Brain Organoids, Lessons from Fetal Neocortex Formation, and Rational Design for Quality Control

Area of Science:

• Neuroscience
• Developmental Biology
• Biotechnology

Background:

• Cerebral organoids are increasingly used to study human-specific neural diseases.
• Inconsistent quality control in organoid studies limits physiological relevance.
• Understanding in vivo neocortex formation is crucial for improving organoid models.

Purpose of the Study:

• To provide a guide for real-time removal of maldeveloped cerebral organoids.
• To present a platform for automated quality control of organoid development.
• To enhance the rigor and reproducibility of cerebral organoid research.

Main Methods:

• Discussion of in vivo neocortex development stages and their recapitulation in organoid protocols.
• Development of a real-time operator removal technique for maldeveloped organoids in shaking culture.
• Preliminary work on an organoid imaging and mesofluidic control platform for automated quality control.

Main Results:

• A practical guide for identifying and removing maldeveloped organoids during culture.
• Demonstration of an imaging and mesofluidic system for automated quality assessment.
• Establishment of a framework for high-throughput, visual quality control of brain organoids.

Conclusions:

• The developed approach significantly improves the morphological assessment of organoids.
• This enhances the physiological relevance and effect sizes in disease etiology studies.
• Paves the way for Good Manufacturing Practice (GMP) compliant cortical organoids in high-throughput applications.