Encapsulated droplet array for intensified micromole-scale high-throughput reaction screening

Area of Science:

• Chemical Engineering
• Materials Science
• Synthetic Chemistry

Background:

• Automated high-throughput experimentation (HTE) accelerates chemical reaction discovery.
• Current HTE methods like microwell plates and flow systems have limitations in handling harsh conditions and parallel screening.

Purpose of the Study:

• To introduce a new encapsulated droplet array (EDA) technology for HTE.
• To overcome the limitations of existing HTE platforms for reactions under demanding conditions.

Main Methods:

• Developed an encapsulated droplet array (EDA) with chemically inert pockets and an aluminum chassis.
• Executed microliter-scale reactions within the EDA under elevated temperatures (up to 105°C) and pressures (up to 7 atm).
• Demonstrated versatility across multiple bond-forming reactions including S_NAr, Buchwald-Hartwig amination, and Suzuki-Miyaura coupling.

Main Results:

• The EDA technology supports massively parallel screening of 48 reactions simultaneously.
• Successfully performed various challenging bond-forming reactions under harsh conditions.
• Developed a fully automated platform for end-to-end reaction workflow integration.

Conclusions:

• The EDA technology offers a robust and versatile platform for HTE under demanding conditions.
• This innovation expands the scope of reactions amenable to automated screening.
• The seamless integration with liquid-handling systems enhances experimental efficiency and throughput.