Machine Learning of Temperature-dependent Chemical Kinetics Using Parallel Droplet Microreactors

摘要

Temperature is a fundamental regulator of chemical and biochemical kinetics, yet capturing nonlinear thermal effects directly from experimental data remains a major challenge due to limited throughput and model flexibility. Recent advances in machine learning have enabled flexible modeling beyond conventional physical laws, but most existing strategies remain confined to surrogate models of end-point yields rather than full kinetic dynamics. Consequently, an end-to-end framework that unifies systematic kinetic data acquisition with machine learning based modeling has been lacking. In this paper, we present a unified framework that integrates droplet microfluidics with machine learning for the systematic analysis of temperature-dependent reaction kinetics. The platform is specifically designed to enable stable immobilization and long-term time-lapse imaging of thousands of droplets under dynamic thermal gradients. This configuration yields massively parallel time-resolved datasets across diverse temperature conditions that capture transient kinetics and provides particularly suitable inputs for training machine-learning models of reaction dynamics. Leveraging these datasets, we train Neural ODE models, which embed neural networks within differential equations to flexibly represent nonlinear temperature dependencies beyond conventional formulations. We demonstrate accurate prediction of enzymatic kinetics across diverse thermal environments, highlighting the robustness and versatility of the approach. Our framework bridges high-throughput experimental data acquisition with data-driven modeling, establishing a versatile foundation for enhanced predictive ability and rational analysis and design of temperature-sensitive biochemical processes.