# Multiscale 3D microfluidic platform for intraorganoid delivery

## TL;DR

A new microfluidic platform enables precise delivery of substances into neural organoids, improving their viability and function.

## Contribution

A multiscale 3D microfluidic platform is introduced for controlled intra-organoid delivery with high spatial and temporal precision.

## Key findings

- The platform allows controlled transport of biomolecules to depths of ~400 μm with ~100 μm resolution.
- Delivery of growth factor–supplemented media reduces apoptosis and improves neural tissue integrity.
- The system supports minute-scale temporal precision for delivering dyes, morphogens, and MRI contrast agents.

## Abstract

Neural organoids are emerging as advanced three-dimensional (3D) in vitro models for recapitulating human development and pathology, but they lack dedicated mass-transport pathways that perfuse interior regions, limiting control over solute concentrations in deep tissues. Microfluidic technologies hold promise for intra-organoid delivery, yet creating high-resolution 3D transport architectures spanning arteriole-to-venule scales while integrating them with minimal disruption to morphogenesis remains challenging. Here, we introduce a multiscale 3D microfluidic delivery platform that embeds lithographically defined, flexible, thread-like microchannels into organoids during growth. The nanoporous interface along the embedded microchannels enables controlled diffusive transport of biomolecules into localized regions with ~100 μm spatial resolution and to depths of ~400 μm from the organoid center, with minute-scale temporal precision, as demonstrated with dyes, morphogens, and MRI contrast agents. Delivery of growth factor–supplemented media leads to reduced apoptosis near the microchannels and improved neural tissue integrity. This platform offers a robust means to interrogate deep, site-specific microenvironments and to advance studies of organoid viability, structural organization, and functional maturation.