Marrying chemistry with biology by combining on-chip solution-based combinatorial synthesis and cellular screening

Area of Science:

• Biotechnology
• Chemical Biology
• Drug Discovery

Background:

• High-throughput screening is crucial for drug development but is hindered by inefficient, separate chemical synthesis and biological testing.
• Current methods are costly and time-consuming due to the incompatibility of synthesis and screening environments.

Purpose of the Study:

• To develop an integrated on-chip platform (chemBIOS) for simultaneous compound synthesis and biological screening.
• To demonstrate the platform's efficiency in synthesizing and screening compound libraries with reduced reagent volumes and time.

Main Methods:

• Developed the chemBIOS platform, enabling parallel solution-based synthesis and biological screening in a single system.
• Utilized the platform for 75 parallel three-component reactions to synthesize lipidoids.
• Performed on-chip characterization (MALDI-MS), lipoplex formation, and cell screening.

Main Results:

• Successfully synthesized a library of 75 lipidoids on-chip.
• Completed the entire process from synthesis to cell screening in just 3 days.
• Required only approximately 1 mL of total solutions for the entire workflow.

Conclusions:

• The chemBIOS platform offers a miniaturized, parallelized, and integrated solution for chemical synthesis and biological screening.
• This technology significantly enhances efficiency and accelerates the drug discovery and development pipeline.