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

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.

Curved and Annular Diaphragm Coupled Piezoelectric Micromachined Ultrasonic Transducers for High Transmit Biomedical Applications

“…Specifically, the bandwidth is decreased by a factor of 10 compared to a single curved pMUT and by approximately 50 compared to a single annular pMUT. However, the main purpose of the study is to enhance the transmit efficiency not the bandwidth, which is the dominant obstacle in the applications using continuous waves or modulated waves such as therapy [4,5], biomedical particle manipulation [6][7][8], and neural stimulation [10]. Moreover, we would like to address the possibility of enlarging the bandwidth for the CAC-pMUT array, which is important for medical imaging [1-3] and gesture recognition [9] applications.…”

“…The volumetric displacement resulting from the vibration of the annular pMUT can also be expressed as a function of the incident pressure and the excitation voltage as shown in Equation (10), where the mechanical admittance can be expressed as the volumetric displacement generated by per unit of incident sound pressure, and the electromechanical transduction ratio can be expressed as the volumetric displacement produced per unit voltage [34]:…”

“…In the past decades, ultrasonic transducers have gained increasing popularity in applications such as medical imaging [1][2][3], invasive or non-invasive therapy [4,5], biomedical particle manipulation [6][7][8], gesture recognition [9], and neural stimulation [10]. The high transmit performance of the transducers is key for these applications to achieve enhanced pressure output with good signal-to-noise contrast (SNC).…”