A microfluidic gradient device for drug screening with human iPSC-derived motoneurons

Area of Science:

• Biomedical Engineering
• Neuroscience
• Stem Cell Technology

Background:

• Neurological diseases require effective drug screening methods.
• Human induced pluripotent stem cell (hiPSC)-derived motoneurons offer a relevant model for studying neuronal function and drug responses.
• Microfluidic devices enable precise control over cellular microenvironments.

Purpose of the Study:

• To develop and validate a microfluidic gradient device for drug screening.
• To assess the utility of the device using hiPSC-derived motoneurons.
• To investigate drug-induced neurite network formation in a controlled gradient environment.

Main Methods:

• An asymmetrically designed microfluidic channel was fabricated to generate concentration gradients.
• A micropillar array was incorporated to trap and culture motoneuron spheroids for 9 days.
• Computational fluid dynamics (CFD) modeling was used to optimize gradient generation.
• Riluzole was used as a test drug to induce neurite outgrowth.

Main Results:

• The microfluidic device successfully generated stable concentration gradients.
• Motoneuron spheroids were cultured and maintained within the device for 9 days.
• A significant motoneuron spheroid-derived neurite network formed in response to riluzole gradients.

Conclusions:

• The developed microfluidic gradient device is a viable platform for drug screening in neurological disease research.
• This system allows for the observation of drug effects on hiPSC-derived motoneuron neurite networks.
• The device holds potential for screening various therapeutic compounds for neurological applications.