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PhD Thesis Proposal: Tomas Jordan

Thursday, June 4, 2020, 10:00am

Videoconference

For info on how to attend this videoconference, please email tomas.jordan.TH@dartmouth.edu

“Minimally Invasive Neural Stimulation Enabled by Piezoelectric Nanoparticles and Ultrasound”

Abstract

Minimally invasive stimulation of select neurons in the brain with great spatio-temporal precision is one of the long-term goals of neuroscience. This work aims to overcome the limitations of established techniques by combining non-invasive focused ultrasound (FUS) and nano-sized transducers bound to the membranes of target neurons. These nanotransducers are piezoelectric barium titanate nanoparticles (BTNPs) that are capable of converting the ultrasound-induced mechanical deformations into localized electric charges via the direct piezoelectric effect. To successfully stimulate neurons using ultrasound activated BTNPs, extensive modifications of the nanoparticles were necessary. First, we enhanced the piezoelectric properties of the BTNPs by electrical poling of the particles in a strong electric field at a high temperature. Second, we performed surface modifications to stabilize the BTNPs in water and physiological media and to enable fluorescent labeling and tuning of the surface charge. Third, we developed a directional antibody conjugation chemistry for attachment of IgG antibodies to the nanoparticle surface, allowing efficient molecular targeting to cells of interest. To demonstrate that neurons can be excited using ultrasound activated BTNPs, we utilized cultured rat hippocampal neurons expressing genetically encoded reporters of calcium and glutamate activity (GCaMP and GluSnFr respectively). We delivered pulses of FUS to neurons with bound BTNPs. Fluorescent imaging of GCaMP confirmed calcium signaling similar to the influx caused by electrical stimulation of the cells. Imaging of GluSnFr activity indicated glutamate release following the FUS stimulus. This release was present when only a small number of BTNPs was bound to the neurons and the response was repeatable a high percentage of the time. However, FUS alone without the BTNPs failed to reliably elicit neural activity. Based on these results, we conclude that ultrasound activated BTNPs show strong potential as a technique for minimally invasive neural stimulation.

Thesis Committee

For more information, contact Daryl Laware at daryl.a.laware@dartmouth.edu.