Autonomous Structural Discovery Of Bioprocess Dynamics And Kinetics Via LLM-Driven Agents

Kinetic model discovery is a central challenge in chemical engineering, as accurate rate expressions are essential for understanding and controlling chemical and biological processes. Symbolic regression (SR) has emerged as a powerful data-driven approach for identifying interpretable kinetic models, but usually operates without domain knowledge, often exploring physicochemically implausible models. Large language models (LLMs) offer a promising avenue for injecting domain expertise into this search. Here, we introduce an LLM-guided SR framework, embedding an LLM module within an iterative SR algorithm for automated kinetic model discovery. The LLM performs two roles at each iteration: (1) a qualitative physicochemical critique of the best SR candidates, and (2) the proposal of new candidate rate expressions guided by the SR-generated models and embedded chemical knowledge. Our framework is evaluated on four in silico case studies of increasing complexity, spanning heterogeneous catalysis and bioprocess systems. Results show the LLM-guided framework reduces iterations to identify the ground-truth model by $41.7-79.3\%$ versus a state-of-the-art SR framework, with the LLM directly proposing the correct model structure in over half of the guided runs. In practical settings, where each iteration typically requires a new wet-lab experiment, this translates into a substantial reduction in experimental effort. Predictive performance on an independent validation set is equivalent between both approaches, with $R^2>0.98$ in all case studies. Ablation studies indicate that both the SR component and the LLM scale contribute to this performance, with a reduced-size LLM largely retaining discovery efficiency. These findings demonstrate that LLMs can effectively inject domain knowledge into scientific model discovery, paving the way toward fully automated, domain-aware kinetic modelling pipelines.

Automatic scientific discovery has long been a goal of computational scholars - a machine that can discover nature's secrets on its own, moving computational systems beyond data-fitting tools toward the generation and refinement of mechanistic models of the universe. Recent advances in symbolic regression (SR) and large-language-model (LLM)-based agents suggest that such systems can recover equations from data, incorporate domain priors, and automate parts of the research workflow. However, most existing approaches either focus on narrow equation-discovery benchmarks or broad end-to-end automation pipelines, while biological systems remain comparatively underexplored. Here, we introduce the MEDA system, an LLM- and SR-powered agentic framework for discovering ordinary-differential-equation (ODE) models of biological and biologically inspired dynamical systems. MEDA retrieves background knowledge, defines admissible variables, generates mechanistic constraints, proposes candidate ODEs, and fits and evaluates them. We evaluate it across canonical model retrieval, reasoning-based extrapolation to unseen variants, and open-ended discovery, with and without experimental data. Across these settings, MEDA recovered the correct state variables, achieved strong structural recovery in retrieval and extrapolation tasks, and produced biologically plausible discovery-oriented models. Ablation and robustness analyses show that knowledge-guided formalization and mechanistic constraints are load-bearing components, whereas numerical fitting alone can preserve trajectory-compatible but biologically incorrect equations.

Large language model agents are being increasingly deployed as autonomous scientists, designing experiments and inferring mechanistic world models with minimal human oversight. Yet identifiability is often overlooked: when a plateau is reached, the agent needs to know whether it is not yet capable enough or the model simply is not identifiable from the data, in which case no amount of further experimentation of the same kind can help. We propose the Identifiability-Driven Experimental Agent (LLM-IDEA) for closed-loop discovery with an identifiability engine that returns a three-way plateau verdict: capability limit, resolvable within the design class, or certified exhausted. On ODEBench, 60 of the 62 systems with free constants are identifiable at round 0; the RC circuit is certified exhausted for every experiment that protocol can run, and a harvesting model is resolvable by one added initial condition. The identifiability engine reproduces known verdicts on Lotka-Volterra, Van der Pol, Lorenz, and a pharmacokinetic model, where it recommends the intravenous arm pharmacologists use, and it ranks the depth scorer of our own benchmark last among four observation designs. On the DiscoverPhysics benchmark, it finds two public worlds whose explanation rubric rewards a distinction no legal experiment can make, and every model there with accurate trajectories failed the explanation grade (15 of 15, against 5 of 9 in identifiable worlds, p = 0.012). On the Alien Universe, a two-body testbed we propose in which a force law switches between a provably non-identifiable and an identifiable protocol, LLM-IDEA on the identifiable protocol reaches discovery depth at least three on 8/8 seeds versus 1/8 without it. An autonomous discovery agent can thus compute, rather than guess, whether a plateau calls for more search, a better experiment of the same kind, or a different kind of experiment.