Rapid Planning and Analysis of High-Throughput Experiment Arrays for Reaction Discovery

Abstract

High throughput experimentation (HTE) is an increasingly important tool in reaction discovery. While the hardware for running HTE in the chemical laboratory has evolved significantly in recent years, there remains a need for software solutions to navigate data-rich experiments. Here we have developed phactor™, a software that facilitates the performance and analysis of HTE in a chemical laboratory. phactor™ allows experimentalists to rapidly design arrays of chemical reactions or direct-to-biology experiments in 24, 96, 384, or 1,536 wellplates. Users can access online reagent data, such as a chemical inventory, to virtually populate wells with experiments and produce instructions to perform the reaction array manually, or with the assistance of a liquid handling robot. After completion of the reaction array, analytical results can be uploaded for facile evaluation, and to guide the next series of experiments. All chemical data, metadata, and results are stored in machine-readable formats that are readily translatable to various software formats. We also demonstrate the use of phactor™ in the discovery of several chemistries, including a light-enabled reagent-free sp2–sp2 deaminative–decarboxylative carbon–carbon coupling and a low micromolar inhibitor of the SARS-CoV-2 main protease. Furthermore, phactor™ has been made available for free academic use in 24 and 96 well formats via an online interface.

Top 20 Influential AI-Based Technologies in Chemistry

“…High-throughput experimentation (HTE) is a methodological approach that leverages robotics, automation, and artificial intelligence (AI) to conduct a large number of chemical experiments simultaneously and rapidly. [106][107][108][109][110][111] This approach is useful for research processes, enabling scientists to explore vast chemical spaces and reaction conditions in a fraction of the time required by https://doi.org/10.26434/chemrxiv-2024-cdm8w ORCID: https://orcid.org/0000-0002-6447-557X Content not peer-reviewed by ChemRxiv. License: CC BY-NC 4.0 traditional methods.…”

Rapid planning and analysis of high-throughput experiment arrays for reaction discovery

“…All relevant interfacing scripts generated in this study have been deposited in an online GitHub repository 68 . https://github.com/ cernaklab/public-phactor-example-files.…”

Organopalladium Catalysis as a Proving Ground for Data-Rich Approaches to Reaction Development and Quantitative Predictions

“…83 In academia, the Cernak group is continuing to push the envelope of ultra-high throughput methods in array design and execution. [84][85][86] In the area of laboratory automation, the Hein group, in collaboration with Merck and the Aspuru-Guzik and Sigman groups, demonstrated the power of data-dense experimentation in an autonomous optimization of a Pd-catalyzed Suzuki-Miyaura reaction. 18 The Newman group published a user-centered "how-to-HTE" guide on multiwell screening, using a Pd-catalyzed C-N coupling as the prototype reaction.…”