2024 | Mertcan Han, Erdost Yildiz, Ugur Bozuyuk, Asli Aydin, Yan Yu, Aarushi Bhargava, Selcan Karaz & Metin Sitti
This study presents a novel approach for targeted and spatially-controlled piezoelectric neural stimulation using Janus microparticles (PEMPs) under low-intensity focused ultrasound (LIFU). PEMPs are 20 μm-diameter silica-based particles with a piezoelectric barium titanate (BTNP) nanoparticle-coated half and a magnetically-responsive nickel-gold nanofilm-coated half. The BTNP-coated half generates electrical stimulation, while the magnetic half enables spatial and orientational control via external magnetic fields. Surface functionalization with targeting antibodies allows cell-specific stimulation of dopaminergic neurons. PEMPs offer a non-genetic, wireless, and minimally invasive alternative to traditional electrode-based systems. They enable high-frequency (up to 200 Hz) neural stimulation with low-intensity ultrasound (threshold <100 mW·cm⁻²), precise spatial control, and cell-specific targeting. In vitro experiments demonstrated that PEMPs can stimulate primary neurons with high success rates (up to 69%) under LIFU, with minimal side effects. The study also evaluated the biocompatibility of PEMPs on various cell types, including SH-SY5Y neurons, astrocytes, and microglia, showing no significant toxicity or immune response. The results indicate that PEMPs have potential for safe and long-term neural stimulation applications in basic neuroscience research and neurotherapeutic treatments. The study highlights the advantages of PEMPs in achieving high spatiotemporal resolution and on-demand control for neural stimulation.This study presents a novel approach for targeted and spatially-controlled piezoelectric neural stimulation using Janus microparticles (PEMPs) under low-intensity focused ultrasound (LIFU). PEMPs are 20 μm-diameter silica-based particles with a piezoelectric barium titanate (BTNP) nanoparticle-coated half and a magnetically-responsive nickel-gold nanofilm-coated half. The BTNP-coated half generates electrical stimulation, while the magnetic half enables spatial and orientational control via external magnetic fields. Surface functionalization with targeting antibodies allows cell-specific stimulation of dopaminergic neurons. PEMPs offer a non-genetic, wireless, and minimally invasive alternative to traditional electrode-based systems. They enable high-frequency (up to 200 Hz) neural stimulation with low-intensity ultrasound (threshold <100 mW·cm⁻²), precise spatial control, and cell-specific targeting. In vitro experiments demonstrated that PEMPs can stimulate primary neurons with high success rates (up to 69%) under LIFU, with minimal side effects. The study also evaluated the biocompatibility of PEMPs on various cell types, including SH-SY5Y neurons, astrocytes, and microglia, showing no significant toxicity or immune response. The results indicate that PEMPs have potential for safe and long-term neural stimulation applications in basic neuroscience research and neurotherapeutic treatments. The study highlights the advantages of PEMPs in achieving high spatiotemporal resolution and on-demand control for neural stimulation.