SBIR Phase I: Drug Discovery meets Moore's Law: Synthesizing DNA-Encoded Libraries with Electronics

The broader impact of this Small Business Innovation Research (SBIR) Phase I project is to accelerate drug discovery. Despite massive investment, the pace of drug development is slow and appears to be slowing further, with new drugs taking an average of 15-years from discovery to market approval. This project aims to develop hardware that will permit the rapid and inexpensive synthesis of DNA-encoded libraries (DELs).

This will not only expedite finding drugs for challenging diseases but also generate valuable data for training artificial intelligence (AI) models to improve drug prediction. Commercially, this technology will strengthen U.S. competitiveness in drug discovery and reinforce its leadership in automation and AI research. It could also aid in biodefense, enabling faster responses to emerging biological and chemical threats.

The proposed project straddles three different disciplines – electronics, chemistry, and material science – requiring specialized knowledge and expertise in each. Electronics have come to dominate our world as an information processing technology. Its function is to manipulate voltage values, representing the 1's and 0's encoding data.

This project proposes a means of chemical processing with electronics. The goal is to build a device that can perform combinatorial chemistry on nanoliter to picoliter volume droplets, on an electronic substrate. This will be applied to the task of synthesizing DELs.

Unlike liquid-handling robots, the technology has no moving or mechanical parts. Instead, it manipulates droplets with electric charge. Software controls the switching of the voltages on a grid of electrodes, dispensing, moving, splitting, merging, and mixing droplets.

The research addresses key technical challenges, including the durability of dielectric and hydrophobic materials, and optimizing electric field control. The chemical protocols for synthesizing DELs will be adapted to novel physical and chemical constraints, including very small volumes. Mitigating contamination is a significant technical risk, requiring innovations in the design, material science, and chemical protocols.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.