Uncertainty-Aware Machine Learning for Small-Angle X‑ray Scattering Analysis in Autonomous Experimentation

Small-angle X-ray scattering (SAXS) is a powerful high-throughput characterization tool for probing nanoscale structure in native sample environments, providing real-time morphological information such as nanoparticle size and shape during synthesis. However, automated SAXS data analysis for extracting meaningful structural parameters is non-trivial and remains a bottleneck in closed-loop experimentation towards autonomous materials discovery, which demands fast, reliable, and uncertainty-aware data analysis. Here, we develop a machine-learning approach for automated SAXS analysis tailored to closed-loop nanoparticle synthesis. A Random Forest (RF) regression model is trained on 100,000 synthetic SAXS curves generated from polydisperse spherical nanoparticles with realistic background contributions. Using normalized one-dimensional SAXS intensity profiles as input, the RF model directly predicts nanoparticle radius, size polydispersity, and background parameters, while the ensemble standard deviation across trees provides built-in uncertainty quantification (UQ). On synthetic data, we show that combining fit-quality metrics (R², MAE) with thresholds on prediction uncertainty reliably identifies accurate parameter estimates without access to ground truth. We then apply the trained model to 365 experimental SAXS profiles of citrate-reduced gold nanoparticles synthesized using an automated droplet-flow microreactor with in situ SAXS at a synchrotron beamline, classifying the results into high- and low-confidence subsets based on UQ metrics. Finally, we integrate RF-based SAXS analysis into a simulated closed-loop optimization campaign using Gaussian process Bayesian optimization to minimize nanoparticle polydispersity, benchmarking against conventional automated Levenberg-Marquardt fitting. The RF-guided campaign exhibits substantially faster convergence and lower relative opportunity cost (∼0.07 vs ∼0.3), demonstrating that uncertainty-aware machine-learning SAXS analysis significantly enhances the efficiency and robustness of autonomous nanomaterials synthesis workflows.