Long-Term Multiparameter Sensing Integrated On-Chip Ultrasound for Epileptic Neuron Modulation
Yongxu Ju, Xiao Wang, Yang Liu, Chuan Chen, Fang Yang
ACS Sensors 2025 · 10.1021/acssensors.5c00258
Abstract
Ultrasound neuromodulation holds great potential for treating neurological disorders. However, the molecular mechanisms underlying its effects remain unclear. There is a lack of systematic safety evaluation and standardized quantification of therapeutic outcomes. To address these challenges, this study integrates on-chip ultrasound with multiparameter cellular monitoring to quantitatively assess the therapeutic effects of various ultrasound parameters on neurological diseases from both electrophysiological and metabolic perspectives. Long-term monitoring is employed for a comprehensive evaluation of ultrasound safety. Notably, the combination of high-resolution, synchronous signal monitoring and biochemical indicators provides a deeper and more thorough understanding of the molecular mechanisms involved in ultrasound neuromodulation. Furthermore, using an on-chip epileptic neuron model, it is demonstrated that epileptic neurons exhibit high-frequency firing and synchronized oscillations in excitability, temperature, intracellular calcium, and mitochondrial calcium concentrations. The application of on-chip ultrasound effectively suppresses epileptiform discharges in neurons and inhibits both these oscillations and neuronal bursting events. When tuning with acoustic enhancer sodium valproate-loaded nanobubbles, the antiepileptic therapy effect can be significantly enhanced by maintaining mitochondrial calcium homeostasis. By integrating multiparameter long-term monitoring with on-chip ultrasound, this study presents an advanced approach for investigating the mechanisms of ultrasound neuromodulation, facilitating standardized evaluation and long-term safety assessment.
Abstract via europepmc.
Exposures
Exposure 1: On-chip LIPUS (US1-US4) on epileptic cultured neurons
Target: cultured neurons — “on-chip epileptic neurons”
Device: custom-built · interdigital transducer (IDT) microelectrode and platinum resistor array chip
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,000 | ✓✓✓ |
| Pulse duration (ms) | not reported | |
| Pulse repetition frequency (Hz) | not reported | |
| Duty cycle (%) | 30 | ✓✓✓ |
| Sonication duration (s) | 300 | ✓✓✓⚑ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not applicable | |
| In-situ pressure (kPa) | not applicable | |
| In-situ Isppa (W/cm²) | not applicable | |
| In-situ Ispta (W/cm²) | not applicable | |
| Pressure, domain unspecified (kPa) | 30 | ✓?⚑ |
Four LIPUS parameter sets (US1-US4, listed in supplementary Table S1) were applied to Mg2+-free epileptic neuron cultures on a surface acoustic wave chip; 1 MHz, 30 kPa and 30% duty cycle is the parameter set the abstract reports as suppressing discharges; US2 was applied for 5 min in the heating test.
Flags from extraction
species— Species of the cultured neurons not stated in the main text.exposures[0].unspecified_domain.pressure_kpa— Abstract gives 1 MHz, 30 kPa, 30% duty cycle; full US1-US4 parameters are in a supplementary table not in the text.exposures[0].timing.sonication_duration_s— Only a 5 min application for US2 in the heating test is mentioned; protocol otherwise in supplement.