Assisted Active Learning for Model-Based Method Development in Liquid Chromatography.

Abstract

In recent decades, there has been a growing interest in fully automated methods for tackling complex optimization problems across various fields. Active learning (AL) and its variant, assisted active learning (AAL), incorporating guidance or assistance from external sources into the learning process, play key roles in this automation by enabling the autonomous selection of optimal experimental conditions to efficiently explore the problem space. These approaches are particularly valuable in situations wherein experimentation is costly or time-consuming. This study explores the application of AAL in model-based method development (MD) for liquid chromatography (LC) by using Bayesian statistics to incorporate historical data and analyte information for the generation of initial retention models. The process involves updating the model parameters based on new experiments, coupled with an active data selection method to choose the most informative experiment to run in a subsequent step. This iterative process balances model exploitation and experimental exploration until a satisfactory separation is achieved. The effectiveness of this approach is demonstrated via two practical examples, resulting in optimized separations in a limited number of experiments by optimizing the gradient slope. It is shown that the ability of AAL to leverage past knowledge and compound information to improve accuracy and reduce experimental runs offers a flexible alternative approach to fixed design methods.