A multimodal 3D neuro-microphysiological system with neurite-trapping microelectrodes.

Area of Science:

• Neuroscience
• Biotechnology
• Bioengineering

Background:

• Three-dimensional (3D) cell technologies are advancing pre-clinical models for nervous system research.
• Accurate phenotype exploration in engineered 3D neuronal cultures requires comprehensive morphological, molecular, and functional measurements.
• Measuring individual neuron electrical activity with millisecond resolution is critical but challenging with current methods.

Purpose of the Study:

• To develop a novel, high-throughput method for non-invasive electrical recording from 3D neuronal cultures.
• To enable parallelized functional, morphological, and molecular analyses of engineered neuronal models.
• To facilitate high-content screening for neurological disease research and therapeutic compound evaluation.

Main Methods:

• Development and application of multiwell glass microfluidic microelectrode arrays for non-invasive electrical recording.
• Integration of electrophysiology with calcium imaging and optogenetic stimulation.
• Utilizing microplate compatibility for automated handling and high-content analysis of human induced pluripotent stem cell-derived neurons.

Main Results:

• Demonstrated parallelized studies on engineered 3D neuronal cultures using reference compounds.
• Successfully integrated electrical recording with calcium imaging and optogenetic stimulation.
• Showcased automated, high-content analysis capabilities for human induced pluripotent stem cell-derived neurons.

Conclusions:

• The novel microphysiological platform provides a powerful tool for high-throughput studies of neurological diseases.
• This approach allows for detailed investigation of functional, morphological, and molecular aspects of neuronal function.
• Opens new avenues for evaluating potential therapeutic compounds in complex 3D neuronal models.