Perfused drop microfluidic device for brain slice culture-based drug discovery

Area of Science:

• Neuroscience
• Microfluidics
• Biotechnology

Background:

• Organotypic brain slice cultures are vital for in vitro modeling of brain functions.
• Current methods face limitations in achieving high parallelism, throughput, and long-term recordings for complex disease modeling.
• There is a need for advanced platforms to support extensive neurophysiology, pharmacology, and toxicology studies.

Purpose of the Study:

• To develop and validate a novel perfused drop microfluidic device for long-term organotypic brain slice cultures.
• To enable high-throughput and long-term electrical recordings from multiple brain slice cultures simultaneously.
• To facilitate advanced applications in drug discovery and toxicology research.

Main Methods:

• Development of a polydimethylsiloxane (PDMS) microfluidic device featuring a perfused drop system.
• Hydrostatic control of fluid levels to form drops around brain slices within wells.
• Continuous perfusion of culture medium through microchannels to maintain slice viability.
• Integration of the microfluidic device with substrate-printed microelectrodes for multi-electrode array (MEA) recordings.

Main Results:

• Viable organotypic hippocampal slice cultures were successfully maintained for at least 9 days in vitro.
• The device demonstrated the capability for long-term culture maintenance and perfusion.
• Successful integration with MEA chips allowed for parallel electrical recordings from multiple cultures.
• The system supports high parallelism and throughput for electrophysiological studies.

Conclusions:

• The novel perfused drop microfluidic device supports long-term viability of organotypic brain slice cultures.
• This scalable platform facilitates high-throughput parallel electrical recordings.
• The technology is expected to significantly advance drug discovery and toxicology screening.