Highly parallel optimisation of chemical reactions through automation and machine intelligence

Abstract We report the development and application of a scalable machine learning (ML) framework (Minerva) for highly parallel multi-objective reaction optimisation with automated high-throughput experimentation (HTE). Minerva demonstrates robust performance with experimental data-derived benchmarks...

Full description

Saved in:
Bibliographic Details
Main Authors: Joshua W. Sin, Siu Lun Chau, Ryan P. Burwood, Kurt Püntener, Raphael Bigler, Philippe Schwaller
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-61803-0
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract We report the development and application of a scalable machine learning (ML) framework (Minerva) for highly parallel multi-objective reaction optimisation with automated high-throughput experimentation (HTE). Minerva demonstrates robust performance with experimental data-derived benchmarks, efficiently handling large parallel batches, high-dimensional search spaces, reaction noise, and batch constraints present in real-world laboratories. Validating our approach experimentally, we apply Minerva in a 96-well HTE reaction optimisation campaign for a nickel-catalysed Suzuki reaction, tackling challenges in non-precious metal catalysis. Our approach effectively navigates the complex reaction landscape with unexpected chemical reactivity, outperforming traditional experimentalist-driven methods. Extending to industrial applications, we deploy Minerva in pharmaceutical process development, successfully optimising two active pharmaceutical ingredient (API) syntheses. For both a Ni-catalysed Suzuki coupling and a Pd-catalysed Buchwald-Hartwig reaction, our approach identifies multiple conditions achieving >95 area percent (AP) yield and selectivity, directly translating to improved process conditions at scale.
ISSN:2041-1723