Three-dimensional liquid metal-based neuro-interfaces for human hippocampal organoids

Area of Science:

• Neuroscience
• Stem Cell Biology
• Bioengineering

Background:

• Human hippocampal organoids (hHOs) from human induced pluripotent stem cells (hiPSCs) are valuable models for studying neurodegenerative diseases like Alzheimer's and schizophrenia.
• Current methods using commercial multi-electrode arrays (MEAs) struggle to non-invasively acquire electrical information from free-floating 3D organoids.
• Existing 3D MEAs have limited channel counts, restricting the neural signals that can be captured.

Purpose of the Study:

• To develop a novel platform for non-invasive electrophysiological recording from 3D human hippocampal organoids.
• To create a 'cyborg organoid' by integrating a flexible neuro-interface with hHOs.
• To enable detailed investigation of neural activity and development in complex brain organoid models.

Main Methods:

• Development of a hippocampal cyborg organoid (cyb-organoid) platform.
• Integration of a liquid metal-polymer conductor (MPC)-based mesh neuro-interface (mMPC) with hHOs.
• The mMPC features 128-channel multielectrode arrays with high stretchability and flexibility.
• Induction of hHOs using Wnt3a and SHH activators to generate specific progenitor and neuronal populations (HOPX+, PAX6+, ZBTB20+, PROX1+).

Main Results:

• Successfully created a flexible, stretchable 128-channel mMPC neuro-interface.
• Demonstrated successful attachment of the mMPC to hHOs, forming a cyb-organoid.
• Confirmed hHOs differentiation into HOPX+, PAX6+ progenitors and ZBTB20+, PROX1+ dentate gyrus granule neurons.
• Achieved non-invasive detection of neural activities from hHOs using the mMPC platform.
• Transcriptomic analysis showed high similarity between hHOs and the developing human hippocampus.

Conclusions:

• The developed cyb-organoid platform with an mMPC neuro-interface provides a novel, non-invasive method for recording neural signals from 3D brain organoids.
• This approach overcomes limitations of traditional planar devices and offers enhanced capabilities for studying complex neural circuits in vitro.
• The platform facilitates advanced research into neurological disorders using sophisticated organoid models.