories, most studies provide no way to quantify or observe the extent to which primary nucleation is taking place, leaving open the possibility that sonocrystallisation is occurring by a secondary nucleation-driven mechanism. By utilising the widely reported enantiomeric properties of sodium chlorate, the extent to which ultrasound can induce primary nucleation can clearly be observed. It was demonstrated during seeded cooling crystallisation that when stirring the seed similarity was 99.3% on average, indicating secondary nucleation had almost exclusively taken place. The application of ultrasound however, decreased the seed similarity to 85.8% and 92.4% when applying 98 kHz and 200 kHz ultrasound respectively, clearly showing that primary nucleation had been induced and indicating the frequency dependency of the induced primary nucleation. This frequency dependency suggests a link between crystal nucleation and high intensity cavitation collisions and collapses, and the potential existence of a collapse/collision intensity threshold required to induce primary nucleation. In addition, secondary nucleation rate was investigated using anti-solvent crystallisation and was observed to increase with the application of ultrasound, though it appeared frequency independent (between 98 kHz & 200 kHz), suggesting that higher energy cavitational events are less important in inducing secondary nucleation or that a lower cavitation intensity threshold exists compared to primary nucleation.

The preparation of micron- to nanometer-sized functional materials with well-defined shapes and packing is a key process to their applications. There are many ways to control the crystal growth of organic semiconductors. Adding polymer additives has been proven a robust strategy to optimize semiconductor crystal structure and the corresponding optoelectronic properties. We have found that poly(3-hexylthiophene) (P3HT) can effectively regulate the crystallization behavior of N,N\'-dioctyl perylene diimide (C8PDI). In this study, we combined P3HT and polyethylene glycol (PEG) to amphiphilic block copolymers and studied the crystallization modification effect of these block copolymers. It is found that the crystallization modification effect of the block copolymers is retained and gradually enhanced with P3HT content. The length of C8PDI crystals were well controlled from 2 to 0.4 μm, and the width from 210 to 35 nm. On the other hand, due to the water solubility of PEG block, crystalline PEG-b-P3HT/C8PDI micelles in water were successfully prepared, and this water phase colloid could be stable for more than 2 weeks, which provides a new way to prepare pollution-free aqueous organic semiconductor inks for printing electronic devices.

High-intensity ultrasound (HIU) has been used in the past to change fat crystallization and physical properties of fat crystalline networks. The objective of this work was to evaluate how HIU placed on different positions in a scraped surface heat exchanger (SSHE) using different processing conditions affect the physical properties of an interesterified palm olein. The sample was crystallized at two temperatures (20 °C and 25 °C) and two agitation rates (344/208 rpm and 185/71 rpm, barrels/pin worker). HIU (12.7 mm-diameter tip, 50% amplitude, 5 s pulses) was placed at three different positions within the SSHE. After processing, samples were stored at 25 °C for 48 h and analyzed according to the crystal morphology, solid fat content (SFC), oil binding capacity (OBC), melting behavior, viscoelasticity, and hardness. Physical properties were affected by crystallization conditions, by sonication, and by HIU position. The greatest improvement obtained was at 20 °C using low agitation when HIU was placed at the beginning of the SSHE. These conditions result in a sample with 98.9% of OBC, 274 kPa of viscoelasticity and 31 N of hardness. These results show that HIU can be used as an additional processing tool to improve physical properties of a palm-based fat and that the best improvement was obtained as a combination of crystallization conditions and HIU position.

Ultrasonication to supersaturated protein solutions forcibly forms amyloid fibrils, thereby allowing the early-stage diagnosis for amyloidoses. Previously, we constructed a high-throughput sonoreactor to investigate features of the amyloid-fibril nucleation. Although the instrument substantiated the ultrasonication efficacy, several challenges remain; the key is the precise control of the acoustic field in the reactor, which directly affects the fibril-formation reaction. In the present study, we develop the optimized sonoreactor for the amyloid-fibril assay, which improves the reproducibility and controllability of the fibril formation. Using β2-microglobulin, we experimentally demonstrate that achieving identical acoustic conditions by controlling oscillation amplitude and frequency of each transducer results in identical fibril-formation behavior across 36 solutions. Moreover, we succeed in detecting the 100-fM seeds using the developed sonoreactor at an accelerated rate. Finally, we reveal that the acceleration of the fibril-formation reaction with the seeds is achieved by enhancing the primary nucleation and the fibril fragmentation through the analysis of the fibril-formation kinetics. These results demonstrate the efficacy of the developed sonoreactor for the diagnosis of amyloidoses owing to the accelerative seed detection and the possibility for further early-stage diagnosis even without seeds through the accelerated primary nucleation.

Due to the high reactivity of Ag+ and uncontrolled growth process, the AgNPs produced by conventional Lee-Meisel method always exhibited larger particle size (30-200 nm) and polydisperse morphology (including spherical, triangular, and rod-like shape). An ultrasound-intensified Lee-Meisel (UILM) method is developed in this study to environmental-friendly and controllable synthesize monodisperse spherical AgNPs (~3.7 nm). Effects of Ag:citrate ratio (1:3 or 5:4), ultrasound power (300 to 1200 W) and reaction time (4 to 24 min) on the physical-chemical properties of AgNPs are investigated systematically. The transmission electron microscope (TEM) images, UV-Vis spectra, average particle size, zeta potential and pH value all demonstrate that crystallization and digestive ripening processes are facilitated in the presence of ultrasound irradiation. Therefore, both chemical reaction rate and mass transfer rate are enhanced to accelerate primary nucleation and inhibit uncontrolled particle growth, leading to the formation of monodisperse spherical AgNPs. Moreover, a machine learning approach - Decision Tree Regressor in conjunction with Shapley value analysis reveal the concentration of reactants is a more important feature affecting the particle.

In this work, the composition of different types of chocolate was studied by using microscopy (optical and confocal fluorescence) and vibrational spectroscopy (Raman) aimed at obtaining more chemical information about this important food. By combining these techniques, it is possible to distinguish different components of chocolate. It was not possible to obtain Raman spectra of dark chocolate due to the presence of fluorescent flavonoids in cocoa particles. However, silver nanoparticles quench this fluorescent signal, and thus it is possible to obtain a surface-enhanced Raman spectroscopy spectrum of dark chocolate. The effect of ultrasound on the crystallization process of cocoa butter was also studied. These samples were also analysed by X-ray diffraction and differential scanning calorimetry. Furthermore, the combination of all these techniques was very useful in the specific analysis of different components of chocolate and could have a high impact in the chocolate industry.

The objective of this work was to evaluate the effect that agitation rate, crystallization temperature, and sonication have on the physical properties of a soybean-based fat with low levels of saturated fatty acids crystallized in a scraped surface heat exchanger (SSHE). The sample was crystallized at two temperatures (20 and 25 °C) and agitation rates (344/208 rpm in the barrels/pin worker-high agitation HA and 185/71 rpm barrels/pin worker-low agitation LA), and a constant flow of 11 L/hr. High-intensity ultrasound (HIU - 12.7 mm-diameter tip, 50% amplitude, 5 s pulses) was coupled to a water jacketed flow-cell and placed at three different positions within the SSHE. The combination of all those parameters affected samples\' physical properties. Higher oil binding capacity (OBC) and elasticity (G\') were obtained at 20 °C compared to 25 °C (77% vs. 63.78% for OBC and 30.4 kPa vs. 6 kPa for G\', respectively) due to the smaller crystals formed at 20 °C. Fewer or no differences were observed due to agitation alone, but LA conditions allowed for more secondary nucleation to form due to sonication and resulted in a higher improvement on the properties of the fat. PRACTICAL APPLICATION: Fat crystallization in a scrapped surface heat exchanger (SSHE) combined with a high-intensity ultrasound (HIU) gives a realistic idea of how the HIU would work in an industrial line under continuous flow, shaved shear, and different supercooling. Results from this research will provide industry with tools on how and where to incorporate HIU in their processing line. Moreover, will give information on how to combined crystallization conditions and sonocrystallization in order to obtain improved physical properties.