ABSTRACT
Medical imaging has relied on ultrasound (US) as an exploratory method for decades. Nonetheless, in cell biology, the numerous US applications are mainly in the research and development phase. In this review, we report the main effects on human or mammal cells of US induced by bulk or surface acoustic waves (SAW). At low frequencies, bulk US can lead to cell death. Under specific intensities and exposure times, however, cell proliferation and migration can be enhanced through cytoskeleton fluidization (a reorganization of the actin filaments and microtubules). Cavitation phenomena, frequencies of resonance close to those of the biological compounds, and mechanical transfers of energy from the acoustic pressure could explain those biological outcomes. At higher frequencies, no cavitation is observed. However, USs of high frequency stimulate ionic channels and increase cell permeability and transfection potency. Surface acoustic waves are increasingly exploited in microfluidics, especially for precise cell manipulations and cell sorting. With applications in diagnosis, infection, cancer treatment, or wound healing, US has remarkable potential. More mechanotransduction studies would be beneficial to understand the distinct roles of temperature rise, acoustic streaming and mechanical and electrical stimuli in the field.
ABSTRACT
Love wave (L-SAW) sensors have been used to probe cell monolayers, but their application to detect changes beyond the focal adhesion points on cell monolayers, as viscosity changes on the cytoskeleton, has not been explored. In this work we present for the first time a Love wave sensor with tuned penetration depth and sensitivity to potentially detect mechanical changes beyond focal adhesion points of cell monolayers. We designed and fabricated a Love wave sensor operating at 30 MHz with sensitivity to detect viscous changes between 0.89 and 3.3 cP. The Love wave sensor was modeled using an acoustic transmission line model, whereas the response of interdigital transducers (IDTs) was modeled with the Campbell's cross-field circuit model. Our design uses a substrate with a high electromechanical coupling coefficient (LiNbO3 36Y-X), and an 8-µm polymeric guiding layer (SU-8). The design aims to overcome the high insertion losses of viscous liquid environments, and the loss of sensitivity due to the low frequency. The fabricated sensor was tested in a fluidic chamber glued directly to the SU-8 guiding layer. Our experiments with liquids of viscosity similar to those expected in cell monolayers showed a measurable sensor response. In addition, experimentation with SaOs-2 cells within a culture medium showed measurable responses. These results can be of interest for the development of novel cell-based biosensors, and novel characterization tools for cell monolayers.
