Focused ultrasound neuromodulation on a multiwell MEA
Marta Saccher, Shinnosuke Kawasaki, Martina Proietti Onori, Geeske M. van Woerden, Vasiliki Giagka, Ronald Dekker
Bioelectronic Medicine 2022 · 10.1186/s42234-021-00083-7
Abstract
Background Microelectrode arrays (MEA) enable the measurement and stimulation of the electrical activity of cultured cells. The integration of other neuromodulation methods will significantly enhance the application range of MEAs to study their effects on neurons. A neuromodulation method that is recently gaining more attention is focused ultrasound neuromodulation (FUS), which has the potential to treat neurological disorders reversibly and precisely. Methods In this work, we present the integration of a focused ultrasound delivery system with a multiwell MEA plate. Results The ultrasound delivery system was characterised by ultrasound pressure measurements, and the integration with the MEA plate was modelled with finite-element simulations of acoustic field parameters. The results of the simulations were validated with experimental visualisation of the ultrasound field with Schlieren imaging. In addition, the system was tested on a murine primary hippocampal neuron culture, showing that ultrasound can influence the activity of the neurons. Conclusions Our system was demonstrated to be suitable for studying the effect of focused ultrasound on neuronal cultures. The system allows reproducible experiments across the wells due to its robustness and simplicity of operation.
Abstract via europepmc.
Exposures
Exposure 1: 5 MHz continuous wave, 15 s and 60 s exposures
Target: cultured neurons — “murine primary hippocampal neuron culture”
Device: Olympus / Panametrics · Olympus Panametrics NTD · V310 ✓
| Waveform | continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 5,000 | ✓✓✓ |
| Pulse duration (ms) | not applicable | |
| Pulse repetition frequency (Hz) | not applicable | |
| Duty cycle (%) | not applicable | ⚑ |
| Sonication duration (s) | 15, 60swept | ✓✓✓ |
| 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 |
Continuous ultrasound at 5 MHz for 15 s or 60 s; each treatment repeated three times with a 5 minute observation period (post period) between treatments; the experiment was performed twice for each protocol.
Flags from extraction
exposures[0].in_situ.pressure_kpa— Simulated (COMSOL) peak pressure at the neuron layer in a dish, including standing-wave reflections from the quartz well bottom; there is no skull or tissue path, so the in_situ block may be better read as the at-target value for a dish. Free-field hydrophone pressure was measured but no value is given in the text.n_subjects— Seven MEA wells; the text does not give the number of cultures or animals. Wells treated as preparations.exposures[0].timing.duty_cycle_pct— Continuous wave; duty cycle not stated.