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Highly parallel optimisation of chemical reactions through automation and machine intelligence

Sin, Joshua W.
•
Chau, Siu Lun
•
Burwood, Ryan P.
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December 1, 2025
Nature Communications

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.

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10.1038_s41467-025-61803-0.pdf

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Published version

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openaccess

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CC BY

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