Digital microfluidics for automated hanging drop cell spheroid culture

Area of Science:

• Biomedical Engineering
• Cell Biology
• Microfluidics

Background:

• Cell spheroids mimic physiological tissues but their use in research is limited by complex workflows.
• Automating spheroid formation and analysis is crucial for broader adoption in biomedical research.

Purpose of the Study:

• To develop and validate a digital microfluidic platform for automating the formation, maintenance, and analysis of multicellular spheroids.
• To demonstrate the platform's capability in handling cell cultures and performing drug screening assays.

Main Methods:

• A digital microfluidic device was engineered with through-holes for automated liquid handling in hanging drop cultures.
• Mouse mesenchymal stem cell spheroids were formed and maintained for 72 hours.
• A drug screen was conducted on human colorectal adenocarcinoma spheroids.

Main Results:

• The platform successfully formed and maintained mouse mesenchymal stem cell spheroids with high viability (>90%) and uniformity.
• The system demonstrated reproducible results within and between experiments.
• The drug screen successfully recapitulated drug resistance phenomena in human colorectal adenocarcinoma spheroids.

Conclusions:

• The digital microfluidic platform offers an automated, flexible solution for cell spheroid culture and analysis.
• This technology can streamline 3D cell-based assays, facilitating routine use in biomedical research.
• The platform supports in situ sample preparation and analysis, enhancing experimental throughput and reliability.