GHz Ultrasound and Electrode Chip-Scale Arrays Stimulate and Influence Morphology of Human Neural Cells.

Abstract

This study describes the effects of chip-scale gigahertz (GHz) ultrasound (US) and electrical stimulus on the morphology, functionality, and viability of neural cells in vitro. The GHz frequency stimulation is achieved using aluminum nitride piezoelectric transducers fabricated on a silicon wafer, operating at 1.47 GHz, corresponding to the film's thickness mode resonance. These devices are used to stimulate SH-SY5Y neural cells in vitro and observe effects on the morphology and viability of the stimulated cells. It is possible to use these devices to deliver either ultrasonic stimulus alone or US stimulus in conjunction with electrical stimulus. Viability tests demonstrated that the neurons retained structural integrity and viability across a wide range of GHz US stimulus intensities (0-1.2 W/cm2), validating that measurements occur at nontoxic doses of US. Neural stimulation is validated with these devices following the outputs of a previous study, with the normalized fluorescence intensity of activated cells between 1.9 and 2.4. The 300-s ultrasonic stimulation at 1.47 GHz and 0.05 W/cm2 peak intensity led to a decrease in nuclear elongation by 17.5% and a cross-sectional area decrease by 17.8% across three independent trials of over 150 cells per category ( ). The F-actin governed cellular elongation increased in length by up to 16.3% in cells exposed to an ultrasonic stimulus or costimulus ( ). Neurite length increased following ultrasonic stimulation compared with control by 75.8% ( ). This article demonstrates new GHz US and electrical chip-scale arrays with apparent effects in both neural excitation and cell morphology.