Controlling cell–cell interactions using surface acoustic waves

Significance We present a unique acoustic well approach that can precisely control cell-to-cell distance and cell–cell interactions. Our technology can achieve high precision and high throughput simultaneously while preserving the integrity of cells. It is capable of creating cell assemblies with precise spatial control both in suspension and on a substrate. We envision the exploitation of this powerful technology, for example, in the study of cell–cell interactions in fields, such as immunology, developmental biology, neuroscience, and cancer metastasis, and in the studies of cell–cell and cell–matrix adhesion. The interactions between pairs of cells and within multicellular assemblies are critical to many biological processes such as intercellular communication, tissue and organ formation, immunological reactions, and cancer metastasis. The ability to precisely control the position of cells relative to one another and within larger cellular assemblies will enable the investigation and characterization of phenomena not currently accessible by conventional in vitro methods. We present a versatile surface acoustic wave technique that is capable of controlling the intercellular distance and spatial arrangement of cells with micrometer level resolution. This technique is, to our knowledge, among the first of its kind to marry high precision and high throughput into a single extremely versatile and wholly biocompatible technology. We demonstrated the capabilities of the system to precisely control intercellular distance, assemble cells with defined geometries, maintain cellular assemblies in suspension, and translate these suspended assemblies to adherent states, all in a contactless, biocompatible manner. As an example of the power of this system, this technology was used to quantitatively investigate the gap junctional intercellular communication in several homotypic and heterotypic populations by visualizing the transfer of fluorescent dye between cells.