A Microfluidic High-Capacity Screening Platform for Neurological Disorders.

Area of Science:

• Neuroscience
• Microfluidics
• Cell Biology

Background:

• Compartmentalized cell cultures (CCCs) are crucial for studying neurological diseases like Alzheimer's and Parkinson's.
• Existing CCC devices often lack the capacity for high-throughput drug discovery and mechanism identification.

Purpose of the Study:

• To develop a high-capacity, microfluidic plate for parallelized CCCs compliant with ANSI/SLAS standards.
• To enable detailed morphological and functional studies of neuronal cultures for drug discovery.

Main Methods:

• A novel microtiter microfluidic plate with 96 parallel experimental units, each containing three connected compartments.
• Utilized rodent primary and human-induced pluripotent stem cell-derived neurons.
• Immunocytochemistry and electrophysiological recordings to assess neuronal morphology and function.

Main Results:

• The plate design successfully cultured neurons for up to 14 days, restricting soma while allowing axon growth between compartments.
• Demonstrated spontaneous neuronal activity and synaptic coupling between compartments.
• Confirmed compatibility with both central and peripheral nervous system neurons.

Conclusions:

• The developed microfluidic plate significantly increases the capacity for neurological in vitro studies.
• This high-throughput system facilitates the identification of novel mechanisms, drug targets, and therapeutic compounds for neurodegenerative diseases.