A high-throughput, open-space and reusable microfluidic chip for combinational drug screening on tumor spheroids

Area of Science:

• Biotechnology
• Microfluidics
• Oncology

Background:

• Current drug combination screening is limited to binary or gradient approaches.
• Complex therapeutic strategies require systematic evaluation of multiple agents.
• Tumor spheroids are valuable models for disease treatment and personalized medicine.

Purpose of the Study:

• To develop a high-throughput microfluidic chip for screening complex drug combinations on tumor spheroids.
• To enable systematic investigation of multiple factors influencing tumor spheroid growth and response.
• To advance personalized medicine through efficient drug discovery.

Main Methods:

• Fabrication of a multilayered, open-space microfluidic chip using polymethyl methacrylate (PMMA).
• Integration of design-of-experiment (DOE) principles for generating diverse drug combinations.
• Utilized a HeLa reporter cell line to quantify spheroid autophagy and growth dynamics.
• Tested combinations of L-glutamine, D-glucose, FBS, and cisplatin.

Main Results:

• The microfluidic chip demonstrated quantitative agreement with DOE principles.
• D-glucose was found to inhibit the effects of cisplatin on tumor spheroids.
• Cisplatin induced significant autophagy in 3D tumor spheroids, more so than in 2D cultures.

Conclusions:

• The developed microfluidic chip facilitates high-throughput screening of complex drug combinations.
• This technology can be extended to DOE with seven or more inputs, enabling broader therapeutic exploration.
• The findings provide insights into drug interactions and spheroid response for cancer treatment development.