Sonogenetics: Non-invasive cellular manipulation using ultrasound

Abstract

Optogenetics has been an important tool used in manipulating different cell types, understanding various diseases and has recently been studied as an alternative to electrical manipulation techniques used in a clinical setting. It has the drawback of being an invasive cellular manipulation technique, which limits its applications. Ultrasound is an alternative, non-invasive approach to precisely control cellular function. We propose the development of ultrasound transducers to selectively manipulate cells that have been transfected with mechanically sensitive proteins, in a new technique termed “Sonogenetics.” This study describes recent results in single crystal piezoelectric transducer design and characterization, results from in-vitro studies to identify mechanosensitive proteins, and an in-vivo study where miniature head mounted transducers were used to stimulate the ventral tegmental area of the mouse in order to trigger dopamine release. Ultrasound based stimulation offers superior spatial and temporal control compared to other cellular manipulation techniques. This study enabled development of the tools required for achieving sonogenetic manipulation of cells by presenting novel transducer designs and identification of relevant parameters in order to achieve stimulation of transfected cells.