High-throughput, low-cost reaction screening using a modified 3D printer

Analyst. 2019 Aug 5;144(16):4978-4984. doi: 10.1039/c9an00785g.

Abstract

We describe a reaction screening system, based on a 96-well array, and scaled to suit use on the individual scientist's bench. The system was built by modifying a desktop 3D printer and fitting it with a glass syringe and microtiter plate. The effects of experimental variables were characterized, and the performance of the system was optimized. Precise volumes of reaction mixtures (<3% CV) were dispensed into the 96-well array in ca. 40 minutes. The system was used to screen reagents and solvents for the N-alkylation, Katritzky transamination, and Suzuki cross-coupling reactions. Product distributions derived from electrospray mass spectra and represented as heat maps facilitated recognition of optimum conditions. Screening of 96 reaction mixtures was completed in the modest time of approximately 105 minutes (∼65 seconds per reaction mixture). The system is constructed from open-source software and inexpensive 3D printer hardware.