Janus microparticles-based targeted and spatially-controlled piezoelectric neural stimulation via low-intensity focused ultrasound

基于 Janus 微粒的低强度聚焦超声靶向和空间控制压电神经刺激

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作者:Mertcan Han, Erdost Yildiz, Ugur Bozuyuk, Asli Aydin, Yan Yu, Aarushi Bhargava, Selcan Karaz, Metin Sitti

Abstract

Electrical stimulation is a fundamental tool in studying neural circuits, treating neurological diseases, and advancing regenerative medicine. Injectable, free-standing piezoelectric particle systems have emerged as non-genetic and wireless alternatives for electrode-based tethered stimulation systems. However, achieving cell-specific and high-frequency piezoelectric neural stimulation remains challenging due to high-intensity thresholds, non-specific diffusion, and internalization of particles. Here, we develop cell-sized 20 μm-diameter silica-based piezoelectric magnetic Janus microparticles (PEMPs), enabling clinically-relevant high-frequency neural stimulation of primary neurons under low-intensity focused ultrasound. Owing to its functionally anisotropic design, half of the PEMP acts as a piezoelectric electrode via conjugated barium titanate nanoparticles to induce electrical stimulation, while the nickel-gold nanofilm-coated magnetic half provides spatial and orientational control on neural stimulation via external uniform rotating magnetic fields. Furthermore, surface functionalization with targeting antibodies enables cell-specific binding/targeting and stimulation of dopaminergic neurons. Taking advantage of such functionalities, the PEMP design offers unique features towards wireless neural stimulation for minimally invasive treatment of neurological diseases.

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