A Plug-and-Play, Drug-on-Pillar Platform for Combination Drug Screening Implemented by Microfluidic Adaptive Printing

Area of Science:

• Biotechnology
• Pharmacology
• Cancer Research

Background:

• Traditional high-throughput drug screening relies on automated pipetting into microtiter plates, which can be time-consuming and prone to cross-contamination.
• Developing efficient methods for screening drug combinations is crucial for identifying novel cancer therapies.
• Existing methods often lack flexibility in temporally separating drug dispensing and cell-based screening.

Purpose of the Study:

• To introduce and validate a novel drug-on-pillar platform for efficient, high-throughput drug combination screening.
• To demonstrate the plug-and-play capability of the platform, allowing for temporal separation of drug dispensing and cell screening.
• To assess the efficacy of paired drugs against MDA-MB-231 triple-negative human breast cancer cells using the developed platform.

Main Methods:

• Development of a drug-on-pillar platform utilizing a microfluidic pneumatic printing system with low-cost disposable cartridges.
• Integration of a previously developed drug nanoformulation method using amphiphilic telodendrimers for stable dry drug storage.
• Implementation of a 1260-spot drug combination array for screening paired drug effects on cancer cells.

Main Results:

• The drug-on-pillar platform facilitates plug-and-play drug combination screening with temporal separation of dispensing and screening.
• The microfluidic printing platform minimizes cross-contamination, and nanoformulation ensures drug stability for storage and shipping.
• Screening of 1260 drug combinations against MDA-MB-231 cells provided valuable insights into drug combination efficacy for triple-negative breast cancer.

Conclusions:

• The drug-on-pillar platform is a feasible and efficient tool for high-throughput drug combination screening.
• The platform's design allows for temporal and spatial separation of drug handling and cell-based assays, enabling remote laboratory operations.
• This approach offers a promising strategy for discovering effective drug combinations against challenging cancers like triple-negative breast cancer.