A transparent ultrasound on-chip platform enables high-throughput cell stimulation and simultaneous high-resolution optical imaging

We report a novel transparent ultrasound transducer (TUT) platform for low intensity pulsed ultrasound (LIPUS) stimulation of cells and simultaneously imaging live cell fluorescent calcium dynamics using time lapse microscopy. By culturing cells directly on the biocompatible TUT surface, this platform eliminated the need for additional acoustic coupling and reduced the risk of contamination. High light transmission (> 80%) and compact size of TUTs allowed easy integration with state-of-the-art microscopy for high-resolution imaging of cells in both bright and fluorescent modes while stimulating with optimal LIPUS stimulation conditions. Quantitative single cell fluorescence analysis results demonstrated that the proposed TUT allows uniform and high-throughput stimulation of all plated cells. Dead cell assay results confirmed cell viability after LIPUS. In the future, the TUT based platform can be combined with optical cell imaging and manipulation technologies to favor many biomedical applications and help gain insights into the mechanobiology of cells.