Today, surface acoustic waves (SAWs) and bulk acoustic waves are already two of the very few phononic technologies of industrial relevance and can been found in a myriad of devices employing these nanoscale earthquakes on a chip. Acoustic radio frequency filters, for instance, are integral parts of wireless devices. SAWs in particular find applications in life sciences and microfluidics for sensing and mixing of tiny amounts of liquids. In addition to this continuously growing number of applications, SAWs are ideally suited to probe and control elementary excitations in condensed matter at the limit of single quantum excitations. Even collective excitations, classical or quantum are nowadays coherently interfaced by SAWs. This wide, highly diverse, interdisciplinary and continuously expanding spectrum literally unites advanced sensing and manipulation applications. Remarkably, SAW technology is inherently multiscale and spans from single atomic or nanoscopic units up even to the millimeter scale. The aim of this Roadmap is to present a snapshot of the present state of surface acoustic wave science and technology in 2019 and provide an opinion on the challenges and opportunities that the future holds from a group of renown experts, covering the interdisciplinary key areas, ranging from fundamental quantum effects to practical applications of acoustic devices in life science.

Fifteen years ago, surface acoustic waves (SAW) were found to be able to drive fluids and numerous applications in microfluidics have been developed since. Here, we review the progress made and report on new approaches in setting-up microfluidic, continuous flow acoustic mixing. In a microchannel, chaotic advection is achieved by generation of a SAW driven fluid jet perpendicular to the mean flow direction. Using a high speed video camera and particle image velocimetry, we measure the flow velocities and show that mixing is achieved in a particularly controllable and fast way. The mixing quality is determined as a function of system parameters: SAW power, volume flux and fluid viscosity. Exploring the parameter space of mixing provides a practical guide for acoustic mixing in microchannels and allows for adopting conditions to different solvents, as e.g., required for the generation of nanoscale particles from alcoholic phases. We exemplarily demonstrate the potential of SAW based continuous flow mixing for the production of therapeutic nucleic acid nanoparticles assembled from polymer and lipid solutions.

A novel, ultrasound based approach for the dynamic stimulation and promotion of tissue healing processes employing surface acoustic waves (SAW) on a chip is presented for the example of osteoblast-like SaOs-2 cells. In our investigations, we directly irradiate cells with SAW on a SiO₂ covered piezoelectric LiNbO₃ substrate. Observing the temporal evolution of cell growth and migration and comparing non-irradiated to irradiated areas on the chip, we find that the SAW–treated cells exhibit a significantly increased migration as compared to the control samples. Apart from quantifying our experimental findings on the cell migration stimulation, we also demonstrate the full bio compatibility and bio functionality of our SAW technique by using LDH assays. We safely exclude parasitic side effects such as a SAW related increased substrate temperature or nutrient flow by thoroughly monitoring the temperature and the flow field using infrared microscopy and micro particle image velocimetry. Our results show that the SAW induced dynamic mechanical and electrical stimulation obviously directly promotes the cell growth. We conclude that this stimulation method offers a powerful platform for future medical treatment, e.g. being implemented as a implantable biochip with wireless extra-corporal power supply to treat deeper tissue.

Significance: Ultrasonic pressure fields have been proven to be beneficial for cell growth in vitro and in patients. However, conventional therapeutic-ultrasound treatment is subjected to limitations such as time restriction, external application, or energy loss. The application of surface acoustic waves (SAWs) can help to overcome some drawbacks. To understand the underlying mechanism, the adjusting parameters of SAWs and the intracellular response to the stimulation are evaluated. We identified a dependence of cell growth on SAW intensity and the presence of a vertical substrate deflection. While the cellular stress (reactive oxygen species) remains in the normal range, both cell migration and proliferation are increased. Due to the experimental design, the effect of enhanced cell growth is dominated by increased cell migration.

Automated mixing of fluids with control over mixing parameters is of highest importance for reproducible production and chemical synthesis processes. We here introduce surface acoustic waves (SAW) induced mixing of µ l droplets for tailorable nanoparticle (NP) formation. Nucleic acid therapeutics represent extremely potent and innovative approaches to a variety of medical challenges, such as the treatment of cancer and genetic diseases. In this study, we apply this method to produce nucleic acid polymer complexes. Fusing two droplets containing either pDNA or cationic polymers leads to the formation of well-defined polyplexes. We show that droplet size and incubation time do not influence the desired particle characteristics significantly. However, the resulting nanoparticle diameter strongly depends on the SAW power level and educt concentrations, which indicates a kinetically controlled assembly process, while the particle shape is largely unaffected. Applying our novel technique to the formation of three-component-NP, we find that the choice of the mixing order can be used to decrease NP size even further. To address the kinetic interplay between mixing and particle growth, we apply our technique to homogenous mixing at high salt concentrations followed by a subsequent dilution step. Finally, by comparing various hand and SAW mixed polyplexes, we demonstrate significant differences in size while the cytotoxicity and in vitro efficacy remain roughly the same.