Abstract
BackgroundMicroelectrode 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.MethodsIn this work, we present the integration of a focused ultrasound delivery system with a multiwell MEA plate.ResultsThe 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.ConclusionsOur 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.
Highlights
Microelectrode arrays (MEA) enable the measurement and stimulation of the electrical activity of cultured cells
Modelling of ultrasound field To estimate the effect of the MEA plate on the ultrasound field, a finite element model was computed in COMSOL (Multiphysics)
The system was characterised by pressure measurements, Schlieren imaging and finite element methods simulations
Summary
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 broad range of ultrasound (US) parameters have been tested, a gap in the research on the effects of high frequency neuromodulation exist, especially concerning which combination of parameters exactly causes excitation or inhibition of the neurons (Blackmore et al 2019). A simpler system to study the effect of ultrasound neuromodulation is to use cultured neurons on a microelectrode array (MEA). This makes it possible to study the effect of different ultrasound parameters on the activity of neurons, as well as using (2022) 8:2 drugs to characterize the mechanism underlying these effects. Significant advancements in human stem cell technology have enabled the quick and efficient generation of human neurons in a dish that could be used to test potential ultrasound treatments to find the optimal solution for a specific patient (Keller and Frega 2019)
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