Cell modulation poses an invaluable role in understanding the biophysics, deciphering the neural circuits, and exploring clinical treatment of diseases. Optoacoustic cell modulation is an emerging modality benefiting from the merits of ultrasound with high penetration depth as well as photons with high spatial precision. My thesis work focused on the development of a fiber optoacoustic emitter for neural stimulation and the study of biomolecular mechanisms underlying optoacoustic cell modulation.
To enable region specific and high-efficiency cell modulation, we developed a fiber-based optoacoustic emitter (FOE), serving as a miniaturized ultrasound point source, with sub-millimeter confinement. By modifying acoustic damping and light absorption performance, controllable frequencies in the range of 0.083 MHz to 5.500 MHz are achieved and further induce cell membrane sonoporation with frequency dependent efficiency. These data demonstrate the potential of FOE in region-specific drug delivery, gene transfection and neurostimulation.
To achieve neuromodulation at single cell spatial resolution, we further developed a tapered fiber optoacoustic emitter (TFOE) enabling stimulation of single neurons and subcellular structures. The highly confined ultrasound enabled integration of the optoacoustic stimulation with stable patch clamp recording on single neurons for the first time. Cell-type-specific response of excitatory and inhibitory neurons to acoustic stimulation was unveiled.
Towards understanding the biomolecular mechanisms of optoacoustic cell modulation, we show that optoacoustic excites primary cortical neurons through specific calcium-selective mechanosensitive ion channels with the assistant of calcium amplifier channel and voltage-gated channels. Pharmacological inhibition of specific ion channels leads to reduced responses, while over-expressing these channels results in stronger stimulation. These results shed new insights into the mechanism of ultrasound neurostimulation.
Together, these findings offer a platform for understanding the mechanism of acoustic cell modulation as well as non-genetic, high precision cell modulation method enabling treatment of diseases. / 2025-09-21T00:00:00Z
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/47007 |
| Date | 22 September 2023 |
| Creators | Shi, Linli |
| Contributors | Yang, Chen |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
| Rights | Attribution 4.0 International, http://creativecommons.org/licenses/by/4.0/ |
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