Scalable Multiplexed Drug-Combination Screening Platforms Using 3D Microtumor Model for Precision Medicine

Area of Science:

• Oncology
• Biotechnology
• Pharmacology

Background:

• Cancer heterogeneity necessitates personalized treatment strategies.
• Drug combinations offer enhanced efficacy over single agents but pose screening challenges.
• Current methods for large-scale drug combination screening are complex and costly, especially with limited patient samples.

Purpose of the Study:

• To develop a scalable, high-throughput drug combination screening scheme for cancer.
• To enable efficient testing of numerous pairwise drug combinations with logarithmic concentration ratios.
• To facilitate precision medicine by screening drug combinations on patient-derived cancer cells.

Main Methods:

• Introduction of a "Christmas tree mixer" structure for logarithmic drug concentration ratios.
• Utilization of a three-layer chip design with specialized inlets for simplified drug loading.
• Implementation of an 8-drug combination chip capable of screening 172 conditions across 1032 3D cancer spheroids.

Main Results:

• Demonstrated a scalable and user-friendly high-throughput drug combination screening platform.
• Successfully screened multiple drug combinations on both cancer cell lines and patient-derived cells.
• Validated the potential for comprehensive pairwise drug combination screening with logarithmic mixing ratios.

Conclusions:

• The developed screening scheme significantly reduces experimental complexity and cost for drug combination studies.
• This platform supports precision medicine by enabling efficient and personalized drug combination testing.
• The technology holds promise for accelerating the discovery of effective cancer combination therapies.