co9b00207_si_001.pdf (2.94 MB)
Design of an Automated Reagent-Dispensing System for Reaction Screening and Validation with DNA-Tagged Substrates
journal contribution
posted on 2020-02-27, 16:41 authored by Jens Bobers, Mateja Klika Škopić, Robin Dinter, Piriyanth Sakthithasan, Laura Neukirch, Christian Gramse, Ralf Weberskirch, Andreas Brunschweiger, Norbert KockmannLaboratory
automation strategies have vast potential for accelerating discovery
processes. They enable higher efficiency and throughput for time-consuming
screening procedures and reduce error-prone manual steps. Automating
repetitive procedures can for instance support chemists in optimizing
chemical reactions. Particularly, the technology of DNA-encoded libraries
(DELs) may benefit from automation techniques, since translation of
chemical reactions to DNA-tagged reactants often requires screening
of multiple reaction parameters and evaluation of large numbers of
reactants. Here, we describe a portable, automated system for reagent
dispensing that was designed from open source materials. The system
was validated by performing amide coupling of carboxylic acids to
DNA-linked amine and a micelle-mediated Povarov reaction to DNA-tagged
hexahydropyrroloquinolines. The latter reaction required accurate
pipetting of multiple components including different solvents and
a surface-active reagent. Analysis of reactions demonstrated that
the robotic system achieved high accuracy comparable to experimentation
by an experienced chemist with the potential of higher throughput.