Multiscale 3D microfluidic platform for intraorganoid delivery

Area of Science:

• Neuroscience
• Bioengineering
• Developmental Biology

Background:

• Neural organoids are valuable 3D models for studying human development and disease.
• Current neural organoids lack efficient internal transport systems, limiting nutrient and oxygen diffusion to deep tissues.
• Microfluidic systems offer potential for precise delivery but integrating them into organoids without disrupting growth is difficult.

Purpose of the Study:

• To develop a multiscale 3D microfluidic platform for controlled intra-organoid delivery.
• To overcome limitations in perfusing deep regions of neural organoids.
• To enable site-specific interrogation of organoid microenvironments.

Main Methods:

• Embedding lithographically defined, thread-like microchannels into growing neural organoids.
• Utilizing a nanoporous interface for controlled diffusive transport.
• Demonstrating delivery of dyes, morphogens, and MRI contrast agents with high spatial and temporal precision.

Main Results:

• Achieved controlled diffusive transport of biomolecules with ~100 um spatial resolution and ~400 um depth.
• Demonstrated minute-scale temporal precision for delivery.
• Observed reduced apoptosis and improved neural tissue integrity with growth factor delivery.

Conclusions:

• The developed platform enables precise, site-specific delivery within neural organoids.
• This technology enhances organoid viability and structural organization.
• It provides a robust tool for advancing research on organoid microenvironments, maturation, and disease modeling.